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pubs.acs.org/CR                                                                                                                                  Review



Chiral Induced Spin Selectivity
Brian P. Bloom,* Yossi Paltiel,* Ron Naaman,* and David H. Waldeck*

      Cite This: Chem. Rev. 2024, 124, 1950−1991                                      Read Online


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ABSTRACT: Since the initial landmark study on the chiral induced spin selectivity (CISS)
effect in 1999, considerable experimental and theoretical efforts have been made to




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understand the physical underpinnings and mechanistic features of this interesting
phenomenon. As first formulated, the CISS effect refers to the innate ability of chiral
materials to act as spin filters for electron transport; however, more recent experiments
demonstrate that displacement currents arising from charge polarization of chiral molecules
lead to spin polarization without the need for net charge flow. With its identification of a
fundamental connection between chiral symmetry and electron spin in molecules and
materials, CISS promises profound and ubiquitous implications for existing technologies and
new approaches to answering age old questions, such as the homochiral nature of life. This
review begins with a discussion of the different methods for measuring CISS and then
provides a comprehensive overview of molecules and materials known to exhibit CISS-based
phenomena before proceeding to identify structure−property relations and to delineate the
leading theoretical models for the CISS effect. Next, it identifies some implications of CISS
in physics, chemistry, and biology. The discussion ends with a critical assessment of the CISS field and some comments on its future
outlook.


CONTENTS                                                                                2.4.4. Spin Seebeck Effect                                   1958
                                                                                 3. Materials and Molecules Exhibiting CISS                          1959
1. Introduction                                                    1951              3.1. Molecules and Macromolecules                               1959
2. Methods for Measuring CISS                                      1952                 3.1.1. DNA and Oligopeptides                                 1959
    2.1. Photoelectron Spectroscopy                                1952                 3.1.2. Helicenes                                             1959
       2.1.1. Mott Polarimetry                                     1952                 3.1.3. Proteins                                              1959
       2.1.2. Ultraviolet Photoelectron Spectroscopy               1953                 3.1.4. Polymers                                              1960
    2.2. Electron Transport                                        1953              3.2. Inorganic and Hybrid Organic−Inorganic
       2.2.1. Conductive Probe Atomic Force Micros-                                       Materials                                                  1960
              copy                                                 1953                 3.2.1. Chiral Supramolecular Constructs                      1960
       2.2.2. Scanning Tunneling Microscopy Meth-                                       3.2.2. Chiral Inorganic Nanoparticles                        1960
              ods                                                  1954                 3.2.3. Hybrid Organic Inorganic Perovskites
       2.2.3. Magnetoresistance and Spin Valve Stud-                                           and Metal Halides                                     1961
              ies                                                  1954                 3.2.4. Transition Metal Dichalcogenides
       2.2.4. Electrochemical Tunnel Junctions                     1954                         (TMDs)                                               1961
       2.2.5. Hanle Rotation                                       1955                 3.2.5. Metal Oxides                                          1961
    2.3. Charge Polarization and Spin Polarization                                      3.2.6. Bulk Crystals and Organometallic Con-
         Methods                                                   1955                        structs                                               1962
       2.3.1. Spin-Dependent Polarization in Hall                                    3.3. Summary                                                    1963
              Voltage                                              1955          4. General Trends and Structure−Property Relation-
       2.3.2. Emergent Magnetic Properties and                                      ships                                                            1963
               Magnetic Force Microscopy                           1956
       2.3.3. Spin Exchange Microscopy                             1956
       2.3.4. Kelvin Probe Force Microscopy                        1956          Received: September 13, 2023
    2.4. Other Techniques                                          1957          Revised: January 16, 2024
       2.4.1. Fluorescence                                         1957          Accepted: January 23, 2024
       2.4.2. Resonance Spectroscopies                             1957          Published: February 16, 2024
       2.4.3. Magnetometry and Magneto-optical
              Methods                                              1958

                                       © 2024 The Authors. Published by
                                             American Chemical Society                                            https://doi.org/10.1021/acs.chemrev.3c00661
                                                                          1950                                                Chem. Rev. 2024, 124, 1950−1991

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   4.1. Length Dependence                                  1963            polarized light. Chiral molecules that appear in organisms
   4.2. Effect of Chirality Type                           1963            (lipids, carbohydrates, nucleic acids, and proteins) are
   4.3. CISS Manifests for Individual Molecules            1963            homochiral, and even though the chemical behavior of
   4.4. Organization Effects on CISS                       1964            enantiomers is often very similar, their bioactivity is not.
      4.4.1. Orientation                                   1964            Although conventional wisdom considers changes in chemical
      4.4.2. Alignment                                     1964            behavior to arise from differences in shape (lock and key
   4.5. Conduction Mechanism and CISS                      1964            mechanism of binding and enzymatic function), the reasons for
   4.6. Spin−Orbit Coupling and Interface Effects          1964            homochirality and what might have guided Nature’s choice of
   4.7. Temperature Dependence                             1965            one enantiomer over the other in biomolecules have long
   4.8. Circular Dichroism as a Predictor of CISS          1965            intrigued chemists.1−3 Even more generally, one might ask,
   4.9. Relationship between CISS and Magnetic                             “Why is chirality, as such, preserved so persistently throughout
         Properties                                        1965            evolution?” or “What makes chiral symmetry so important to
5. Theoretical Understanding                               1966            life?” Answers to these questions could involve the relationship
   5.1. Early Models for CISS                              1966            between chirality and the electron spin, which manifests as the
      5.1.1. SOC and Orbital Models                        1966            chiral induced spin-selectivity effect (CISS). CISS refers to the
      5.1.2. Spinterface Models                            1967            connection between chiral symmetry and electron spin in
   5.2. Essential Features of a CISS Theory                1967            molecules and materials and it can manifest for electron




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   5.3. Chiral Molecule Interactions and Ferromag-                         transmission and for electron displacement currents.
         nets                                              1967               The idea that spin-polarized electrons scatter asymmetrically
   5.4. Open Issues                                        1968            from chiral molecules was explored soon after the discovery of
6. Prevalence of CISS and CISS Implications                1968            parity violation, i.e., the weak force breaks parity conservation,
   6.1. Spintronic Applications                            1968            by Lee and Yang.4 However, studies with chiral molecules in the
      6.1.1. Spintronic CISS Devices                       1968            gas phase gave scattering asymmetries of A < 10−4, where A = (I+
      6.1.2. Spin-Optoelectronics                          1969            − I−)/(I+ + I−) where I+ and I− are the intensities of the electron
      6.1.3. Superconducting Spintronics                   1970            beam with spin angular momentum parallel and antiparallel to
      6.1.4. Quantum Spintronics                           1970            the velocity. In 1999, we showed that the asymmetry in
      6.1.5. Future Directions                             1970            photoelectron scattering is >100-fold larger, ca. 0.1−0.2, when
   6.2. Enantioseparations/Enantiomeric Resolu-
                                                                           the electrons traverse through an ordered film of chiral
         tion                                              1971
                                                                           molecules.5 Subsequent studies, using the same approach,
      6.2.1. Enantiospecific Adsorption                    1972
                                                                           reproduced these findings for other chiral molecular adlayers.6−8
      6.2.2. Crystallization                               1972
                                                                           In 2006, Wei et al. first showed that the phenomenon manifests
      6.2.3. Future Directions                             1972
                                                                           for electron transport in electrochemical tunnel junctions,9 and
   6.3. Chemical Reactions                                 1973
                                                                           since that time a large number of tunnel junction measurements
      6.3.1. CISS Enhances Efficiency of O2 Reactions      1973
                                                                           and proximal probe studies have observed spin-dependent
      6.3.2. Organic Electrosynthesis                      1974
      6.3.3. Polymerization                                1975
                                                                           electron transport through chiral molecules and ultrathin chiral
      6.3.4. Future Directions                             1976
                                                                           films.10,11 In 2011, Göhler et al. used Mott polarimetry to
   6.4. Role of CISS in Biology                            1976            measure the photoelectron spin distributions through films of
      6.4.1. Biological Redox Processes                    1976            duplex DNA and found spin asymmetries as high as 60%.12 A
      6.4.2. Role of Electron Spin on Protein Stability    1976            perspective/mini-review of this early work in 2012 helped spark
      6.4.3. Biomolecular Interactions and Recogni-                        interest in this phenomenon, which is now called the CISS
              tion                                         1977            effect.13 Over the past decade, the number of publications using
      6.4.4. Allosteric Interactions                       1977            the term chiral-induced spin selectivity, and their corresponding
      6.4.5. Origin of Life                                1977            citations has grown considerably year over year (see Figure 1).
      6.4.6. Future Directions                             1977               This review aims to provide a more comprehensive
7. Critical Assessment of the Field                        1978            description of the field and current understanding of CISS-
8. Concluding Remarks and Future Outlook                   1978            related phenomena than that of reviews prior and comprises
Author Information                                         1978            eight parts. In the next section we overview the different
   Corresponding Authors                                   1978            methodologies that have been used to measure the CISS effect,
   Notes                                                   1978
   Biographies                                             1978
Acknowledgments                                            1979
References                                                 1979


1. INTRODUCTION
Since the time of Louis Pasteur, chiral symmetry and chiral
molecules have intrigued chemists. Chiral molecules exist as
stereoisomers, termed enantiomers, that are nonsuperimposable              Figure 1. Number of publications, and the citations of those
mirror-image structures of each other, like right and left hands.          publications, using the phrase “chiral induced spin selectivity” or
While the chemical formula and atomic connectivity of                      “chirality induced spin selectivity” from 2012 to 2022. The bars show
enantiomers are identical, their three-dimensional structure is            the number of publications each year, and the solid curve shows the
not and gives rise to distinctive interactions with circularly             cumulative growth in citations. Data are from Clarivate Web of Science.

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Figure 2. Representative schematic diagram (a) for the determination of CISS using Mott polarimetry measurements. First, photoelectrons in a
substrate are excited (i) and then transmit through the chiral spin filter (ii), resulting in a net spin polarization. The photoelectrons are scattered on an
Au foil target according to their spin (iii) and quantified at two independent detectors (iv). The schematic is reproduced with permission from ref 39.
Copyright 2022 American Chemical Society. Panel b shows the photoelectron spin polarization from a bare Au(111) substrate excited with clockwise
(green), linear (blue), and counterclockwise (red) polarized light. Panels c−e show the spin polarization for photoelectrons from an Au(111) surface
that is coated with double-stranded DNA for clockwise, linear, and counterclockwise excitation, respectively. The data are adapted from ref 12 with
permission. Copyright 2011 Science.

and then we follow with a section that summarizes the classes of                  when comparing findings between different measurement
molecules and materials shown to exhibit CISS. In Section 4, we                   techniques.
identify general trends and inferences that can be drawn from                        In addition to direct measurements, indirect probes for the
particular experiments described in Sections 2 and 3, and in                      CISS effect rely on the spin-selectivity of product formation in
Section 5 we provide a brief assessment on the current status of                  electrochemical reactions,18 or of charge polarization-induced
theory, and its advances, since the review published in 2022.14 In                spin polarization, and the complementary phenomenon of spin
Section 6, we describe some implications and applications of                      polarization-induced charge polarization, of chiral molecules
CISS for physics, chemistry, and biology. Lastly, we conclude                     and materials.19,20 In the latter case CISS has been shown to give
with a critical assessment of the field (Section 7) and then offer                rise to enantiospecific interactions, be they intermolecular or
some forward-looking sentiments (Section 8)                                       with ferromagnetic substrates,21,22 as well as spin-dependent
                                                                                  charge delocalization.19 It is important to note that CISS is often
                                                                                  a transient process, 23,24 particularly as it pertains to
2. METHODS FOR MEASURING CISS                                                     enantiospecific interactions or measurements affected by
Direct experimental determinations of the CISS effect fall largely                decoherence, vide inf ra; therefore, measurement time scales
into two main measurement modalities: the observation of spin-                    are important for revealing spin selectivity.25,26 Below we
dependent electron transport through chiral systems and the                       summarize different measurement techniques that have been
measurement of charge polarization-induced spin polarization                      used to probe the CISS effect in chiral molecules and chiral
of chiral systems. Transport/transmission measurements have                       materials.
been performed, both above the vacuum level (Section 2.1) and                     2.1. Photoelectron Spectroscopy
below the vacuum level (Section 2.2). While studies have
                                                                                  Spin-resolved photoemission of electrons through chiral
attempted to calibrate the magnitude of the CISS-response                         molecular films or ultrathin chiral materials is often considered
across different measurement techniques,15 this process remains                   the “gold standard” for quantifying the CISS effect because
challenging because of differences in how the measurements are                    measurement of the electron spin population is not convoluted
performed and how the CISS-response is quantified. In CISS                        with charge displacement currents. These studies have provided
studies the “spin polarization” has often been defined as the                     insights into the importance of molecular helicity and length, as
difference of measurables, for some process that selects for spin,                well as substrate spin−orbit coupling12,15,27−29 on the spin-
divided by their sum. For example, the CISS literature often                      dependent electron transmission. In cognate approaches,
defines polarizations as normalized anisotropies in electron                      researchers have begun to explore CISS effects indirectly, e.g.,
currents or charge transfer rate constants, and these quantities                  through shifts in the substrate work function30,31 and through
can be convoluted with the spin density of states. However, this                  spin-dependent electron-induced chemical reactions.32
treatment contrasts with classical definitions in which the spin                     2.1.1. Mott Polarimetry. Mott polarimetry has historically
polarization is formally given as the difference in populations for               been used for analyzing the magnetic characteristics of thin
spin up and spin down electrons.16,17 Thus, care must be taken                    films33−35 and characterizing spin-polarized electron sources,36
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Figure 3. Panel a shows the experimental geometry used for a measurement of the current−voltage curves. Panel b shows current−voltage curves for
peptide 1N with the linker on the N-terminus of the peptide. The blue curve corresponds to a South magnetized tip in which the electron transport is
aligned parallel with its spin and the red curve corresponds to a North magnetized tip in which the electron transport is aligned antiparallel to its spin.
Panel c shows current voltage curves for peptide 1C; in this case the South magnetized tip shows a lower current and the North magnetized tip shows
the higher current. Panel d plots the percent spin polarization, as calculated from the data in panels b and c for peptide 1N (green, 44%) and peptide 1C
(orange, −32%). The figure is adapted from ref 43 with permission. Copyright 2022 John Wiley and Sons.

among other applications.37,38 In this method electrons incident                   moment is affected by the substrate magnetization. As a result,




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on a crystalline solid with large spin−orbit coupling (e.g., Au)                   magnetization determines how much the adsorbates accept, or
scatter at different angles based on their spin orientation, and                   donate, charge density with the substrate and change the work
their angle dependent detection provides quantitative informa-                     function. Note that a spin-polarized detection scheme, such as
tion about the spin population of the electrons. See ref 38 for a                  Mott polarimetry, can also be used in tandem with UPS; work by
more detailed explanation and a historical perspective. For CISS                   Viswanatha et al. showed that the spin and momentum, both
studies, the typical process proceeds as follows: (i) electrons                    transverse and longitudinal, of the photoelectrons can be
from a substrate, or a chiral material,39 are photoexcited, (ii) the               resolved for 3-methylcyclohexanone adsorbates on Cu(643)
photoelectrons transit through (from) a chiral layer where spin-                   surfaces.27
filtering manifests, (iii) the photoelectrons are directed to a Mott
polarimeter and spatially resolved according to their spin. The                    2.2. Electron Transport
number of photoelectrons observed at the two detectors (gray                       Since the first report in 2006,9 many studies have explored spin-
spheres, iv) are used to determine the asymmetry or spin                           polarized electron currents through tunnel junctions of various
polarization, P (see Figure 2) through                                             types. Notably, studies also show that electron transport through
                                                                                   chiral semiconductors and chiral metals is spin-filtered. Thus,
         I+ I
   P=                                                                              CISS does not originate from a particular subclass of
         I+ + I                                                       (1)          conventional conductance mechanisms; however, it remains
                                                                                   unclear if the mechanism underlying the spin selectivity is
where I+ and I− correspond to the intensity of photoelectrons                      different for metallic conduction than it is for tunneling. To date,
measured at the two different detectors.                                           no correlation between reported spin polarizations and
   By way of example, consider an Au substrate. Excitation of an                   corresponding conductivities among different classes of
Au(111) surface with clockwise and counterclockwise circularly                     materials has been reported.42
polarized light produces spin-polarized photoelectrons with                           2.2.1. Conductive Probe Atomic Force Microscopy.
equal, but opposite, polarizations, whereas excitation with                        Magnetic conductive probe-atomic force microscopy (mc-
linearly polarized light does not give rise to a net spin
                                                                                   AFM) studies, in which a ferromagnetic electrode acts as a
polarization (see Figure 2b).12 Conversely, when the substrate
                                                                                   spin analyzer, are now available for a large range of organic and
is coated with double-stranded DNA, the polarizations
                                                                                   bio-organic molecules, hybrid organic−inorganic materials, and
measured for clockwise (Figure 2c), linear (Figure 2d), and
counterclockwise polarized light excitation (Figure 2e) was                        inorganic materials (see Section 3). mc-AFM measurements
negative, owing to the CISS effect. Similar studies have been                      display distinctive characteristics (vide infra) and are being
carried out showing the spin selectivity of other oligonucleo-                     widely used. It is important to note, however, that the geometry
tides,40 oligopeptides,15,40 metal oxides,39,41 and helicenes.28                   in which the experiment is performed can determine the sign of
For a recent review of CISS studies using Mott polarimetry, see                    the polarization; see ref 43 for a recent discussion on this topic.
ref 29.                                                                            Figure 3 exemplifies these features for the case in which the AFM
   2.1.2. Ultraviolet Photoelectron Spectroscopy. The                              tip is magnetized, either North or South, relative to the
determination of CISS using ultraviolet photoelectron spectros-                    molecule. The current voltage curve for the peptide 1N (Figure
copy (UPS) was first demonstrated by Weiss and co-workers for                      3b) shows that the current is higher when the tip is magnetized
α-helical peptides immobilized on Co/Pt ferromagnetic                              to select for electrons with their spins oriented parallel to their
substrates.30 Here, they measured changes in the photoelectron                     velocity (blue) as compared to the case in which the electron
energies as a function of North and South magnetization of a                       spins are oriented antiparallel (red) to their velocity. That is, the
Co/Pt substrate. A change in work function of ∼100 meV was                         magnitude of the current is higher when the electron spin
observed and attributed to the spin-dependent exchange                             direction and the electron velocity are aligned parallel. It is
interactions occurring between the chiral molecules and the                        common to define a percent polarization as
magnetized ferromagnetic substrate. Related studies on
ferromagnetic substrates by Kelvin probe force microscopy                                   jparallel    jantiparallel
have similar work function shifts.19 Because of the spin-selective                    P=                                 ·100%
                                                                                            jparallel + jantiparallel                                                  (2)
electron delocalization of chiral molecules, the surface dipole
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and this is plotted in Figure 3d for the peptide 1N (green). The               been performed by Bürgler and co-workers, who used spin-
same measurement on peptide 1C (linker attached to the C-                      polarized STM to examine the enantioselective adsorption of
terminus of the peptide rather than to the N-terminus) displays                chiral molecules on magnetic surfaces,47,48 and by Ortuño et al.,
an opposite behavior. That is, the current is higher for the case              who have developed a chiral oligo(phenylene)ethynylene based
where the spin is aligned antiparallel to the electron velocity (see           molecular tunnel junction and used theoretical calculations to
Figure 3c). An analogous dependence on the peptide’s                           predict spin polarizations of 20% to 40%.49 Collectively, these
attachment to the surface was reported from photoemission                      experiments demonstrate that CISS manifests at the single
studies.8,44                                                                   molecule level.
   The experimental mc-AFM studies have caused intensive                          2.2.3. Magnetoresistance and Spin Valve Studies. The
discussion because they display behavior that differs from those               mc-AFM method described in Section 2.2.1 can be viewed as a
commonly expected for magnetoresistance devices used in                        spin valve, in which the magnetic probe tip, or the substrate, acts
spintronics.45 Those devices are based on two ferromagnetic                    as the ferromagnetic contact. A vertical magnetic spin valve
electrodes comprising a “hard” magnet (high coercivity) and a                  device comprises a chiral film that is contacted on one side to a
“soft” magnet, with an insulating metal oxide layer, typically tens            normal metal electrode and on the other side to a magnetic
of nanometers thick, between them. In common magneto-                          electrode, whose magnetization direction can be changed by an
resistance devices, the current behaves as if it flows through a               applied external magnetic field. In this device, a magneto-
diode, namely one spin current is dominant under positive                      resistance is obtained from measurements of the current−




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voltage bias and the other under negative bias. This is not the                voltage response through the top and bottom contacts as a
case for CISS-based devices where the same spin-current is                     function of an applied magnetic field and probe how the chiral
dominant, independent of the voltage sign. In addition, CISS-                  film affects the magnetoresistance. This configuration was first
based devices often display spin polarizations that are higher                 used to measure spin-selective charge transfer through a self-
than what is expected for the magnetic layer acting as the                     assembled monolayer of polyalanine with a magnetized Ni
analyzer polarizer, which implies that the chiral molecular                    layer,50 and has since been used to evaluate the magnitude of the
junction must be nonlinear. In fact, the current in CISS-based                 CISS effect with other chiral systems.51 Unlike standard
junctions often depend nonlinearly on the voltage, see Section                 spintronic devices, in this configuration only one magnetic
3.1.1 and the discussion below.                                                layer is needed for a CISS-based device because the chiral axis
   The current−voltage data in the mc-AFM measurements can                     direction of the insulating layer determines the spin direction
be understood by considering a model in which the applied                      that is analyzed. In a four-probe setup it is possible to measure
voltage polarizes the chiral system and this charge polarization is
                                                                               the magnetoresistance without the contribution of the contact
accompanied by spin polarization (see ref 46). The model
                                                                               resistances. In this configuration, larger area devices are used and
considers a chiral molecular film located between two leads, one
                                                                               smaller magnetoresistance values are found; see ref 52 for further
of them a ferromagnet, and assumes that charge polarization of
                                                                               explanation and Figure 9 for a representative example. Note that
the chiral molecules by the applied voltage causes spin
                                                                               more elaborate spin-valve structures have also been used for
polarization. The positive pole of the chiral molecules is
                                                                               studying CISS.53,54
associated with one spin and the negative pole is associated with
the opposite spin in an enantiospecific manner, i.e., depends on                  2.2.4. Electrochemical Tunnel Junctions. The determi-
the handedness. Hence, electrons that have to penetrate into the               nation of CISS in a tunnel junction configuration was first shown
chiral system from the ferromagnetic electrode confront a spin-                using electrochemical methods on porphyrin terminated chiral
dependent barrier whose magnitude is proportional to the                       molecular scaffolds, L-Cys-(pro4(2S4S))4-Porph and D-Cys-
charge at the pole times the spin-exchange interaction. By                     (pro4(2R4R))4-Porph, immobilized on gold electrodes.9 Here,
assuming that the charge at the pole is about 10% of an electron               excitation of the porphyrin with circularly polarized light (left vs
charge and that the magnitude of the spin-exchange interaction                 right) created a spin-polarized population of porphyrin excited
is on the order of 1 eV, one finds the difference in barrier height            states and the subsequent photocurrent was measured.
for the two spins to be ∼100 meV. Indeed, experiments indicate                 Interestingly, a spin polarization (ca. 0.5%) in the photocurrent
that the difference in injection barrier for the two spins is of this          was observed with excitation polarization and was found to
order of magnitude, e.g., see ref 10. Such a barrier explains the              depend on the handedness of the molecular scaffold. The results
very high spin selectivity at room temperature. Other works have               were rationalized as spin-dependent processes affecting the
proposed “spinterface” models to explain these experimental                    electronic coupling. Similar results have been shown for chiral
signatures in a more quantitative manner (see Section 5.1).                    oligopeptide SAMs with tethered CdSe quantum dots on
   2.2.2. Scanning Tunneling Microscopy Methods. Diez-                         ferromagnetic electrodes placed in contact with a ferri-/
Perez and co-workers11 used scanning tunneling microscopy                      ferrocyanide redox couple; however, here the polarizations
(STM) break-junction measurements to show that CISS                            were determined by changing an applied magnetic field on the
manifests in single molecule junctions, i.e., the spin-filtering               electrode.55 Upon excitation, polarizations as high as 30% were
does not depend on having a chiral film, but can manifest at the               reported at the redox potentials of the ferri-/ferrocyanide and
single molecule level. In this work, they trapped individual                   the findings were corroborated by steady-state fluorescence
peptide molecules between a magnetized STM Ni tip and an Au                    measurements that monitored the asymmetry in quenching
electrode and measured the current. They found that the                        associated with electron transport to the electrode. Electro-
molecular conductance depends on the magnetization state of                    chemical methods have also been used to measure spin
the STM tip and on the enantiomeric form of the peptide. Note                  polarization in the dark; Kettner et al. observed changes in the
that these measurements did not display a perfect antisymmetry,                oxidation and reduction currents for ferri-/ferrocyanide
and it was necessary to invoke a spin-to-charge voltage (or                    solutions, using magnetized electrodes coated with oligopeptide
“spinterface” effect, see Section 5.1) to fully explain the data.              SAMs.15 The larger current response was found when the spins
More recently, CISS studies at the single molecule level have                  were aligned antiparallel to their momentum, in agreement with
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Figure 4. Panels a and b show a representative schematic diagram of a Hall device passivated with chiral oligopeptides. Panel c shows that upon charge
polarization of the oligopeptides, a transient Hall voltage is generated. Panel d shows the dependence of the Hall voltage on the magnitude and sign of
the gate voltage and the handedness of the oligopeptides. The figure is adapted from ref 20 with permission.

the conclusions drawn from photoemission measurements for                       through spin accumulation on a semiconductor. Recently, Xiong
the same oligopeptide assemblies.                                               and co-workers generated spin-polarized current by injecting
   Researchers have quantified changes in the charge transfer                   electrons from an Au electrode, which was coated with an α-




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rate, k0, of redox species attached to chiral monolayers. For                   helical polyalanine film, into a transport channel and detected
instance, ferrocene-oligopeptide composites immobilized on                      the spin accumulation at a GaAs electrode (Au/L-polyaniline/
gold showed an asymmetry in the charge transfer rate for                        Si:GaAs junctions).66 They observed universal temperature and
reduction and oxidation that depends on the handedness of the                   bias current dependences for the spin-polarized carriers. These
oligopeptide, e.g., for L-oligopeptides the k0 for reduction was                results provide further evidence that CISS-based spin polar-
faster than the k0 for oxidation and for D-oligopeptides the k0 for             ization can be detected without the use of a ferromagnet.
reduction was slower than the k0 for oxidation.56 This behavior                 2.3. Charge Polarization and Spin Polarization Methods
was attributed to an induced magnetization associated with the
oligopeptide assembly, similar to that shown in other works,57                  The methods in Section 2.2 rely on steady-state or periodic
and the CISS-mediated transport properties of the oligopep-                     charge currents; however, this need not hold for observing spin
tides. Experiments have also been performed on magnetized                       polarization in chiral molecules. Recent studies show that it is
ferromagnetic electrodes, so as to exclude spontaneous magnet-                  enough to charge polarize chiral materials transiently to generate
ization effects.58 In these studies cytochrome c was immobilized                a spin polarization, and that the complementary response in
on Cys-Ala-Glu tripeptide monolayers and electron transfer                      which a magnetization induces a charge polarization can
from the cytochrome c’s heme unit to the electrode was                          manifest.
measured. For tripeptide SAMs in which each of the substituents                    2.3.1. Spin-Dependent Polarization in Hall Voltage.
was levorotatory (LLL), a North applied magnetic field led to a                 Surface magnetizations, induced by the CISS response of a chiral
faster rate constant than a South magnetic field, whereas                       film, have been investigated using the Hall and anomalous Hall
tripeptide SAMs comprising all dextrorotatory substituents                      effects.20,67 Hall effect devices68 are widely used for continuous
(DDD) resulted in the opposite dependence, i.e., a South                        monitoring of spin-induced magnetization,69 and they com-
magnetic field led to a faster rate constant than North magnetic                monly have one of two configurations: a standard Hall bar
field. For SAMs with a heterochiral structure, e.g., LDL, the                   configuration and a van der Pauw square configuration.70 It is
electron transfer rates for North and South applied magnetic                    important to note that in shallow two-dimensional electron gas
fields were the same.                                                           (2DEG) devices the surface spins interact strongly with the
   The spin-specific change in charge transport through chiral                  2DEG through Ruderman−Kittel−Kasuya−Yosida (RKKY)
molecules in electrochemical tunnel junctions, be that through                  interactions.71 When spin-polarized electrons are injected into
monitoring changes in current or charge transfer rate, likely arise             III−V heterostructures (such as AlGaN/GaN or AlGaAs/GaAs)
from the same phenomenon: spin-dependent changes in                             that contain a 2DEG layer, the semiconductor becomes
resistance for charge transport. This supposition is supported                  magnetized, even at room temperature, with a magnetization
by recent impedance measurements made on DNA coated                             direction that depends on the direction of the polarization of the
ferromagnetic electrodes, in which an equivalent circuit model                  injected spins.72 For dry measurements, a shallow GaAs 2DEG is
analysis is used to extract the charge transfer resistance as a                 mostly utilized,67 while for liquid solutions GaN-based 2DEG
function of applied magnetic field.59−61 For the DNA                            are most used.72 The latter can also be used to monitor the spin
assemblies, deviations in charge transfer resistance with                       dependence of electrochemical processes.
magnetization orientation are observed, owing to the CISS                          In 2017, Kumar et al. used a Hall bar device to show that an
effect; however, in achiral systems the charge transfer resistance              applied voltage acting on a chiral oligopeptide film generates a
is unaffected by the magnetic field orientation.                                magnetization at the interface between the monolayer film and
    2.2.5. Hanle Rotation. The Hanle effect can probe the spin                  the Hall bar surface, even though no net current flows.20 Figure
polarization of carriers in a semiconductor by measuring their                  4a,b shows a schematic diagram of their experimental measure-
spin precession and dephasing as they propagate through a                       ment design. They constructed a Hall bar circuit, which was
transverse magnetic field.62,63 In addition to determining spin                 buried under a few nm thick film of GaN and then coated with a
lifetimes, Hanle effect measurements also report on pure spin                   self-assembled monolayer film. The application of a voltage
transport and on spin accumulation, which gradually reduces to                  between the bottom working electrode and the counter-
zero with increasing magnetic field strength.64,65 In traditional               electrode (G) creates a displacement current that charge
electrical Hanle measurements a ferromagnet is used to generate                 polarizes the chiral molecular film and generates a transient
a spin-polarized current in a transport channel that is probed                  Hall voltage signal (Figure 4c), which then decays. Upon release
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of the applied voltage, the film discharges and generates an                      Figure 5a,b shows topographical images of a patterned surface
opposite Hall voltage because of the opposite direction of                        on which L- and D-polyalanine monolayers are adsorbed, and the
current flow. Figure 4d shows that the signal increases with the                  corresponding magnetic force microscopy images in Figure 5c,d
magnitude of the applied voltage, which increases the charging                    show opposite magnetization directions. These findings
current, and that it is enantiospecific, i.e., a film of L-oligopeptide           establish that as chiral molecules and ferromagnetic layers
has a response opposite in sign to that of a film of D-oligopeptide.              come into contact, the spin-polarized current exchange between
Note that no magnetic materials and no external magnetic fields                   the chiral layer and the ferromagnet is very efficient in polarizing
are present in this experiment; the chiral charge polarization of                 the spins of the ferromagnet (Figure 5).50 In this case, about 1013
the molecules gives rise to a spin polarization at the bottom of                  electrons per cm2 are sufficient to induce magnetization reversal.
the film that manifests as a magnetization that acts on the charge                The direction of the magnetization depends on the handedness
carriers moving in the source drain channel.                                      of the adsorbed chiral molecules, i.e., it is enantiospecific. In
   The Hall circuit design can be incorporated into a working                     contrast, the current density required for the spin-transfer
electrode, which can be used to probe spin-selective charge                       torque in modern magnetoresistive random access memory is
transfer and charge displacement processes. The electro-                          106A cm2, or about 1025 electrons cm2/s, a trillion times higher.
chemical cell used in the above experiment was constructed to                     Note that the inverse effect, enantiospecific interaction of chiral
not display any Faradaic current, so that the oligopeptide-coated                 molecules with a magnetized substrate, can be used to separate
electrode surface would closely approximate an ideally polar-                     chiral molecules21 (see Section 6.2).




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izable electrode. If instead, one constructs an electrochemical                      2.3.3. Spin Exchange Microscopy. The enantiospecific
cell with a redox couple, then Faradaic current can flow and the                  interaction between chiral molecules and ferromagnetic surfaces
working electrode, with its embedded Hall device, allows one to                   enables one to perform locally resolved magnetic imaging by
monitor the spin dependence of redox reactions in addition to                     adsorbing chiral molecules on an AFM tip.78 This technique is
the charge currents that are traditionally measured.72 By using a                 based on short-range spin-exchange interactions that can be
working electrode that possesses an embedded Hall probe, one                      scaled down to atomic resolution and only require a conven-
can perform “3D spin electrochemistry”,73 i.e., measure the                       tional AFM tip functionalized with a chiral molecule. A direct
current, voltage, and spin simultaneously for redox reactions.74                  measurement of the force and tip displacement for the
   Most of the Hall signal induced by chiral molecule adsorption                  interaction between a ferromagnetic substrate and chiral
on metals and semiconductors seems to arise from the                              molecules provides energy for the interaction, and the difference
anomalous Hall effect.75 This was verified by experimentally                      in energy for the two magnetization directions (North versus
verifying the relation between the longitudinal and Hall                          South) of the ferromagnet allows one to determine the
resistance as a function of temperature.76                                        difference in exchange energies. The mean pulling energy
   2.3.2. Emergent Magnetic Properties and Magnetic                               showed a difference of 150 meV for sample magnetizations of
Force Microscopy. The spin polarization, which is generated                       North and South along the sample normal.
by the charge redistribution in chiral molecules, can be stabilized                  To illustrate the phenomenon, consider the interaction
in a ferromagnetic film. Figure 5 shows magnetic force                            between two helical molecules. When two chiral molecules of
microscopy images of lithographed surfaces in which chiral                        the same handedness interact, the charge polarization is
molecules, by virtue of their charge-polarization induced spin-                   accompanied by a spin polarization acting in the same direction,
polarization, imprint a magnetization onto a ferromagnet.57                       e.g., pointing outward along the helix axis (see Figure 6), and the
                                                                                  exchange interaction between the molecules’ excess spin
                                                                                  densities in the overlap region is characterized by two spin
                                                                                  polarizations aligned antiparallel. In contrast, the spin polar-
                                                                                  izations of two interacting molecules of opposite chirality would
                                                                                  be aligned parallel. The difference in these spin arrangements
                                                                                  generates a change in exchange energies.20 Note that the spin
                                                                                  polarization manifests even when the two molecules are each
                                                                                  closed shell; while they remain singlet states globally, their
                                                                                  electron clouds can locally display spin imbalances.
                                                                                     2.3.4. Kelvin Probe Force Microscopy. Probing the
                                                                                  surface potential that is induced by spin transfer can be achieved
                                                                                  using Kelvin probe force microscopy (KPFM). The basic Kelvin
                                                                                  probe measurement consists of a metallic probe electrode that is
                                                                                  placed near the sample surface to form a capacitor.79 Then, the
                                                                                  distance between the probe electrode and the sample surface is
                                                                                  changed periodically to generate a frequency dependent
                                                                                  capacitance. Thus, an AC voltage is created across the gap,
Figure 5. Topography and magnetic force microscopy phase images are               and it is proportional to the voltage difference between the probe
shown for a molecular-induced magnetization orientation. The top row              electrode and the sample. Rather than record the AC voltage
shows AFM topography images of SAMs of L-polylalanine (a) and D-                  directly, it is common to apply a DC voltage, referred to as the
polyalanine (b) adsorbed on Co thin ferromagnetic layers with a 5 nm
                                                                                  contact potential difference (CPD), to null the response. To
Au overlayer, and the bottom row shows their corresponding magnetic
AFM magnetic phase images (L-polylalanine (c) and D-polylalanine                  measure the CISS-induced spin wave function changes, the CPD
(d)). Adsorption of oligopeptides induce a magnetization, and the                 can be measured when altering the adsorbate’s enantiomeric
direction of the magnetization is controlled by the enantiomeric form of          form and the surface magnetization (see Figure 7). Kelvin probe
the molecules. The figure is adapted from ref 57 with permission                  measurements on ferromagnetic thin film electrodes coated with
(http://creativecommons.org/licenses/by/4.0/).                                    self-assembled monolayers of chiral molecules reveal that the
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                                                                                  2.4. Other Techniques
                                                                                  While studies of the CISS effect in chiral materials are most
                                                                                  prevalent using the techniques discussed above, a number of
                                                                                  other strategies have been demonstrated and are being
                                                                                  developed. Here, the manifestation of a CISS-response is akin
                                                                                  to that described previously, in that it arises from a spin-
                                                                                  dependent response in the material that depends on the
                                                                                  chirality.
                                                                                     2.4.1. Fluorescence. Fluorescence spectroscopy can
                                                                                  provide detailed information about relaxation and/or charge
                                                                                  and energy transfer processes that take place following light
                                                                                  absorption. Thus, if energy transduction is affected by spin
                                                                                  selectivity in a chiral system, then the photoluminescence of a
                                                                                  chromophore can report on the spin-dependence for the
                                                                                  transduction. For instance, researchers showed that the
                                                                                  photoluminescence of nanoparticles tethered to magnetized




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                                                                                  ferromagnetic substrates through chiral oligopeptides changes
                                                                                  with the orientation of an external magnetic field.55 Here, hole
                                                                                  transfer, and hence photoluminescence quenching, from the
                                                                                  nanoparticle to the substrate depended sensitively on the match,
                                                                                  or mismatch, between the spin selectivity of the oligopeptide
Figure 6. The image shows the effect of spin-dependent charge                     and the magnetization orientation of the substrate. Similar
reorganization interactions between two chiral molecules. From left to            measurements have been made in which spin-dependent
right: The two chiral reactant molecules are represented by helices and           electron transfer80 and energy transfer81 processes are
are noninteracting at a very large distance. As the chiral molecules
approach each other dispersion forces generate induced dipoles on each
                                                                                  responsible for controlling the chromophore’s photolumines-
molecule, which in turn are accompanied by a spin polarization. The               cence intensity with substrate magnetization.
two chiral molecules react to give a product with an energy that depends             In addition to steady-state fluorescence, time-resolved
on whether the spin polarizations on the molecules are aligned                    measurements can provide information about the importance
antiparallel or parallel.                                                         of spin on charge transfer kinetics. Such behavior was
                                                                                  demonstrated by studies of donor-bridge-acceptor nanoparticle
                                                                                  systems, in which the acceptor was made chiral.82 Here,
                                                                                  excitation of the donor nanoparticle with clockwise and
electron penetration from the metal electrode into the chiral                     counterclockwise circularly polarized light, thus yielding spin-
molecules depends on the ferromagnet’s magnetization                              polarized excitation of the donor, resulted in large differences in
direction and the molecules’ chirality. Figure 7b−d shows the                     charge transfer rates to the acceptor because of the CISS effect.
changes in the measured CPD with North (red) and South                            Note, however, that the efficacy of these measurements relied on
(blue) magnetizations for D-oligopeptide SAMs, achiral SAMs,                      several factors: (i) the system required a principal excitation axis
and L-oligopeptide SAMs, respectively.19 Electrostatic potential                  to define the electron spin orientation relative to that of the
differences as large as 100 mV are observed and arise from the                    transport trajectory, and (ii) the time scale for electron transfer
                                                                                  had to be shorter than the decoherence of the spin.
applied oscillating electric field, which drives spin-dependent
                                                                                     2.4.2. Resonance Spectroscopies. To date, only a handful
charge penetration from the ferromagnetic substrate to the                        of spectroscopy methods have been applied to the study of
chiral molecules. The large potential changes (>kT at room                        CISS; however, they are likely to prove very important in future
temperature) imply that this phenomenon is important for spin                     studies, because they can provide incisive information about
transport in chiral spintronic devices and for magneto-                           CISS when the chiral system is weakly coupled to its
electrochemistry of chiral molecules.                                             surroundings.




Figure 7. Panel a shows a schematic diagram for the Kelvin probe measurement. Panels b−d show changes in the measured contact potential difference
with North (red) and South (blue) magnetizations for D-oligopeptide SAMs, achiral SAMs, and L-oligopeptide SAMs, respectively on ferromagnetic
electrodes. The figure is adapted from ref 19 with permission. Copyright 2020 American Chemical Society.

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Figure 8. Panel a shows an experimental schematic for magneto-optic Kerr effect measurements on chiral perovskite thin films. Panel b shows
magneto-optic Kerr rotation measurements on S-hybrid organic−inorganic perovskites, under positive (top) and negative (bottom) out-of-plane
external magnetic fields. The red line is an adjacent average smoothing of the data. Panel c shows the change in photoinduced Kerr response as a
function of the external magnetic field strength. The red line is a linear fit to the data. The figure is adapted from ref 97 with permission. Copyright 2020
American Chemical Society.




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   2.4.2.1. Cross-Polarization NMR. Although “conventional                        spin-exchange microscopy (Section 2.3.3) measurements;
wisdom” holds that nuclear magnetic resonance (NMR)                               however, other methods for detection have also been employed.
spectroscopy is not sensitive to a molecule’s chirality unless it                 For instance, superconducting quantum interference device
is perturbed by a chiral bias of some sort, this assumption is                    (SQUID) magnetometry has been used to measure the effect of
overly simplistic. For example, Buckingham has shown that                         chiral molecules on the magnetic properties of materials; studies
NMR methods that sense odd parity magnetoelectric coupling                        show that superparamagnetic iron oxide nanoparticles adsorbed
terms should be able to directly probe chirality.83,84 In other                   on chiral self-assembled monolayers become ferromagnetic92
works, Ugalde and co-workers used CP-NMR to measure the                           and conventional superconductors may exhibit topological
solid-state NMR spectra of 15N nuclei for different enantiomers                   superconductivity when interfaced with chiral molecules.93
of amino acids, and found a systematic and significant increase in                   Another technique, which has been used to probe the CISS-
the signal levels for the D-isomer over that for the L-isomer, even               effect in chiral materials, is magnetic circular dichroism. Here, a
though the chemical shifts are identical.85,86 The CP-NMR                         magnetic field is oriented parallel or antiparallel to the direction
experiment transfers polarization from the majority nuclear                       of light and the differential adsorption of left and right circularly
spins (protons in this case) to the dilute minority spins (15N                    polarized light is measured.94 In a typical experiment, the
nuclei in this case) and the efficiency of this process is                        orientation of the external magnetic field determines the sign of
enantiospecific, giving rise to higher signal intensities for the D-              the optical activity. Conversely, when the CISS effect is stronger
isomer in their spectrometer. This finding implies that the                       than the effect imposed by the external magnetic field, a change
coupling, which leads to the polarization transfer, is                            in magnetic field orientation does not change the sign of the
enantiospecific and they propose a mechanism based on CISS                        optical activity. Such behavior has now been observed for chiral
to rationalize their findings. Experiments of this sort are                       mesostructured BiOBr and α-Fe2O3.95,96
important for studying fundamental features of CISS, because                         Spin transport from chiral materials to adjacent ferromagnetic
they do not have the complications associated with molecule−                      layers has been probed by magneto-optic Kerr effect (MOKE)
substrate couplings; rather, they probe the interaction between                   measurements in which a change in the magnetization of a
nuclei in the amino acid molecules, via the molecule’s CISS-                      magnetic material is monitored through changes in the
based electronic response.                                                        reflection of polarized light off its surface. Figure 8a shows a
   2.4.2.2. Time-Resolved EPR Studies. Electron paramagnetic                      schematic for MOKE measurements. Here, linearly polarized
resonance (EPR), or electron spin resonance (ESR), spectros-                      excitation of a chiral perovskite film creates a photoinduced spin
copy can provide a direct probe of spin polarization. Its use in                  current that magnetizes an adjacent ferromagnetic layer.97 The
CISS studies was first reported in 2020 by Ansermet and co-                       Kerr angle, reflecting the change in magnetization of the
workers to probe the spin polarization of paramagnetic radicals                   ferromagnetic layer, depends on the perovskite’s enantiomorph,
that are produced by electrochemical reduction at a chiral                        whereas achiral perovskites show no response. Figure 8b shows
electrode (i.e., Au coated with an oligopeptide).87 Since that                    the change in MOKE response upon photoexcitation of the
initial report, a number of other research groups have actively                   perovskites, and Figure 8c plots the change in Kerr angle with
pursued experimental and theoretical studies into identifying                     applied magnetic field. Experiments have shown that a change in
CISS signatures in EPR spectra and proposed photochemical                         Kerr response can occur upon photoexcitation or thermal
mechanisms to enhance them.26,88−90 Recently, Wasielewski                         activation of chiral layers because of CISS-mediated trans-
and co-workers have demonstrated that photoinduced electron                       port.97,98
transfer in a donor-chiral bridge-acceptor molecule gives rise to                    Note that other spectroscopic methods, such as optically
electron spin polarization in the biradical product, ca. 50%.91                   detected magnetic resonance via nitrogen vacancies in diamond,
   2.4.3. Magnetometry and Magneto-optical Methods.                               are also being used to measure magnetization effects for CISS
The accumulation of spin polarization at interfaces, or even self-                studies, e.g., reorientation of ferromagnetic layers upon
contained in chiral materials, has led to the use of magnetic-                    adsorption of chiral molecules.99
based detection schemes for monitoring the CISS effect. Indeed,                      2.4.4. Spin Seebeck Effect. In magnetic materials, spin
such behavior is responsible for the response in Hall devices                     currents can arise from temperature gradients by the conven-
(Section 2.3.1), magnetic force microscopy (Section 2.3.2), and                   tional spin Seebeck effect.100 Recently, Sun and co-workers used
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a temperature gradient to generate a spin selectivity effect in                   Point Chirality versus Helical Chirality. Helical chirality
chiral materials without any ferromagnetic layer, which they call             appears to give rise to stronger spin filtering than the point
the CPASS (chiral-phonon-activated spin Seebeck) effect.98 In                 chirality of individual stereocenters. Electrochemistry-based
this case the chiral phonon−electron coupling generates a spin                measurements show that folding DNA duplexes, comprising the
current because of the conservation of angular momentum, i.e.,                same nucleobase sequences, into right-handed or left-handed
the chiral phonons transfer angular momentum to the electron                  helices controls the sign of the spin-filtering, implying that the
spin angular momentum. CPASS provides a unique and incisive                   helical twist of the duplex DNA dominates over the point
probe for examining the importance of electron−phonon                         chirality of the sugars.102 This observation is consistent with
coupling for the CISS effect. CPASS could also be used to                     Mott polarimetry photoelectron studies using disordered films
distinguish between coherent and incoherent chiral pumping of                 of single-stranded DNA and oligopeptides that display poor
spin waves in thin magnetic films.101                                         spin-filtering.12
                                                                                  Dipole Orientation Effect. Both photoemission8,44 and mc-
3. MATERIALS AND MOLECULES EXHIBITING CISS                                    AFM measurements43 show that the sign of the spin-polarized
                                                                              current changes with the orientation of the molecule on the
Early experiments on CISS have examined spin-dependent                        electrode. That is, placing an oligopeptide on a metal substrate
electron transport and electron polarization with organic                     by its carbon end gives a different sign for the spin polarization
molecules, for which the structure and organization of their                  than binding it to the electrode by its nitrogen end.




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assemblies can be manipulated. More recent studies have shown                     Circular-Dichroism (CD) is a Predictor. Studies on
that CISS manifests for a wide array of molecular, supra-                     oligopeptides of the same length but different CD strengths
molecular, and materials types. CISS effects have been reported               (lowest energy) show that the spin filtering increases as the CD
for insulating, semiconducting, and metallic chiral solids; chiral            strength increases.43 This claim is corroborated by studies on
quantum dots, chiral 2D layered materials, and chiral polymers,               chiral quantum dots82 (see Section 3.2.2) and supramolecular
including biopolymers, and their assemblies. Here we overview                 structures128,129 (see Section 3.2.1).
these studies and identify key aspects about CISS, which they                     3.1.2. Helicenes. Although helicenes do not contain carbon
have revealed. Note that, a comparison across material types is               stereocenters, they possess axial chirality. CISS manifests in
discussed in Section 4.                                                       enantiospecific adsorption of helicenes to magnetized surfaces,
3.1. Molecules and Macromolecules                                             in spin-filtered electron transmission via photoelectron spec-
                                                                              troscopy, and in conduction experiments through monolayer
   3.1.1. DNA and Oligopeptides. DNA (see refs 7, 10, 12,                     films of helicenes.28,47,48,130−134 Although several classes of
31, 52, 59−61, 80, 102−111) and α-helical oligopeptides (see                  helicenes have been investigated, no reports have drawn a clear
refs 11, 15, 19−21, 30, 43, 44, 50, 52, 54−57, 67, 69, 72, 74, 77,            correlation between the structure of a helicene and its spin-
92, 99, 104, 112−126) have been widely used to explore the                    filtering power. Photoemission studies indicate some effect of
CISS effect and its connection with molecular properties.                     the substrate on the spin polarization; however, no simple
Having been investigated by spin-dependent photoemission,                     correlation was found between the spin−orbit coupling of the
transport, electrochemical, and spin-dependent polarization                   substrate and the size of the spin polarization in the CISS
experiments, they comprise testbed systems for comparisons                    effect.28 As a caveat, one must appreciate that different binding
between methods. These studies have provided a number of key                  groups are used for attaching molecules to the different
insights into CISS properties.                                                substrates and this can lead to different charge distributions at
   Polarization, P, as a Metric. For both families of molecules               the interface, hence work functions. Thus, the exact role of the
spin polarization exceeding 60% was found, when the polar-                    substrate remains an open issue and may require careful studies
                              j    j
ization, P, is defined as P = j+ + j with j+ and j− referring to the          to reach firm conclusions.
                               +                                                  3.1.3. Proteins. Experiments find that both redox proteins,
charge current measured when the magnetic North pole is                       as well as other proteins, display spin-polarized electron
pointing toward the adsorbed molecules or away from them,                     transport; including photosystem I, cytochromes, azurin, and
respectively; and these magnitudes compare well to those                      multiheme electron transfer conduits, among
observed by spin-polarized photoemission studies.15                           others.22,58,115,135−142 These observations are consistent with
    Length Dependence. Over the size ranges studied (<20 nm                   electron transfer via peptidic pathways in proteins. Beyond these
for DNA and shorter for oligopeptides), the P increases linearly              pioneering demonstrations, systematic studies have examined
with the length. It is found that the α-helices of oligopeptides are          the temperature dependence of spin filtering, the importance of
about a factor of 5× better spin filters than DNA, on a per                   homochirality in electron transfer, and the role of CISS in
nanometer basis.104 The length dependence of the spin                         allostery.
polarization results from the conduction of the favored spin                      Temperature Dependence. Temperature-dependent con-
decaying more slowly as a function of length than does the                    ductance measurements show that the spin-filtering decreases
unfavored spin.                                                               with decreasing temperature, even in cases where the overall
    Voltage Dependence. In the conduction studies performed                   conductance remains approximately constant. These studies
with the mc-AFM method, it was established that spin-                         imply that spin-dependent transport is activated, suggesting the
dependent conduction displays a power law dependence on                       importance of phonons for CISS to manifest.142 See Section 4.7
the voltage, with the power d being greater than one, and that a              for more discussion of temperature-dependence studies.
different voltage threshold for conduction exists for each of the                 Homochirality in Redox Chemistry. Because the linear
spin polarizations. The different thresholds imply that spin                  momentum of the electron and its spin are locked, back-
flipping during the conduction is not significant, i.e., a mixed              scattering in homochiral assemblies is suppressed, which makes
spin distribution would not generate different voltage thresh-                electron transfer more efficient. Measurements with the redox
olds.104,127                                                                  protein cytochrome c on oligopeptide films of differing
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enantiomeric forms show that the electron transfer rates in the                   Synergy of CISS and Spin Blockade. Spin filtering in chiral
heterochiral assemblies are suppressed, as compared to the                     molecules containing paramagnetic ions is enhanced over that in
electron transfer rates in homochiral assemblies.58                            molecules without paramagnetic ions, suggesting that CISS can
   CISS in Molecular Recognition. Spin dependent charge                        be combined with more traditional spin blockade ideas to
polarization in proteins affects allostery, enhancing or reducing              enhance spin filtering.122
reactivity at sites far from the binding position of the substrate. A             Chiral Supramolecular Constructs. Yamamoto and co-
recent study on the association of an antibody with its target                 workers showed that the assembly of achiral cobalt phthalocya-
protein antigen can be modulated by a ferromagnet, even when                   nines into helical supramolecular assemblies on ferromagnetic
the protein is bound to the ferromagnetic substrate at a site                  substrates can be controlled by the magnetization state of the
remote from the binding site.22,143 The charge reorganization is               surface. 162 This guided self-assembly is similar to the
modulated by the magnetization because the charge displace-                    enantioseparation of amino acids from racemic solutions by
ment currents in the protein are spin polarized.                               crystallization onto magnetized surfaces.
   3.1.4. Polymers. Spin-filtered electron transport and spin                     3.2.2. Chiral Inorganic Nanoparticles. The first report on
polarization manifests in chiral polymers and chiral polymer                   a semiconductor’s CISS response was in 2016, in which chirality
fibers.129,144−149 In a number of cases these films are grown by               was imprinted on CdSe NPs by surface ligands.163 Figure 9a,b
CISS-mediated processes (see Section 6.3.3). A major outcome
of these studies is the demonstration that spin-filtered electron




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transport can proceed over hundreds of nanometers to microns
in length. For example, Yan and co-workers showed that
polyaniline fibers spin-filter electron currents over length scales
of a few microns, along the chiral axis of the supercoiled fibers.144
The spin filtering is not restricted to transport along the polymer
chains, even current through thick (up to 120 nm) films of chiral
polymers display spin-filtered currents, see Figure 11. Similar to
the case of biopolymers, the spin-filtering is temperature
activated150 and a correlation exists between the spin polar-
ization and the strength of the CD signal.147
3.2. Inorganic and Hybrid Organic−Inorganic Materials
Reviews of chiral inorganic materials have recently become
available.151−154 Here we focus on CISS studies associated with
different classes of chiral inorganic and hybrid inorganic−
organic materials. Given the promise of CISS for interesting
applications in spintronics, optoelectronics, and catalysis, the
number of CISS studies with inorganic materials is expanding.
   3.2.1. Chiral Supramolecular Constructs. Inorganic
materials and organometallic supramolecular assemblies exhibit
CISS properties and can be combined with other functional
elements of supramolecular constructs for bespoke spin-
selective functions. For example, Therian and co-workers used                  Figure 9. Spin transport measurements on CdSe quantum dots
mc-AFM and spin-Hall measurements to show that chiral                          passivated with L-cysteine (a,c) and D-cysteine (b,d) ligands. Panels a
conjugated zinc-porphyrin molecular wires polarize spin                        and b show mc-AFM measurements in which the red curve corresponds
currents up to 32%.155 Incubating the as-assembled chiral                      to the electron spin antiparallel to its momentum and the blue curve
molecular wires in binucleating ligands of the opposite                        corresponds to the electron spin parallel to its momentum. The shaded
                                                                               regions represent 95% confidence intervals. Panels c and d show
handedness causes a flip in the circular dichroism response                    corresponding magnetoresistance (MR) measurements on spin-valve
and corresponding spin-filtering properties of the assembly. In                devices. The data are replotted from ref 163 with permission. Copyright
other work, Cardona-Serra and co-workers used cyclic                           2016 American Chemical Society.
voltammetry, electrochemical impedance spectroscopy, and
transport studies to show that incorporation of paramagnetic                   shows mc-AFM measurements for studies on 2.2 nm CdSe
Tb3+ lanthanides into helical peptides leads to higher spin                    nanoparticles passivated with cysteine molecules where an
polarizations compared to metallizing with diamagnetic Yb3+.122                ∼33% polarization at negative bias and ∼15% polarization under
The spin-filtering properties of the paramagnetic helical                      positive bias was observed, in spite of the nanoparticles showing
metallopeptides were later used to construct a memristor.156                   only a modest chiroptical response (∼0.5 mDeg).163 Moreover,
In other studies, Sang et al. showed that helical nanofibers                   a spin-valve device was constructed using the chiral nano-
composed of achiral benzene-1,3,5-tricarboxamide molecules                     particles and the data showed an asymmetric magneto-response
with an aminopyridine group that could coordinate to Ag(I)                     in a manner consistent with the favorable spin alignment found
display spin polarizations of ∼45%,157 and Mtangi et al. showed                for mc-AFM
that chiral Zn-porphyrin stacks display polarizations of                          In other works, assemblies comprising CdSe-polyalanine
∼35%.158 Even much simpler organometallic complexes,                           multilayers, using a layer-by-layer approach,164,165 display a large
which possess stereocenters as opposed to chiral secondary                     excitation polarization dependent change in fluorescence
structures, exhibit CISS properties (see Wang et al.159 and Miwa               lifetime (∼3.5× longer for CW excitation than CCW) that
et al.)160,161                                                                 was attributed to symmetry breaking-induced changes in
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nanoparticle coupling and spin delocalization.164 The enhanced                 valley pseudospins,176−178 to realize spin-mediated photo-
delocalization between nanoparticles separated by long helical                 galvanic and photovoltaic devices,179 and to create circularly
polyalanine was superior to that found in other experiments                    polarized light detectors169,174,180,181 (see Section 6).
using short-chain achiral molecules,166 and thus, could prove                     The perovskite film studies reveal a number of important
useful for design strategies in parallel computing applications.               aspects for CISS-based materials as well.
   Chiral quantum dots have also found a number of applications                   Length Dependence and Mechanism. The studies on films
examining fundamental CISS issues and exploring device                         show that spin-filtered electron currents can propagate over
concepts.                                                                      hundreds of nanometers,168 rather than the few nanometer
   Electron Transfer Rates and CD Correlation. Electron                        limits observed for molecules. Measurements as a function of
donor-bridge-acceptor dyads, comprising an achiral CdTe NP                     film thickness support a mechanism in which the chiral organic
donor and a chiral CdSe NP acceptor, were used to demonstrate                  molecule layers spin-filter the electron currents and compensate
how spin-filtering in chiral assemblies affects electron transfer              for loss of spin purity as the propagation proceeds.
rates.82 The electron transfer rate asymmetry, (ket,CW − ket,CCW)/                The Role of Chiral Phonons. Kim et al. showed that a spin-
(ket,CW + ket,CCW), was found to correlate with the strength of the            polarized current, which depended on the perovskite’s handed-
circular dichroism spectrum for the acceptor NPs first exciton                 ness and an externally applied magnetic field, manifests when a
transition, and the maximum asymmetry was 88%. These studies                   chiral perovskite is subjected to a thermal gradient.98 The spin
showed that the rates can be described by a Marcus electron                    polarization was attributed to a chiral-phonon-activated spin




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transfer picture in which the electronic coupling is affected by               Seebeck (CPASS) effect.
CISS.                                                                             3.2.4. Transition Metal Dichalcogenides (TMDs). A
   Optospintronic Memory Architectures. Spin selective                         collection of works on chiral TMDs has recently been published
electron transfer between chiral NP constructs and a substrate                 and further expands the landscape of materials known to exhibit
have been used to write local magnetizations corresponding to                  CISS properties. Duan and co-workers showed that intercalating
logical memory.118 The spin selectivity of electron transfer with              chiral molecules into TaS2 and TiS2 TMD layers provide
chiral CdSe NPs has been exploited to demonstrate a 9-state                    structurally robust materials with large spin polarizations, ca.
volatile-like spin-memory device.167                                           60%.182 Interestingly, spin tunnel junction devices made from
   3.2.3. Hybrid Organic Inorganic Perovskites and Metal                       the materials show magnetoresistance exceeding 300%, over an
Halides. The initial work explicitly demonstrating CISS in R-/                 order of magnitude larger than that observed in previous CISS-
S-methylbenzylammonium (R-/S-MBA) lead iodide perovskite                       based systems. Other methods for preparing chiral TiS2 have
2-D layered thin films was shown by Vardeny and co-workers                     also been demonstrated.183 In related studies, Bian et al. report
and displayed spin polarizations as high as 92%.168 Similar                    spin-polarized electron currents as high as 75% through 5 μm
findings have since been reported in hybrid organic−inorganic                  thick films of MoS2184 and greater than 90% in >100 μm TiS2
perovskites and metal halides with other compositions as well                  crystals.185
(see Table 1). In related work, researchers have incorporated                     The spin polarizations generated in chiral molecules and
                                                                               materials may also prove fruitful when interfaced with TMDs to
Table 1. mc-AFM Determined Spin Polarizations of Different                     break valley state degeneracy. Research on single monolayer
Hybrid Organic−Inorganic Perovskites and Metal Halides                         MoS2 and WSe2 interfaced with chiral perovskites showed
                                                                               changes in the degree of valley polarization and the effect was
          Compositiona                Polarization (%)       Ref.
                                                                               attributed to the spin-selective charge injection from the chiral
    (R-/S-MBA)2PbI4                         92               168               perovskite, i.e., CISS.177 A similar enhancement in valley
    (R-/S-MBA)2PbI4/CsPbBr3                 80               171
                                                                               polarization was also observed when D-histidine was interfaced
    (R-/S-MBA)PbBr3                         90               172
                                                                               with a monolayer of MoS2.186 Here, the spin-dependent charge
    (R-/S-MBA)2SnI4                         94               173
                                                                               redistribution properties of the histidine, and strong hybrid-
    (R-/S-MBA)4Bi2Br10                      84               174
                                                                               ization between histidine and the MoS2, led to the degree of
    (R-/S-MBA)2CuBr4                        92               175
                                                                               polarization at the +K valley being 7.73% and the −K valley
    (R-/S-MBA)2CuCl4                        92               175
                                                                               being 1.6%. Note that spin-dependent charge redistributions in
    (R-/S-NEA)2CoCl4                        90               170
a
                                                                               chiral molecules can lead to spontaneous magnetization,20 and
 R-/S-MBA is R-/S-methylbenzylammonium; R-/S-NEA is R-/S-1-                    application of external magnetic fields to TMDs can cause a
(1-naphthyl)ethylamine.                                                        Zeeman energy splitting that increases valley contrast.187,188
                                                                                  3.2.5. Metal Oxides. A wide array of chiral magnetic oxides
achiral additives into the chiral matrix in order to improve the               are becoming available and offer promise for a range of
film crystallinity, yet retain their spin-filtering power.169,170 For          applications.189 Interest in chiral metal oxides for CISS-
instance, Lee et al. showed that the addition of urea to (R-/S-                applications stems from initial research showing that electrodes
MBA)2PbI4 perovskites causes structural changes to the                         coated with chiral molecules reduces the reaction overpotential
perovskite host, which can enhance the chiroptical response                    for the oxygen evolution reaction compared to analogous
and ensuing spin polarization measured by mc-AFM.169 The                       electrodes coated with achiral molecules (see Section 6.3.1).41
spin-filtered currents in these materials can persist over                     By adapting the electrodeposition methods developed by
thicknesses of hundreds of nanometers, and it is hypothesized                  Switzer and co-workers,190,191 chiral CuO coated electrodes
to arise from multiple tunneling processes through the chiral                  were studied by Mott polarimetry and shown to exhibit spin
organic molecules occupying the space between the layered                      polarizations of ∼10%.39 In related experiments, the spin
octahedral perovskite sheets.168                                               polarization through cobalt oxide surfaces was shown, using mc-
   The spin selectivity of perovskites in photoinduced transport               AFM and Hall device measurements.192,193 More recently,
has been leveraged for spin-polarized charge injection from                    Ghosh et al. showed that doping cobalt oxide thin films with 5%
perovskites into transition-metal dichalcogenides to manipulate                Mn afforded an ∼2-fold enhancement in the spin polarization
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Figure 10. Panel a shows a schematic which illustrates the atomic molecular deposition super cycle repeated a total number of “L” times until a desired
thickness is achieved. The deposition is composed of two subcycles; atomic layer deposition (blue) of alumina using trimethylaluminum and water
repeated “n” times followed by dosing of the film (red) with D- or L-alaninol repeated “m” times. Panel b shows j−V characteristics of a device with a film
fabricated using L-alaninol precursors for two different magnetic field directions; the inset illustrates the measurement circuit design. Panel c plots the
resulting spin polarization as a function of bias potential. This figure is adapted from ref 195 with permission. Copyright 2022 American Chemical




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Society.

(55−60%) compared to the undoped chiral thin film (25%),192                       metals, demonstrate that CISS-based, spin-polarized charge
whereas Bai et al. showed that helical stacking of NiOx                           currents persist over micrometer to centimeter distances. Inui et
nanoflakes leads to 50−80% spin polarizations.194                                 al. first illustrated this fact for chiral CrNb3S6 bulk crystals by
    Studies of transition-metal oxides manifest the interplay                     detecting the spin-polarized charge current by an inverse spin
between chiral symmetry and magnetic ions, or materials. By                       Hall signal (voltage drop).53 The Hall signal, and hence spin
comparing magnetic circular dichroism (MCD) spectra for                           polarization, was found to depend sensitively on the current
helically stacked nanoflakes, Bai et al. showed that chiral α-                    direction as well as the handedness of the chiral crystal. The spin
Fe2O3, which is antiferromagnetic, exhibits a chirality-depend-                   polarization in these crystals persisted over micron length scales,
ent/magnetic field-independent MCD response whereas the                           much longer than that of conventional achiral materials with
ferrimagnetic Fe3O4 and γ-Fe2O3 nanoflakes exhibit a chirality-                   lower spin−orbit interactions,196 and were hypothesized to arise
independent/magnetic field-dependent MCD response.95 They                         from antisymmetric spin−orbit interactions, i.e., the chiral
conclude that magnetic field effects in the ferrimagnetic metal                   materials did not exhibit normal spin-flipping processes. In
oxides are stronger than the magnetic field generated by CISS,                    follow-up experiments by the same group, the CrNb3S6 crystals
whereas the CISS effect dominates for antiferromagnetic                           were shown to manifest bulk magnetization when an electric
materials. Other measurements on metal oxides indicate that                       current was applied along the principal chiral axis of the
chiral symmetry can influence the magnetic ordering of a                          crystal.197 The presence of CISS in inorganic crystals is not
material. For instance, asymmetric adsorption of chiral                           limited to CrNb3S6 systems; recent studies have expanded the
molecules on a 10 nm superparamagnetic iron oxide nano-                           library of crystals to include chiral Te, NbSi2, and TaSi2;198−201
particle caused the material to become ferromagnetic.92 In                        and theoretical works on SnIP double helices are argued to give
analogous experiments, vibrating sample magnetometer meas-
                                                                                  rise to spin-dependent velocity asymmetries in electron
urements showed that achiral CuO films were diamagnetic,
                                                                                  transport as well.202
whereas chiral CuO films were mostly paramagnetic with a weak
                                                                                      Spin Transport up to Centimeters. Studies on chiral
ferromagnetic hysteresis.39 The emergent properties were
                                                                                  crystalline rods of NbSi2 and TaSi2 demonstrate that chirality-
hypothesized to arise from canted spins associated with a
chirality-induced asymmetric lattice; however, more experi-                       based spin polarization can persist for centimeters in length.203
ments are necessary to confirm such behavior.                                         Inverse CISS Manifests. Studies using CrNb3S6 in device
    Spin-Dependent Electrocatalysis. A combination of meas-                       structures demonstrated the existence of an inverse CISS effect,
urements for spin-filtered currents and for water electrolysis                    i.e., a pure spin current induces a charge current.53
demonstrate the usefulness of CISS for directing chemical                             3.2.6.2. Chiral Metal−Organic Frameworks and Crystals.
heterogeneous chemical reactions through spin control (see                        In a landmark paper by San Sebastian and co-workers, a
Section 6.3.1).                                                                   paramagnetic metal−organic framework, composed of Dy(III)-
    Nonmagnetic Oxide Spin Filters. Recent work by Al-                            tartrate, showed near-ideal spin-filtering capabilities (∼100%)
Bustami et al. shows the promise of chiral metal oxides as spin                   and spin polarization in the charge transport persisting over 1
filters in spintronic applications. By using atomic and molecular                 μm length scales.204 The remarkable performance was attributed
deposition techniques (see Figure 10), they created chiral                        to the large spin−orbit coupling of the Dy(III) lanthanides in
Al2O3/organic hybrid films with a near 100% spin polar-                           tandem with the helicity of the metal−organic framework along
ization.195 This represents the highest spin-polarized electron                   multiple crystallographic directions, leading to multichannel
current, obtained via CISS, for a device structure.                               spin-selective electron transmission. A similar behavior has also
    3.2.6. Bulk Crystals and Organometallic Constructs. In                        been observed in 300 nm thick Cu(II)phenyl alanine crystals,
the past five years, workers have shown that CISS phenomena                       with mc-AFM measured polarizations up to ∼68%.205 Notably,
are not restricted to ultrathin films and molecules but can also                  these crystals display a transition from antiferromagnetic to
manifest in bulk solids.                                                          ferromagnetic at 50 K that was explained by the emergence of a
    3.2.6.1. Inorganic Chiral Crystals. Recent experiments on                     low-lying thermally populated ferromagnetic state, which arises
bulk crystals, ranging from insulators to semiconductors and                      from interactions among Cu(II) species mediated by the chiral
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lattice. Newer work on Co(II)-phenylalanine crystals reports
polarizations of 35−45%.206
   Circular Dichroism (CD) as a Predictor. Comparisons
between Cu(II)phenylalanine and Cu(II)pentafluoro-phenyl-
alanine crystals show that the circular dichroism response of the
crystal is a good predictor for the sign of the spin polarization,
rather than the structural enantiomorph.205 This finding
corroborates such correlations reported in nanomaterials,
molecules, and supramolecular assemblies.
3.3. Summary
                                                                            Figure 11. The plot shows the dependence of the spin polarization on
The diversity of chiral molecules, molecular assemblies, and                the thickness for the polymer synthesized on a ferromagnetic electrode
materials support the notion that CISS arises from an underlying            with application of an oriented external magnetic field. The inset shows
relationship between electron spin and chiral matter that                   the average current versus voltage (j−V) curves recorded for 60 ± 3 nm
manifests because of the chiral symmetry. The knowledge                     thickness polymers with the magnet North pole pointing up (red) and
amassed from the numerous experiments is defining the criteria              down (blue). The figure is adapted from ref 150 with permission.
necessary for maximizing the CISS-response in a given system                Copyright 2022 American Association for the Advancement of Science.
and researchers are already using them to realize spin




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polarization magnitudes in excess of 99%.195,204 The knowledge
gained from experiments like those described in Sections 3 and 4            strongly with increasing film thickness. Figure 11 shows
is necessary for understanding CISS and developing a                        electropolymerized chiral films of poly(2-vinylpyridine) in
comprehensive theory for CISS-based phenomena.                              which the spin polarization increases monotonically up to a
                                                                            thickness of ∼120 nm, even though the chiral polymer strands in
4. GENERAL TRENDS AND STRUCTURE−PROPERTY                                    the film are disordered with respect to each other.
    RELATIONSHIPS                                                           4.2. Effect of Chirality Type
Although a quantitatively accurate mechanism for describing the             Molecules manifest chirality through stereoisomerism, which
CISS effect has yet to be identified, experimental work has begun           includes planar chirality, axial chirality and/or helical chirality,
to identify structure−property relationships for chiral molecules           and point chirality, which arises through dissymmetry in bond
and materials that must be accounted for by a comprehensive                 connectivity about an atomic center (typically carbon).
theory. In this section we overview the different trends observed           Although CISS manifests for all of the chiral types, responses
in experiments, comment on their pervasiveness, and identify                for axial or helical chirality appear to dominate over others in
important questions that must be addressed for continued                    organic systems. For instance, mc-AFM measurements on
progress in the field.                                                      single-stranded DNA yields no discernible spin polarization,
4.1. Length Dependence                                                      whereas polarizations as high as 57% were found for double-
                                                                            stranded DNA.10 Similarly, Stremer et al. introduced a Hg
For CISS, the most well-studied trend is the relationship
                                                                            chelating unit to single-stranded DNA, which creates a chiral
between the length through which an electron traverses and the
                                                                            secondary structure, and observed the emergence of a spin
resulting spin polarization of its charge current. Systematic
                                                                            polarization.31 The effect of helical structure on spin polarization
studies of DNA and oligopeptides, using a range of different
                                                                            was also observed for peptide-nucleic acids (PNAs). PNA with
techniques (photoemission spectroscopy, mc-AFM, electro-
                                                                            modified backbones, in which the monomer units become
chemistry, and Hall device measurements), show that spin-
                                                                            chiral, create helices with a shorter pitch length and result in
filtering of the charge currents increases monotonically with the
                                                                            higher spin polarizations than their unmodified counterparts.40
length of the molecules.10,12,15,74,104,207 Most studies in
                                                                            These studies also imply that point and structural chirality of a
molecular films and assemblies have been limited to a few tens
                                                                            material may be synergistic. Possible evidence of this synergy is
of nanometers or less, however. For example, Mishra et al.
                                                                            shown by measurements on B-DNA, for which the helix and the
examined the correlation between the length dependence of the
                                                                            stereocenters along the backbone are both right-handed. B-
optical activity and the spin-filtering performance of oligopep-
                                                                            DNA exhibits larger spin polarizations than do measurements
tides and DNA for film thicknesses <15 nm.104 Recently, Clever
                                                                            on Z-DNA, for which the helix is left-handed and the
et al. analyzed CISS data on DNA and oligopeptides and found
                                                                            stereocenters along the backbone are still right-handed.102
that the trend of increasing polarization with increasing length
                                                                            Unfortunately, the helicity of B-DNA and Z-DNA is different
was consistent among independent studies, even though the
                                                                            and so a clear distinction on the underlying mechanism cannot
absolute magnitude of the reported polarizations varied.43 The
                                                                            yet be made. Also the effect of helicity on spin polarization was
increase in spin-filtering performance per nucleobase in the case
                                                                            shown for a series of peptides that were systematically altered
of DNA and per amino acid in the case of peptides are different,
                                                                            through amino acid substitution at fixed oligopeptide length.43
however.
                                                                            Here, the spin polarization increased sequentially with the
    In addition to these studies on molecular systems, studies on
                                                                            increased helical content of the peptide. Because of the similar
chiral organic−inorganic perovskite films168 and studies through
                                                                            composition between peptides, this system is ideal for exploring
different thicknesses of chiral polymer films150 display an
                                                                            the relationship between helicity and differences in length
increase in spin polarization for thin films and then plateaus at
                                                                            dependence on spin polarization.
large film thickness. Although it seems likely that phonons and
structural imperfections in molecular assemblies would reduce               4.3. CISS Manifests for Individual Molecules
the spin polarization above a certain length, recent experiments            Although most studies of CISS have been performed on
on the spin filtering of electron currents through chiral polymer           organized assemblies or ensembles, a few experiments show that
films indicate that the spin polarization does not decrease                 CISS manifests for single molecules. Xie et al. used mc-AFM
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measurements of an assembly comprising ferromagnetic                          Co/Au substrates, where the coercivity and easy-axis of the
electrode/DNA duplex/Au nanoparticle molecular junctions                      magnetic cobalt layer is thickness dependent.19 The magnitude
to probe the spin-filtered current transmitted by the DNA                     of contact potential difference measurements, associated with
duplexes.10 While these studies do not unequivocally show that                spin-dependent changes in electron delocalization into/out of
the spin-filtering is a single molecule process, they do show that            the chiral molecules, correlated with the Co film’s easy-axis.
spin-filtering can occur through a few molecules, at most. In                    Note that the sensitivity of spin-polarized electron transport
other work, Diez-Perez and co-workers used STM-break                          on the orientation and alignment complicates comparisons of
junction experiments to study spin-filtered electron currents                 spin-filtering for different molecule types. For example, do the
through peptides and found that the sign of the spin polarization             differences in spin-filtered currents between oligopeptides and
changes with the chirality of the molecules.11,208 While these                DNA arise from intrinsic molecular differences or from
studies demonstrate that the spin-filtered currents manifest for              differences in their tilt-angles relative to the electron current
single molecules, the interpretation of the data require that one             direction? Experiments show that heterogeneity or structural
include some spin-filtering from the ferromagnet-molecule                     disorder can decrease the CISS response, or even result in a null
interface.                                                                    response, as shown in ref 23, and must be considered when
   In a recent tour-de-force study, Guo and co-workers used single            interpreting experiments. Indeed, some of the largest reported
molecule junctions and their CISS response to monitor chiral                  spin polarizations are for comparatively rigid well-defined
symmetry breaking in real time for a chemical reaction.209 Here,              constructs not susceptible to the same types of disorder found




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Ni/Al2O3/graphene/single molecule/graphene/Cr/Au molec-                       in organic molecule self-assemblies, e.g., metal−organic frame-
ular junctions were used to monitor the spin-filtered steady-state            works (>99%),204 bulk crystals (>70%),205 metal halides
electron currents. They measured the spin-dependent electron                  (>90%),170,175 and perovskites (>90%).168,172,173 Further
current through the molecular junction while it was exposed to                evidence corroborating this idea is shown for metal oxides in
reaction conditions for the addition of a 1,3-dicarbonyl to the               which films fabricated through electrodeposition techniques,
maleimide functionality. The spin-polarized electron current                  possessing ill-defined crystallinity, exhibit worse polarizations
reported on the chirality of the molecule as it underwent                     (ca. 10−25%)39,41,192 than that of metal oxides formed through
reaction. These studies demonstrate the single molecule nature                atomic and molecular layer codeposition techniques (>99%).195
of CISS and a new approach for probing chiral symmetry                        4.5. Conduction Mechanism and CISS
breaking during chemical reactions.                                           Spin-filtering of electron currents through chiral molecules and
4.4. Organization Effects on CISS                                             chiral materials manifests despite large apparent differences in
Control over the structural organization of chiral materials                  electron conduction mechanisms. For example, the electron
relative to the propagation direction of the electron is pivotal for          transport in photoemission experiments proceeds largely by free
maximizing the electron spin filtering. This principle is evident             particle motion (a few eV or less above the vacuum level)
in many studies and was even apparent in early work that showed               through chiral films, albeit with some scattering possible,
strong spin-filtering in organized molecular films but weak-to-no             whereas electron tunneling measurements on insulating films of
spin-filtering in disordered and/or impure films. In addition to              the same chiral molecules display similar polarizations for the
this general observation, the sense of the spin filtering has been            spin-filtered currents.15 Moreover, researchers report spin-
shown to change with the orientation of chiral helices at surfaces            filtered electron currents through insulating, metallic, and
and with the alignment of the helical axis to the electron                    semiconductor materials which possess widely disparate trans-
propagation direction. These effects are also evident for                     port mechanisms. This diversity suggests that different detailed
investigations into the enantiospecific interaction of chiral                 mechanisms may be required to describe the spin-filtered
molecules with ferromagnetic surfaces (see Section 6.2).                      electron currents in each case, but that they originate from
   4.4.1. Orientation. Carmeli et al. were the first to show that             attributes associated with the chiral symmetry.
the sense of the spin selectivity changes with the orientation of             4.6. Spin−Orbit Coupling and Interface Effects
chiral molecules on a surface. Using poly-D-alanine, they showed              Spin−orbit coupling (SOC) has been used to explain the
that the photoelectron intensity was higher (lower) for right                 emergence of spin selectivity in chiral materials5,13 and forms the
(left) circularly polarized excitation when it was attached to the            basis of early theoretical approaches to CISS;210−213 however,
surface through the C-terminus; however, the opposite was true                experiments give conflicting results. For instance, Rosenberg et
when attached via the N-terminus.8,44 Corresponding contact                   al. showed that the electron spin polarization decreases at higher
potential difference measurements showed that the dipole                      kinetic energies,103 in agreement with theoretical predictions.212
direction of polyalanine assemblies depend on the terminus                    Conversely, photoemission-based transmission experiments
containing the cysteine linker group, implying a relationship                 through ssDNA, with Hg2+ incorporation to form a chiral
between spin polarization and the molecular dipole direction. In              secondary structure, did not show a correlation between the
a different study a similar phenomenon was observed; mc-AFM                   amount of Hg2+ and the magnitude of asymmetry in spin-
measurements on peptides assembled through the N-terminus                     dependent scattering through the layer.31 While it is possible
and C-terminus gave opposite polarizations.43                                 that a correlation with Hg2+ loading was below the sensitivity of
   4.4.2. Alignment. The alignment of the electron spin in                    the measurement technique employed, it is also possible that
relation to the chiral axis of a molecule is another important                chelation of Hg2+ did not form an inherently chiral complex and
variable which should be optimized to maximize the CISS                       therefore the global secondary structure of DNA alone
response. Using STM measurements, Nguyen et al. reported                      determined the asymmetry in spin-dependent scattering.
weaker spin polarizations (∼60%) for chiral polyalanine clusters              Changing the SOC of the substrate does not appear to be a
than for self-assembled polyalanine layers (∼75%).113 This                    viable strategy for probing the role of SOC in photoemission, as
phenomenon was clearly demonstrated in Kelvin probe                           Mott polarimetry experiments on helicene coated Cu(332),
measurements of Ala-Aib oligopeptides assembled on tapered                    Ag(111), and Au(110) gave slightly different spin polarizations,
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but differences in binding to the different substrates may have              process and is only weakly temperature dependent, P1 is the
clouded any discernible trends with SOC.28 To further                        polarization of the ferromagnet and is proportional to (1 −
understand the role of SOC in CISS, more detailed experiments                αT3/2) in which α is a spin-wave parameter of the material that is
are required that systematically tailor the SOC without                      temperature-independent, and P2 is the spin selectivity of the
introducing other features known to contribute to the spin                   chiral layers and attributed to electron−phonon interactions. At
selectivity. Theoretical studies have shown how orbital-overlap              low temperatures P2 was found to dominate and the GS
and hydrogen bonding networks can alter SOC214 so studies                    increased with increasing temperature. Conversely, at high
should exclude structural dependent changes when assessing the               temperatures where P2 no longer changes with temperature, P1
role of SOC. Moreover, experiments on metallopeptides showed                 dominates and an inverse power law on GS with temperature was
that incorporation of Tb3+ resulted in higher spin polarizations             observed. The complex nature of the system in the above
than analogous measurements incorporating the heavier                        example illustrates how features other than CISS, such as the
lanthanide, Yb3+.122 The lack of correlation with SOC were                   polarization of the ferromagnetic “analyzer” and inherent spin-
attributed to differences in magnetic properties of the                      independent conductance of the material, can affect the
lanthanides, paramagnetic vs diamagnetic, superseding the effect             temperature dependence observed for a given system. More-
of SOC. Differentiating SOC effects from that of other features              over, these results suggest that experiments probing the
that can change the CISS-response is challenging.                            temperature dependence over a narrow regime may paint an
4.7. Temperature Dependence                                                  incomplete picture of temperature effects.




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A distinguishing feature of CISS, in contrast to other modalities            4.8. Circular Dichroism as a Predictor of CISS
for generating spin-filtered currents, is its robustness at ambient          Several research groups have used the circular dichroism
temperatures, and a broad understanding of the CISS temper-                  properties of chiral materials as a figure-of-merit for the CISS
ature dependence, or lack thereof, may prove important for                   response. This was initially demonstrated for donor-bridge-
understanding its mechanism. In several early magneto-                       acceptor nanoparticle dyads in which the acceptor nanoparticle’s
resistance measurements, the CISS-response for devices                       ligand shell was systematically varied to control the chiral
composed of both organic and inorganic chiral materials                      imprinting on the nanoparticle’s density-of-states.82 The
appeared to be invariant with temperature.121,130,163 The                    magnitude of the electron transport asymmetry, with clockwise
behavior was surprising because it contrasts with traditional                and counterclockwise excitation, was found to scale proportion-
giant magnetoresistance-type devices which show a general                    ally with the circular dichroism intensity of the nanoparticle’s
trend of increasing magnetoresistance with decreasing temper-                first excitonic transition. Similar behavior has been observed in
ature.215,216 In other works, chiral dipeptide-coated carbon                 experiments on polymers,129 oligopeptides,43 and naphthalene
nanotube networks exhibited a decrease in magnetoresistance                  derivatives207 where changes in the helicity of the system were
asymmetry with increasing temperature and a null response at                 reflected in the circular dichroism strength and the spin
temperatures >50 K.217,218 The magnetoresistance response for                polarization. Intuitively, a correlation between a material’s
these studies, however, was convoluted. At low temperatures                  chiroptical properties and the material’s propensity to act as a
both spin-dependent, e.g., CISS, and spin-independent                        spin filter seems sensible�the larger the dissymmetry factor, the
processes occur. At elevated temperatures the electrons begin                larger the expected spin polarization.
to conduct through thermionic emission, a non-spin-selective                    Structural and organizational features strongly influence the
process. In 2017, a similar series of temperature-dependent                  sign and magnitude of the CISS response, and they need to be
magnetoresistance measurements were made for assemblies                      considered. For instance, studies on the adsorption kinetics of L-
comprising bacteriorhodopsin, and the magnetoresistance was                  cysteine on magnetized ferromagnetic surfaces (North vs South)
found to increase with increasing temperature.137 the findings               show a range of asymmetries in the adsorption rate with the
on bacteriorhodopsin measurements were corroborated in later                 magnetization direction (see Figure 14).23,221 Whether the
works on azurin, oligopeptides, Pb-phthalocyanine complexes,                 asymmetry is positive, negative, or nil can depend strongly on
and DNA.52,142,161 While temperature-induced conformational                  the pH of the solution, despite the Cotton effects remaining
changes of materials are known to affect the CISS-response,67                mostly unchanged in situ. For this case, cysteine’s adsorption is
the cause for discrepancies among the magnetoresistance                      known to change its tilt angle and dipole direction with pH and
measurements is currently unknown. It is important to note                   this must be taken into account for interpreting the data
that some of the prevailing theories on CISS implicate vibronic              quantitatively. Such an assessment was recently used for
contributions to the spin selectivity and therefore suggest that an          explaining Hall measurements on some amino acids and so far
increase in temperature should increase the spin polar-                      appears to hold.43 Moreover, other studies show that using the
ization.52,142,219,220                                                       CD for the relevant transitions, i.e., those associated with the
   A recent report by Qian et al. on the spin-polarized                      interacting moiety, provides robust qualitative relationships
conductance through chiral molecular intercalation super-                    between the sign of the CD and the resulting polarization.222
lattices, chiral TMDs, may offer some explanation for why                    4.9. Relationship between CISS and Magnetic Properties
different behavior is observed.182 In their study the average
conductance, G(T), through chiral TMDs was attributed to both                Spin exchange interactions in chiral materials give rise to new
spin-independent, GSI(T), and spin-dependent, GSI(T), con-                   magnetic properties. For example, materials have been found in
tributions such that                                                         which the ferromagnetism increases with temperature for a given
                                                                             temperature range, and current-induced ferromagnetism has
   G(T ) = 2GSI (T ) ± 2GS(T )                                 (3)           been observed in chiral crystals that contain paramagnetic
                                                                             atoms.205 Another interesting finding is the conversion of
where GSI(T) was consistent with a thermally activated hopping               superparamagnetic nanoparticles to ferromagnetic ones at room
process, proportional to e1/T, and GS(T) was modeled to be                   temperature, by adsorbing them on a monolayer film of chiral
proportional to GTP1P2, where GT is the elastic direct tunnelling            molecules.92 These findings indicate that interesting new
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multiferroic properties may emerge when combining chirality                   be important for systems with unpaired electrons and/or
with ferroic materials.                                                       systems with large spin−orbit coupling (SOC). In addition, the
   A range of works show that transient charge redistribution in              effect is order(s) of magnitude larger in the experiment than
chiral molecules produces a spin polarization that acts as a                  what one calculates with simple single electron models. The
magnetization. Such a behavior forms the basis of the Hall                    temperature dependence is also surprising as Zeeman energy
response (Section 2.3.1),20,118 magneto-optic Kerr sig-                       splittings are typically small, one expects that spin-related
nals97,112,160 in chiral composites (Section 2.4.3), and                      properties will decrease with increasing temperature, whereas
imprinting of magnetization on ferromagnetic substrates                       CISS appears to be activated, at least in some cases. In addition,
(Section 2.3.2).50,92,223 The handedness of the chiral molecules              spin-dependent transport properties are observed commonly
and their orientation on the surface control the magnetization                with two contact electrical configurations, which appears to
direction.57,112 The magnetic properties of the individual                    violate Onsager’s reciprocity.14 Moreover, recent experiments
components that comprise larger architectures are also thought                show that charge polarization-induced spin polarization, which
to influence the CISS-response; itinerant electron spins in chiral            is a dynamical response, can be used to create metastable
inorganic crystals are hypothesized to give rise to the long-range            magnetic states.99 That is, the interaction of chiral molecules
transport of spin polarization.198,199 In other works, ferrimag-              with a magnetic substrate is enantiospecific and can align the
netism was found in chiral organic donor−acceptor crystals and                spins in the substrate, e.g., induce ferromagnetism in a
was attributed to the chirality-dependent spin polarization.224               paramagnet.




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The inherent magnetic properties of metal oxides, can also
supplant or suppress the spin polarization as was shown for                   5.1. Early Models for CISS
chiral ferrimagnetic Fe3O4 and γ-Fe2O3 nanoflakes,95 as well as               The initial theoretical approaches can be divided into two main
NiFe2O4 mesostructured films.225                                              classes. In the first, the Hamiltonian possesses chiral symmetry
   How does CISS influence the magnetic properties of a                       and the spin−orbit coupling is treated as a parameter. These
material? Because chiral materials create spin-polarized electron             calculations show spin-dependent transport; however, the
populations, either during transport or through displacement                  magnitude of the spin polarization is small even when the
currents arising from electron density changes, adjacent                      SOC is much larger than that known for hydrocarbons. The
materials and/or orbitals can accumulate spin density.                        second class of approaches assume that spin selectivity arises
Identifying what states, however, is a complicated task. Millo                primarily from the chiral molecule/substrate interface, or
and co-workers showed that the adsorption of helical molecules                “spinterface”.
on NbSe2−Au junctions resulted in new low-energy spin-                           5.1.1. SOC and Orbital Models. Simplified models that
polarized bound states, similar to Yu-Shiba-Rusinov states, that              account for spin−orbit coupling (SOC) in describing the
change in density, but not bias potential, with applied magnetic
                                                                              electron motion have recently been reviewed, see refs 14 and
fields.119 Proximity effects associated with these magnetic
                                                                              235. Although scattering models produce spin filtering, the spin
defect-like states in relation to superconducting properties is
                                                                              polarization magnitudes are too low.236 By re-examining the
explored in several works;226−229 and a similar mechanism,
                                                                              origins of SOC from the Dirac equation, workers have identified
chirality-induced formation of new states, has been used to
describe current-induced magnetization in chiral Cu(II)phenyl                 a geometric SOC, which scales with the first power of the
alanine crystals.205 How prevalent these states are among chiral              electron mass rather than the second power, and gives rise to
materials and their assemblies has not yet been determined.                   significantly higher magnitudes for nanoscale helices than what
   The role of exchange interactions on the magnetic response,                one might expect by considering the traditional atomic SOC.237
and subsequent spin polarization, have also been explored.230                 This geometric SOC has been used to model chirality-induced
While CISS-associated proximity effects are expected to be a                  spin transport in chiral hybrid organic−inorganic perovskites.238
short-range phenomenon,228 exchange interactions can occur                       Scattering models can help build an intuition for CISS.
across larger length scales and are thought to form the                       Consider a thought experiment in which an electron is incident
foundation for enantioselective processes between chiral                      on a gold surface at some angle, a Mott scattering experiment.
molecules and magnetized ferromagnetic surfaces (see Section                  After striking the Au surface, the electron’s scattering angle
6.2).21 The robust nature of exchange interactions in CISS was                depends on the direction of its spin angular momentum relative
recently shown by Ziv et al. in which the surface spin polarization           to the surface. The event is analogous to the classical picture of a
of a chiral molecule coated AFM tip was used as a substitute for              spinning disc, Frisbee, scattering from a wall for which the
magnetic tips in magnetic force microscopy.78 In what way the                 scattering angle depends on whether the Frisbee is rotating
resulting spin polarization is affected, however, is hard to define.          clockwise or anticlockwise. Hence, if a detector for electrons is
In other works, studies point to exchange interactions affecting              placed at a given angle relative to the surface normal, this
the tilt angle between chiral molecule SAMs and an applied                    detector will detect preferentially electrons with one spin. The
magnetization axis,99,114 the organization of cellulose crystals,231          ability to detect spin is a result of breaking the space inversion
and the stability of proteins.232                                             symmetry, by having the gold surface located either to the right
                                                                              or to the left of the electron source. The other necessary
5. THEORETICAL UNDERSTANDING                                                  condition is the SOC, which couples the orbital angular
Since its discovery, many researchers have considered CISS to                 momentum of the electron (relative to the gold surface normal)
be a “theoretical mystery”. While CISS has a firm basis from                  and its spin. Together, these two properties behave as an
symmetry considerations,233,234 the magnitude of the effect and               effective magnetic field.239 A chiral system breaks space
some of its novel manifestations challenge conventional                       inversion symmetry and if it has SOC, then it behaves like a
wisdom.51 For example, CISS manifests in closed shell organic                 Mott scatterer. Hence, counter to some claims,240 it is possible
and biologically relevant molecules with low atomic number                    to measure the spin selectivity of a chiral system by a two point
nuclei, whereas spin properties are commonly believed to only                 contact method.14
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   5.1.2. Spinterface Models. Motivated by the need for a                      without the need for high order perturbations. In chiral systems,
large SOC and a realization that the early CISS experiments                    an electron transiting through a helical electrostatic potential,
were performed with supramolecular assemblies of chiral                        can exchange angular momentum with the molecule through
molecules on metal electrodes, researchers have considered                     interaction with low frequency vibrations that carry angular
mechanisms in which the substrate electrode enhances the                       momentum, i.e., chiral vibrations. This process can manifest in
SOC.241−244 First proposed by Gersten et al.,245 this approach                 an accumulation of Berry phase for the passing electron. This
has recently been developed by Liu et al,.242 Dubi,243 and                     breakdown of the BO approximation has been accounted for in
others.246−249 In these models the substrate’s SOC, which can                  recent models to calculate the SOC.253−258 Clearly the SOC
be much higher than that of a typical organic molecule, converts               terms under the non-BO conditions are much larger, and
orbital angular momentum, arising from the electron motion                     interestingly they contain the spin-exchange interaction that has
through a chiral molecule, into spin angular momentum. In this                 a very large value, on the order of 1 eV, for molecules. In general,
picture the molecule is an orbital filter and the transmission                 it seems that any quantitatively accurate CISS model should
through the interface generates the spin selection. Given that                 include non-Born−Oppenheimer effects.
photoemission experiments for helicene monolayers on                              Recent models, which treat the CISS effect beyond the “single
Cu(332), Ag(111), and Au(110) substrates do not display                        electron model”, provide new insights and correspond better
large differences in spin polarizations, despite their quite                   with experimental observations.52,259 These models imply that
different SOCs,28 this mechanism is unlikely to apply to                       the role of electron-vibrational coupling (or polar-




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electron transmission above the barrier. For conduction                        ons)52,220,260−268 and electron−electron interactions219 will be
measurements, however, this phenomenon may be a contributor                    essential for explaining CISS. At present it seems that the
to the overall spin filtering. A recent report by Xiong and co-                solution for the large effective SOC should arise from electron−
workers examined chiral molecule spin valves with two different                phonon and electron−electron interactions. Recent measure-
metals (Au and Al) and two different molecules. They report                    ments on the temperature dependence of spin filtering have
significant differences in the polarization of the conductance                 motivated a number of different theory groups to explore the
between these systems, both between the two metals with the                    role of electron−phonon coupling in CISS. As the features
same molecule and between the two molecules for the same                       needed to describe CISS adequately coalesce, the development
metal.250 Together, these findings indicate that both the                      of ab initio calculation methods is becoming possible, albeit
molecule and the spinterface are important to consider.                        daunting. Even qualitative models should include the chiral
   Although the spin is not necessarily a “good” quantum                       molecule’s magnetoelectric polarizability and its dependence on
number for an electron moving through a chiral potential,                      electron-vibration interactions, as well as electron−electron
especially if SOC exists, it is still valid to ask whether the chiral          interactions when delocalized electrons, like in aromatic or
molecule selects for spin or orbital angular momentum. Clear                   highly degenerate systems, are involved.
evidence for spin selection is provided by EPR studies,72 in                   5.3. Chiral Molecule Interactions and Ferromagnets
particular recent published work that identifies spin polar-
ization.91 In addition to the photoemission studies described                  Numerous experimental observations show that chiral mole-
above, other experiments point to spin being selected. The                     cules interact enantiospecifically with magnetized surfaces and
anomalous Hall effect studies indicate that spins are injected                 that chiral molecules can imprint magnetization onto
from the adsorbed molecule into the Hall device. The same is                   ferromagnets. These experiments have spurred a new effort in
true in the case of the Hanle effect studies (see Section 2.2.5).              theoretical developments aimed at identifying the nature of
The interaction of chiral molecules with ferromagnetic materials               electronic spin exchange between chiral molecules and metal
and the ability to induce magnetization by adsorbing chiral                    surfaces.230,269−274 Cuniberti and co-workers used spin-
molecules, all support the “spin selection” concept.                           polarized DFT to examine the spin-dependent DOS at
   Despite their limitations, simplified models can provide useful             molecule-ferromagnet interfaces and showed that the interfacial
insights into CISS and molecular properties.251,252 By way of                  states are locally spin-polarized but remain singlet states globally,
example, recent work by Mujica uses an “electron on a helix”                   i.e., broken spin symmetry manifests at chiral molecule-
model to explore the relationship between circular dichroism                   ferromagnet substrate interfaces.230 These findings are corrobo-
and CISS. They find a clear correlation between the spin-                      rated by other model-based studies of chiral molecule
polarized electronic response and the circular dichroism of the                adsorption at interfaces.270−272
helix, suggesting a deep connection of CISS-based phenomena                       The imprinting of magnetization on a substrate by chiral
and chiro-optical phenomena through the electronic properties                  molecules and charge polarization-induced spin polarization
of chiral matter.252                                                           implies that intermolecular forces between chiral molecules
                                                                               ought to be spin dependent. Although recent experimental
5.2. Essential Features of a CISS Theory                                       studies support this inference (see Sections 2.3.3, 2.4.2, and
A comprehensive theory for CISS may require that we abandon                    6.4.3), more experimental work is needed to elucidate this
the Born−Oppenheimer (BO) approximation, which is                              phenomenon more fully. Theoretical interest in this aspect of
commonly used in models and calculations. When an electron                     CISS is growing. In early work, Kumar et al. performed DFT
propagates through a molecule in a path that is not linear, it must            calculations of the interaction energy between methyl groups of
exchange angular momentum with the molecular system. If the                    interacting chiral molecules and found a chirality and spin-
system is metallic and a band structure exists, the momentum                   dependent interaction energy of about 5 kJ/mol at a 2.5 Å
exchange can occur with the delocalized electrons in the system.               carbon−carbon distance.20 Geyer et al. have extended these
For molecules, however, the electrons are typically localized so               ideas by constructing a model for London dispersion forces that
that changing their momentum requires high energy or mixing                    includes intermolecular spin−orbit coupling, i.e., charge
through excited states. In contrast, a transiting electron can                 fluctuations on one molecule induce spin fluctuations in a
exchange momentum with low frequency vibrations (phonons)                      nearby molecule.273 Recently, however, Hedegård has critically
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evaluated spin-dependent charge reorganization for molecules                 CISS-based analogues to existing spintronic device structures
interacting through dipole−dipole fluctuations, and finds that               and phenomena.
the spin-polarization they manifest is quite small.274 This latter              6.1.1. Spintronic CISS Devices. Two common spintronic
work implies that coupling to a bath and/or vibrational degrees              technologies, which are used today, are magnetic tunnel
of freedom are needed to explain the magnitude of the effect                 junctions286,287 and spin transfer torque memory.288,289 In
reported experimentally. This area represents an important                   both, the spin polarization is performed by inorganic spin filters.
frontier in CISS research and could have important implications              In the magnetic tunnel junction/spin−valve memory, a fixed
for enantioselective chemical and biochemical processes.                     magnetized layer is separated from a second free magnetic layer
5.4. Open Issues                                                             by a thin isolating layer. The free layer can be magnetized either
                                                                             parallel or antiparallel to the magnetization of the fixed layer and
Many questions, beyond quantitative agreement with experi-                   the measured resistance depends on the relative orientations of
ment and the origin of the large effective SOC, can be posed.                the magnetization in the two ferromagnetic layers. Despite their
   1. Does CISS select electron spin or, more generally, an                  attractiveness, these devices suffer from a number of draw-
      electron’s total angular momentum?                                     backs,290−292 including the minimum ferromagnetic domain size
                                                                             and impedance mismatch between metals and high-resistivity
   2. What is the relation between optical activity and CISS?
                                                                             materials.293 Also, spin transfer torque memory requires high
      Are there other “predictors” for CISS, e.g., a molecule’s
                                                                             write currents, ca. 106 A/cm2.294 Although new methods, such as
      frequency-dependent magnetoelectric polarizability?




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                                                                             spin−orbit torque magnetic random-access memory,295 are
   3. Does the CISS mechanism change as the mode of                          being explored, they make production more complicated. In
      conductance (insulators, metals, etc.) in a material                   contrast, CISS-based devices do not require a ferromagnetic
      changes? If so, how and why?                                           layer to produce spin current, because the chiral layer produces a
   4. What is the temperature dependence of CISS in different                very high spin polarization.46,168,276,296 The CISS effect has been
      systems?                                                               used to generate 10−30 nm ferromagnetic domains (see Figure
   5. What can theory teach us about the role of entanglement                12).297 These devices operate many orders of magnitude more
      and coherence in CISS?

6. PREVALENCE OF CISS AND CISS IMPLICATIONS
The electron spin often plays a supporting role to the electron
charge in science and technology. Even the first electronic
computers used the electron charge for memory storage. While
the electron spin plays an essential role in chemistry, it is often
more of a “book-keeping device” (application of Pauli exclusion)
because magnetic interaction strengths are commonly much
smaller than Coulomb energies. The discovery of CISS, which is
robust at ambient temperatures and manifests for a wide range of
systems and environments, opens new possibilities for
ascertaining the benefits of spin control in technologies and
requires that we reexamine our assumptions about the electron                Figure 12. SEM image of a single magnetic nanoparticle spintronic
spin’s importance in chemistry and biology. In this section, we              device. Because of its CISS properties, the active memory device, which
discuss applications and implications of CISS for spintronics,               is about 30 nm in size, presents a memristor-like nonlinear logic
chemical separations, chemical reactions, and molecular biology.             operation at low voltages under ambient conditions. Inset: The active
                                                                             memory is the 30 nm magnetic quantum dot covered with chiral
6.1. Spintronic Applications                                                 molecules that is located between the two gold electrodees.
The CISS effect offers a new approach for fabricating simple and             Unpublished work.
efficient spintronic devices.275,276 The ultimate goal of
“spintronics”, short for “spin electronics,” is to develop new               efficiently than standard spin torque transfer memories and are
technologies based on the transport of electron spin, with the               straightforward to fabricate, replacing one of the magnetic layers
hope that they will have advantages over conventional charge-                by a chiral film.
based electronics, such as lower power dissipation.277 To date,                 6.1.1.1. Spin Valves. The simplest CISS-based spintronic
spintronics developments have impacted computer memory                       devices are spin valves that are controlled by an external
technology, both in terms of hard-disk capacity and of                       magnetic field.298 While they are simple to fabricate and present
nonvolatile magnetic random-access memory.278,279 Although                   a two-level resistance behavior, they are hard to control locally
spintronic devices are attractive for data storage, data transfer,           because switching between states is achieved by the field.50,121 In
and memory,279,280 they rely on transferring spin-polarized                  organic spin valve devices, spin polarizations of more than 95%
electrons from one ferromagnetic layer to another ferromagnetic              have been measured for conductive and paramagnetic crystalline
layer through a nonmagnetic barrier.281−285 This fact is limiting            3-D metal−organic frameworks (MOFs), based on Dy(III) and
                                                                                                       204
because the minimum size of ferromagnetic domains is                         L-tartrate chiral ligands.    A major breakthrough was the finding
constrained by the ferromagnetic-superparamagnetic transition                that thin metal oxide films (oxides of aluminum,195 cobalt,192,299
occurring in materials, typically on length scales of tens of                and copper41) can be made chiral and they display CISS-based
nanometers or larger. Chiral materials, or chiral molecules, in              spin filtering. These materials can be integrated with conven-
which spin polarizations can approach 100%,195,204 offer the                 tional microelectronic technologies and become part of CISS
opportunity to make ultrasmall (molecule scale) and efficient                based spintronics devices. Using 5 nm thick chiral oxides CISS-
spin filters and spin injectors.46,276 Below, we discuss some                based spin-valve devices were developed that are compatible
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with integrated circuits technology and display high spin                     emitting diode (CP-LED) efficiency is control over the spin
polarization (close to 100%).195                                              degree of freedom of charge carriers, i.e., radiative recombina-
   Because charge polarization in a chiral potential is                       tion of spin-polarized carriers can produce circularly polarized
accompanied by spin polarization, films of chiral molecules are               light.304,305 CISS presents an exciting opportunity for circularly
intrinsically multiferroic and promise the ability to locally                 polarized electroluminescence because the typical components
control their magnetization with a locally applied voltage. In fact,          and complex architectures used for generating the spin-polarized
self-assembled peptide films have been shown to generate a local              carriers can be replaced with intrinsically chiral materials that act
magnetization at room-temperature that depends on the sign of                 as spin filters. The concept of using CISS to generate the spin-
the applied voltage,20,77 creating localized magnetic fields on the           polarized carriers for CP-LEDs was first demonstrated by Beard
order of 100 Oe at room temperature solely by applying a small                and co-workers, in which they leveraged the spin-filtering
gate voltage (∼0.1 V). The magnetization is believed to arise                 properties of 2D-perovskites to promote spin-polarized
from spin-polarized charge density that is created at the                     recombination in achiral perovskite nanocrystals with 2.6%
substrate-chiral molecule boundary because of charge polar-                   circularly polarized electroluminescence (PCP‑EL) at room
ization of the organic molecules. Such devices offer the promise              temperature.171 Note that, researchers have used a similar
of electric field control over the magnetization locally. Although            device geometry, i.e., a perovskite spin transport layer, with
the switching rate of existing devices is low, in the megahertz               ZnS(CdSe) quantum dots as the recombination sites to create
range, their time response could be improved by miniaturization               CP-LEDs.310 In subsequent studies, Ye et al. showed that core−




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and device designs that make the charge displacement currents                 shell perovskite nanoparticles, in which the core was achiral and
coherent.                                                                     the shell was chiral, achieves circularly polarized electro-
   6.1.1.2. Spin Memristors. A primary challenge for reducing                 luminescence as well, with PCP‑EL = 0.6% at room temper-
the dimensions of existing memristor spintronic devices is the                ature.311 For this system the chiral shell acts as the spin-filter to
requirement for high spin currents; however, the CISS effect                  inject spin-polarized carriers into the achiral core. Note that,
provides a more efficient approach. A single nanoparticle, along              CISS-mediated CP-LEDs are not limited to perovskite
with Au contacts and chiral molecules, is sufficient to function as           materials. In other work, Mustaqeem et al. used chiral metal−
a memory device. A single ferromagnetic nanoplatelet has been                 organic frameworks as the spin injection layer and an impressive
used as a fixed hard magnet, and the Au contacts act as soft                  PCP‑EL was observed at ZnS(CdSe) core−shell recombination
magnets that result from chiral imprinting by the chiral                      sites; ca. 12.4% at room temperature.312 The large PCP‑EL was
molecules.297 The active memory device can be miniaturized                    attributed to enhanced spin-coherence lifetime of the charge
from a micrometer scale to 30 nm in size.                                     carriers.
   A larger memristor device can be achieved using chiral                        6.1.2.3. Circularly Polarized Light Detectors. A “simple”
metallo-bioorganic crystals, in which the memristor behavior                  detection scheme for circularly polarized light (CPL), which
depends on trapping of both charges and spins. In this case the               does not depend on complex optical components, is of special
crystal displays standard memristor behavior while the chiral                 interest for quantum optics313,314 and communications
symmetry and CISS provide additional control parameters.300                   applications,315 among other technologies.316−318 While differ-
The spin transistor exhibits nonlinear drain-source currents,                 ent device geometries for CPL detectors exist,319−321 the general
with multilevel controlled states generated by the magnetization              working principles are the same; namely, a photoactive layer that
of the source. Varying the source magnetization enables a six-                responds differently under incident left and right circularly
level readout for the two-terminal device.                                    polarized light is used to convert an optical signal into an
   6.1.2. Spin-Optoelectronics. Optoelectronics refers to                     electrical response. The anisotropy factor in circular dichroism,
devices and systems in which light affects the electronic                     gCD, is thus considered a good proxy for determining the
properties of materials and vice versa.301,302 The basic idea of              effectiveness of a photoactive material within a device. Quite
spin-optoelectronics is to control an electrical or photoresponse             surprisingly, however, the responsivity of hybrid organic−
by the spin degree of freedom, in addition to the charge.303−306              inorganic perovskite CPL detectors was found to greatly exceed
CISS enables new design elements for use in optical memory,                   that of gCD.322,323 The origin of the enhancement was initially
electroluminescence, and detection of circularly polarized light.             attributed to the CISS effect,322,324 and then later confirmed
   6.1.2.1. Optical Switching. Optical gating opens the                       upon determining the spin-filtering properties of chiral perov-
possibility to realize simple magnet-free spin valves operating               skites.
under ambient conditions and controlled by photon absorption.                    The CISS-promoted CPL detection proceeds as follows: (i)
Because of CISS, the spin-polarized photocurrent can drive spin               excitation of the photoactive material with circularly polarized
accumulation and the emergence of photocontrolled magnet-                     light, clockwise or counterclockwise, creates a spin-polarized
ization. Such behavior has been shown to manifest in                          electron−hole pair, “Up” or “Down”, because of conservation of
perovskites97 and II-VI quantum dots.118 For instance, a nine-                angular momentum325,326 (ii) electron transport from the
state readout was achieved by using a double quantum dot                      photoexcited material to the electrode exhibits differences in the
architecture, i.e., two different sized quantum dots, on the active           resistivity for spin “Up” and spin “Down” carriers, owing to the
area of a Ni-based Hall sensor.167 In addition, light driven                  CISS effect,327,328 and (iii) the resistivity differences give rise to
changes in molecular configuration have been demonstrated for                 electrical responsivity differences in the device. A growing
changing the spin polarization. Both photoinduced and                         number of researchers, studying various photoactive materials,
thermally induced geometric changes have been used to drive                   are now attributing enhanced CPL detection to CISS-mediated
chirality inversion of a molecular motor, which leads to                      spin-polarized transport.169,329−333 While the generalized
corresponding changes in spin polarization and acts as a                      mechanism holds for photodiode configurations, in which the
molecular spin switch.307−309                                                 charge carrier transport is out-of-plane, it is less clear what extent
   6.1.2.2. Circularly Polarized Electroluminescence. One                     CISS contributes when charge transport is in-plane, e.g., a
approach to the improvement of a circularly polarized light                   photoconductor configuration. Vardeny and co-workers argue
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that for 2D hybrid organic inorganic perovskites in-plane                     sensitive and coherent magnetic sensor, may provide coherent
transport is dominated by Rashba splitting of the electronic                  signatures of an acceptor moiety’s polarization.88 For example,
bands,179 because the CISS effect is maximized when transport                 subnanosecond photoinduced electron transfer in donor−
occurs along the primary chirality axis of the material.                      acceptor DNA hairpin systems produced an entangled spin
Conversely, Wang and co-workers contend that CISS-generated                   qubit (radical pair) at 85 K.365 These results demonstrate that
spin transport still contributes to the response.334 Note that the            pulsed-EPR methods can be used to manipulate coherent spin
electrical transport in a phototransistor is also in-plane; however,          states, which is essential for quantum gate operations. In other
researchers have shown that a device architecture, which uses a               studies, optical excitation of chiral QD systems generates
heterojunction (a chiral hybrid organic−inorganic metal halide                coherent delocalization and charge separation of the exciton on a
interfaced with single wall carbon nanotubes), displays CISS.181              short time scale.120,366,367 While a number of important basic
   6.1.3. Superconducting Spintronics. The idea of “super-                    science questions and technological obstacles remain, the above
conducting spintronics”335−337 has emerged out of the discovery               examples illustrate that chiral materials and structures are
that the spin-singlet Cooper pairs of a conventional super-                   capable of generating quantum effects in realistic solid-state
conductor can be converted into spin-triplet pairs in the                     devices.
presence of ferromagnetic materials with specific forms of                       6.1.5. Future Directions. Hybrid chiral molecule−mag-
magnetic inhomogeneity.338−341 Whereas spin-singlet Cooper                    netic systems encapsulate the notion of molecular technology
pair correlations oscillate rapidly in phase and decay over a very            for the realization of spintronic and chiral spin−orbitronic




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short length scale (of a few nm) in ferromagnetic materi-                     device concepts,368 such as local control over magnetic
als,342−346 spin-triplet pair correlations can propagate over much            properties, as well as chiral spin structures and dynamics.369
longer distances. These spin-triplet pairs carry a net spin                   This connection could bring together two separate fields, both
polarization, hence the name “superconducting spintronics”.                   exhibiting chiral symmetries, and lead to novel functionality,
These facts imply that superconductor/ferromagnetic/super-                    including control of chiral spin textures by chiral molecule
conductor Josephson junctions constructed from conventional                   adsorption, particularly in 2D magnets, where interfacial effects
spin-singlet superconductors can support spin-polarized super-                are maximized.370,371
currents through several tens of nanometers in a strong                          Chiral Magnetic Structures: Skyrmions. The combination of
ferromagnetic material347,348 and over many hundreds of                       chiral structure with chiral magnetism,296 which enables
nanometers through a “half-metallic ferromagnet”, because of                  ultimately stable spin structures such as skyrmions, is potentially
the absence of spin-flip scattering processes.349,350 The field of            a key enabler for applications. On a fundamental science level,
superconducting spintronics, in which two apparently compet-                  the interactions between chiral molecules and chiral magnetic
ing notions of singlet-pairing superconductivity and spin-                    systems are not well understood. Beyond the basic science,
polarized currents are merged, is still in its infancy. To date,              control over these interactions with electrical gates may lay the
most devices consist of multiple sputtered or epitaxially grown               foundation for future applications, such as chiral magnetic
ferromagnetic layers in contact with singlet, s-wave super-                   devices.
conducting electrodes.                                                           Antiferromagnets. The use of antiferromagnets is an
   The CISS effect offers a new paradigm for superconducting                  emerging memory technology, but is notoriously hard to
spintronics, in which chiral molecules induce the required                    control and read.372 To enhance information densities, it may
triplet-pair superconductivity, or assist in its formation when               be possible to combine the CISS effect with antiferromagnets so
integrated within superconductor-ferromagnetic heterostruc-                   that magnetic bits do not repel each other and therefore can be
tures. Chiral imprinting has been demonstrated in both                        densely packed.373 It may be possible to control chiral
semiconductors351−356 and metals.357−360 The adsorption of                    antiferromagnets using current through chiral oxide structures
chiral molecules on conventional singlet-pairing s-wave super-                that filter the desired spin states. The readout of the device may
conductors cause a change in the order parameter of the                       be achieved in a standard two terminal device.
superconductor with signatures of triplet superconductivity,                     Local Magnetic Gradients. By combining electrical gating
with either even-frequency p-wave or odd-frequency s-wave                     and imprinting of local magnetization at the domain size scale,
symmetries.119,228,229,361,362 In superconducting spintronics                 one can create local magnetization profiles with large gradients.
CISS can be utilized to manipulate the conventional s-wave                    Realizing large magnetic-field gradients is important in magnetic
Bardeen−Cooper−Schrieffer superconductors with total spin                     resonance imaging and quantum control,374 where the
zero of the Cooper pairs to become an unconventional s or p-                  information is encoded via the magnetic-field gradient.
wave spin-triplet triplet superconductors with nonzero total                     Integrating such skyrmion-based spintronic/orbitronic ele-
spin. Theoretical studies on ferromagnetic-superconductor and                 ments with chiral-induced triplet superconductors forming
chiral molecule:superconductor hybrid systems have been                       coherent interconnects may reduce heat dissipation in devices
reported also.363                                                             and thus help solve one of the major problems in data
   6.1.4. Quantum Spintronics. Chiral materials are continu-                  processing.
ing to garner attention for their importance to fundamental                      Photovoltaics. Efficient charge separation is a fundamental
research in quantum matter. The high spin selectivity for                     cornerstone of many photovoltaic and photochemical processes,
nanometric chiral films should enable coherent transport, and                 such as artificial photosynthesis, photoelectrochemical water
the strong spin-exchange interactions of chiral molecules with                splitting, and solar fuel production. The CISS effect breaks the
magnetic substrates could lead to new ways of controlling spin                symmetry for electron and hole transport with a certain spin and
polarization by electrical or optical gates.364 Experimental                  can therefore be leveraged for improving charge separation. For
studies into the quantum nature and spin phase of CISS                        instance, Peer et al. employed quantum dots (QDs) and helical
materials and CISS-based device structures can be probed by                   monolayers of chiral L-polyalanine to develop a device that
EPR methods, and maybe NMR experiments (see Section                           achieves efficient charge separation at sub-5 nm length scales
2.4.2).89 EPR experiments, which exploit a qubit as a highly                  without the need for doping.120 A related effect was measured in
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Figure 13. Enantiospecific adsorption of polyalanine (PAL). (a) The micrographs show the adsorption of the PAL oligopeptide [shown in inset of
panel v] on ferromagnetic substrates magnetized with the magnetic dipole pointing Up (H+) or Down (H−) relative to the substrate surface. To
visualize the adsorption, SiO2 nanoparticles were attached to the adsorbed oligopeptides. Panels i and ii show L-PAL and panels iii and iv show D-PAL
adsorbed for 2 s on a substrate magnetized Up or Down. Panel v summarizes the nanoparticle adsorption densities shown in panels i−iv, compared
with the adsorption density on Au with the same applied external magnetic field (red bars). Double-headed arrows represent error bars, the standard
deviation among 10 measurements conducted on each of the 10 samples, hence a total of 100 measurements. b Panel i shows the CD spectra of a
racemic solution of PAL, obtained following exposure to a ferromagnetic substrate with magnetization pointing Down (red) or Up (blue). Following
the adsorption onto the ferromagnetic surface, it is evident that the solution becomes enantioenriched. The line width reflects the uncertainty of the
results. Panel ii shows the CD spectra of the pure enantiomers for comparison. The figure is adapted from ref 21 with permission. Copyright 2018
American Association for the Advancement of Science.

chiral diodes emitting circularly polarized light.375 It is                    fully explored, researchers suggest that the two phenomena
important to note that drawing on these advances, efficient                    could coexist constructively to increase spin polarizations in
photovoltaics could be achieved if the challenge of extending                  chiral materials.39,389 Because continued progress in magneto-
chirality-driven charge separation would be extended to larger                 electric multiferroics necessitates new approaches for creating
scales. The large distance achieved in photoinduced charge                     materials with tailored electronic and magnetic properties, a
transfer processes mediated by chiral molecules376 point to the                CISS-based approach could prove fruitful.
potential of this approach.                                                    6.2. Enantioseparations/Enantiomeric Resolution
   Magnetoelectric Multiferroics. The development of magne-
toelectric multiferroic materials is of great technological                    A significant contribution to the relation between magnetism
importance for advanced electronics applications.377,378 The                   and chirality was discovered by demonstrating an enantiose-
field of “multiferroics” embodies materials that simultaneously                lective interaction of chiral molecules with a magnetized
exhibit two or more ferroic orderings, e.g., ferromagnetism,                   substrate.21 The enantio-discrimination is mediated by a spin-
ferroelectricity, ferroelasticity, and ferrotoroidicity.379 The term           specific interaction, not by the magnetic field itself. The spin-
“magnetoelectric” refers to the coupling between ferroelectric                 dependent charge reorganization observed in chiral molecules
and magnetic order parameters;380,381 more specifically, the                   implies that the interaction between a chiral molecule and a
tuning and switching of an electrical polarization in a material by            magnetized surface should be enantiospecific. Consider a
an applied magnetic field is called a direct magnetoelectric effect,           ferromagnetic metal that is magnetized along its surface normal
and the inverse behavior, tuning and switching of a magnet-                    so that the spin sub-bands of the conduction electrons are split in
ization with an applied electric field, is called the converse                 energy�presenting more filled orbitals of one spin direction
magnetoelectric effect. 382 Multiple reports have shown                        and more empty orbitals of the other spin direction. Because of
emergent ferromagnetism57,92 as well as ferroelectric proper-                  the metal’s spin-dependent orbital population, the chemisorp-
ties383−385 in chiral materials, with the latter proposed to occur             tion or physisorption of a molecule depends on whether the
through either a spin-polarized current mechanism386 or inverse                molecule’s orbitals have a preferred spin direction with respect
Dzyaloshinskii−Moriya interactions (DMI).387,388 Note that,                    to the metal. For example, the interaction energy for a molecule
while the relationship between DMI and CISS has not yet been                   forming a chemisorption bond with a metal spin−orbital will
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depend on whether the spins are aligned antiparallel or parallel.                binding mode heterogeneity at high pH could explain why the
For achiral molecules, the charge redistribution in the molecule                 polarization decreases to zero. Control experiments on n-acetyl
as it approaches and binds to the surface is not spin-dependent                  L-cysteine methyl ester, in which the carboxylate and amine are
and no apparent spin specificity is expected. Conversely, a chiral               protected and presumably do not interact with the substrate, do
molecule approaching the surface undergoes a spin-dependent                      not show this same inversion in polarization with pH (see Figure
charge redistribution, which is enantiospecific, i.e., if the spin               14b). In addition, recent DFT calculations indicate that
makeup in the orbital prefers antiparallel spins, one enantiomer                 adsorbate−solvent interactions may be important for defining
will interact favorably; however, spin−spin repulsion will occur                 the enantiospecificity in adsorption.221 The idea of geometric
with the other enantiomer.                                                       properties controlling spin selectivity could also be responsible
   It is commonly assumed that recognition and discrimination                    for the differences observed in magneto-driven enantioselective
of chirality, both in nature and in artificial systems, depends                  crystallization of racemates (see section 6.2.2). Additional
solely on charge and spatial effects, i.e., shape. However, the                  studies that determine the adsorbate geometry and preferential
CISS effect correlates charge redistribution in chiral molecules                 facet for crystal growth may contribute to a better understanding
with an enantiospecific electron spin orientation, so that                       of enantioselective crystallization.
magnetic surfaces should be enantiospecific when spin                               6.2.2. Crystallization. The spin-exchange interactions that
polarized. Ghosh et al. first showed the enantioselective                        define the preference of magnetized ferromagnetic surfaces for
interaction of chiral molecules with a ferromagnet that was                      one enantiomer over the other can also be leveraged in




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magnetized perpendicular to its surface.21 Here, one enantiomer                  crystallization processes for chiral resolution. It is possible to use
adsorbed preferentially when the magnetic dipole was pointing                    magnetic surfaces to provide a chiral bias for enantiomer specific
Up, whereas the other enantiomer adsorbed faster for the                         amino acid crystallization. Interestingly, studies show that L-
opposite magnetization orientation (see Figure 13). The                          glutamic acid, L-threonine, and D-asparagine preferentially
interaction was not controlled by the magnetic field per se,                     crystallize on North magnetized ferromagnetic substrates
but rather by the electron spin orientations. These studies
                                                                                 despite the asparagine being the opposite enantiomeric form
illustrate the prospects for a new approach to enantiomeric
                                                                                 of glutamic acid and threonine.392 Racemic mixtures of
separations.
                                                                                 asparagine and glutamic acid hydrochloride could thus be
    6.2.1. Enantiospecific Adsorption. Quartz crystal micro-
                                                                                 sorted into enantioenriched conglomerates through crystalliza-
balance measurements by Lu et al. show that the asymmetry in
adsorption kinetics on North and South magnetized ferromag-                      tion in a bath comprising North and South magnetized
netic electrodes is sensitive to the binding orientation.23 Figure               ferromagnetic substrates.392 Conversely, racemic mixtures of
14a shows data in which the pH was systematically changed and                    threonine could not be resolved under the initial solution
                                                                                 conditions because twinning of the enantiomorphs occurs upon
                                                                                 crystallization. These results highlight the limitations of the
                                                                                 CISS-mediated crystallization approach to materials that form
                                                                                 enantiopure crystallites. Despite the nonideal crystallization
                                                                                 properties of threonine, improvements to the apparatus design
                                                                                 and solution conditions led to an enantiomeric excess of ∼60%
                                                                                 in subsequent studies.393 Note that the improved design has the
                                                                                 added benefit of being applicable for bulk crystal separation
                                                                                 through the continuous separation of chiral conglomerate
                                                                                 crystals.393 In addition to asparagine, glutamic acid, and
                                                                                 threonine, chiral resolutions of imeglimin and ribo-aminooxazo-
                                                                                 line have also been performed.393,394
                                                                                    6.2.3. Future Directions. Because of the CISS effect,
                                                                                 magnetic materials offer viable new strategies for enantiosepara-
                                                                                 tion; however, the commercialization of CISS-based separation
Figure 14. Studies into the effect of solution pH on the asymmetry in
                                                                                 systems will require large improvements in the enantioresolu-
effective adsorption rate constant of cysteine onto a magnetized                 tion. To this end a 2-fold approach must be taken. First, efforts
ferromagnetic substrate with a North and South applied magnetic field.           must be made to understand and predict the spin-exchange
Panel A shows the results of L-cysteine (green) and D-cysteine (purple)          interactions that dictate the enantiospecificity. As shown in
adsorbates; panel B shows the results for n-acetyl L-cysteine methyl             EQCM measurements,23,221 the exchange interactions will
ester. The figure is adapted from ref 23 with permission. Copyright              inevitably rely on molecule-dependent structural features that
2021 American Chemical Society.                                                  can change with solution and pH. Second, we must define design
                                                                                 parameters to optimize and control, much like what has been
the polarization in adsorption kinetics, P = (kads,N ′    − kads,S
                                                             ′ )/                done in traditional separation platforms, for efficient separa-
(k′ads,N + k′ads,S), for L-cysteine (green) and D-cysteine (purple)              tions. Initial efforts have been undertaken in this regard for
was measured. Consider the case for L-cysteine: at pH 8, a large                 crystallization systems393 and the groundwork for CISS-column
positive polarization (33%) was observed; however, increasing                    chromatography is currently underway.395
the pH to 8.56 caused a dramatic decrease in the polarization                       Note that CISS separations need not be a standalone
(−15%) before asymptotically approaching a zero polarization                     technology. For instance, the flow cell geometry used during
at even higher pH. The transition from high to low polarization                  the initial discovery of the effect,21 can be coupled with existing
occurs approximately at the pKa of the sulfur moiety on                          flow cell apparatuses that rely on differences between homo and
cysteine390 and previous experiments have shown that this                        heterochiral materials for enantioseparation. Indeed, studies
coincides with a change in molecular binding geometry.391 Large                  show that CISS operates in these conditions and can be as
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Figure 15. Proposed mechanistic scheme to explain the role of CISS during water splitting. Panel a shows a model lattice where the color of the ball
indicates the spin of a radical intermediate adsorbate on the catalyst (shown here as a hydroxyl); blue indicates a spin down site whereas red indicates a
spin up site. For chiral catalysts (left) the electrons at adjacent sites are spin aligned, because of the spin polarization, and thus formation of triplet
oxygen is favored. For achiral catalysts (right) spin disorder exists and often necessitates either a change in spin state or a singlet-mediated pathway for
the reaction to proceed. The figure is adapted from ref 299. Copyright 2020 American Chemical Society. Panel b shows the influence of the solution pH
conditions on this process. For achiral catalysts a larger potential (+E) is needed to overcome the spin disorder limitations, compared to chiral catalysts,
and additional singlet reaction pathways become more prominent. Panel c shows a theoretical treatment to determine the free energy of oxygen
evolution at each reaction step on a CoFe2O4(111) surface toward triplet oxygen with (red) and without (blue) spin alignment on the catalyst surface.
This figure is adapted from ref 421 with permission (http://creativecommons.org/licenses/by/4.0/).

strong, if not stronger than, the stereoisomeric interac-                         apparent; not only was spin polarization responsible for
tions.116,222                                                                     decreasing the reaction overpotential for the OER, it was
6.3. Chemical Reactions                                                           shown to inhibit the formation of hydrogen peroxide, as well as
                                                                                  other super oxides.406 These effects have since been shown for
Electron spin plays a critical role in chemical bonding, and the                  other chiral catalysts,407−413 including chiral metal ox-
manipulation of spin in reactive processes by the CISS effect                     ides117,193,133,414−416 and metal sulfides.183,184 As an aside, we
offers a new strategy for controlling reaction pathways. This                     note that CISS may account, in part, for the high activity of
promise has been demonstrated for water electrolysis with chiral                  photosystem II.417
electrocatalysts (see Section 6.3.1), and it offers a general                        Although chiral ligands improve OER efficiency, they can
strategy for improving selectivity in reaction mechanisms that                    reduce the density of active sites on the catalyst surface. To
involve intermediates of different spin multiplicity. More than                   circumvent these issues chiral CuO thin films, which do not
this, CISS implies that the electron spin is coupled to the                       contain chiral molecules, were fabricated and show a similar
molecular frame of a chiral molecule (or material) and affords an                 improvement in the OER compared to achiral controls.41 Here,
ability to translate control over the electron spin into control                  the chirooptically active CuO gives rise to spin polarization, as
over enantioselectivity. We discuss the initial steps along this                  measured by Mott polarimetry;39,41 however, all other measured
pathway in Section 6.3.2. Realization of CISS in chemical                         properties of the achiral and chiral catalysts were the same, e.g.,
reactions is driving a paradigm shift in how we view chemical                     XPS spectra, absorbance, etc. Later works with chiral CuO/Ni-
synthesis.                                                                        foam,418 cobalt oxide,299 molybdenum sulfide,184 and iron−
   6.3.1. CISS Enhances Efficiency of O2 Reactions. CISS                          nickel composites419 have shown similar improvements in the
can improve the efficiency of the oxygen evolution reaction                       electrolysis over the achiral analogues. Figure 15 shows a
(OER) and oxygen reduction reaction (ORR), which remain                           proposed mechanism to explain how spin polarization affects the
important bottlenecks for numerous electrocatalytic and                           overpotential and Faradaic efficiency of the reaction as a
electrochemical processes, including water electrolysis,396                       function of pH.299 Experiments show that the Faradaic efficiency
exchange membranes for batteries and fuel cells,397−401 and                       for OER with achiral (reaction 3 in Figure 15b) and chiral
the electrochemical reduction of CO2,402,403 among others.404                     catalysts (reaction 1 in Figure 5b) are similar at high pH values,
   6.3.1.1. Oxygen Evolution Reaction (OER). The first work to                    which is consistent with unfavorable formation of hydrogen
improve the efficacy of the OER with CISS used photoanodes                        peroxide, pKa1 of 11.7 for the hydroxyl radical.420 A large
comprising quantum dots assembled on chiral molecules to                          difference in reaction overpotential was still observed, however,
lower the overpotential for the OER and to generate larger                        and was associated with a spin flip being required to form the
quantities of hydrogen at the cathode than analogous photo-                       triplet oxygen. As the pH decreases the difference in over-
anodes coated with shorter chain achiral molecules.405 The                        potential persists, but now the reaction intermediates comprise
effect was attributed to the spin polarization on the photoanode                  both hydroxyl radicals and oxy radicals. For achiral catalysts
favoring the ground state formation of triplet oxygen O2 (3∑−g )                  (reaction 4 in Figure 15b), in which spin constraints are not
and these findings were later corroborated with photoanodes                       present, this leads to a lower Faradaic efficiency because of the
comprising conductive polymers.145 In subsequent studies with                     competition with hydrogen peroxide formation. Conversely for
helically aggregated dye molecules158 additional features of spin                 chiral catalysts (reaction 2 in Figure 15b), the formation of the
polarization on the characteristics of water splitting became                     singlet-mediated byproduct is spin forbidden and therefore the
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Figure 16. Linear sweep voltammograms for oxygen reduction in O2-saturated 0.1 M KOH solutions using electrodes coated with achiral (a) and chiral
(b) SAMs. The possible spin-mediated O2−substrate interactions available in the case of a chiral catalyst (c) and an achiral catalyst (d). The figure is
adapted from ref 428 with permission.

Faradaic efficiency remains high. These studies indicate that the               now considered indirect evidence for spin polarization arising
effect of spin polarization on the OER becomes increasingly                     from the CISS effect.117,299
important as the pH decreases to neutral and acidic conditions.                    6.3.1.2. Oxygen Reduction Reaction (ORR). Chiral-induced
Figure 15c shows an alternative mechanism in which the free                     spin selectivity has also been shown to improve the efficiency for
energy associated with each step of the catalytic cycle, toward                 the oxygen reduction reaction. Sang et al. showed that gold
the production of triplet oxygen, is proposed to change if the                  electrodes coated with alkanethiol SAMs exhibit progressively
catalyst is spin polarized (red) or not (blue).421                              higher overpotentials with increasing alkane chain length,
   A common approach to predicting the performance of a                         whereas the opposite trend was observed with chiral SAMs
heterogeneous catalyst uses the Sabatier principle in the form of               comprising oligopeptides: the overpotential decreased for
a “volcano” plot. For the OER, workers often plot the negative of               increasing peptide length (see Figure 16).428 The effect was
the overpotential versus the difference in the Gibbs energy of the              attributed to spin alignment of the chiral electrode surface
adsorbed oxy and hydroxy radical intermediates on different                     lowering the transition state energy for reduction of the triplet
electrocatalysts, so that the apex gives the optimum condition                  oxygen for chiral catalysts (Figure 16c) compared to achiral
for the reaction.422,423 Recent work on NiOx and Fe(3−x)CoxO4,                  catalysts in which the spin alignment at adjacent sites on the
two catalysts near the apex of the volcano for the OER, suggest                 catalyst is less favorable (Figure 16d). To test the viability of
                                                                                CISS for more relevant catalyst systems, the authors extended
that chirality manifests as an independent design variable that
                                                                                the study to include chiral platinum nanoparticles and compared
can be used to reduce overpotential.133,416 The difference in
                                                                                the results to commercially available platinum on carbon black, a
overpotential between chiral and achiral catalysts has been
                                                                                common benchmark material. The chiral catalysts showed
explained in theoretical works as spin polarization modulating                  marked improvement in both mass activity and specific activity
the transition state energies of the reaction intermediates                     over the platinum carbide catalyst.428 The effect of spin
compared to catalysts that are not spin polarized.424−426 The                   polarization on ORR efficiency has since been shown in other
change in energies associated with spin polarization can be so                  works.429,430
extreme that even the OER rate-determining step can change.                        6.3.2. Organic Electrosynthesis. CISS is promising in
Ren et al. showed such behavior for magnetized achiral                          facilitating organic reactions and promoting enantioselectivity
ferromagnetic catalysts,421 and Vadakkayil et al. showed that                   through spin control. As discussed in Section 6.2, the charge
CISS-mediated spin polarization from chiral Fe(3−x)CoxO4                        polarization of a chiral molecule is accompanied by a spin
catalysts can accomplish the same.416 Concomitant with the                      polarization20 and this process can lead to enantiospecific
change in rate-determining step, the chiral Fe(3−x)CoxO4                        interactions between chiral molecules and ferromagnetic
catalysts displayed extraordinary mass activity, on par with                    substrates.21 The same enantiospecific interactions have been
some of the largest reported in the literature and >400-fold                    leveraged in electrochemical reactions to facilitate the reduction
higher than benchmark IrO2 catalysts under the same electro-                    (or oxidation) of one enantiomer while inhibiting that of the
lytic conditions.427 Improvement in OER characteristics for                     other. Enantiomeric enrichment of a racemic solution through
chiral metal oxide catalysts over analogous achiral catalysts is                CISS-mediated electrochemistry was first demonstrated for the
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Figure 17. Electrochemical quartz crystal microbalance measurements of the electropolymerization of R,R-EDOT (a) and S,S-EDOT (b) onto a
ferromagnetic electrode with a North (red) or South (blue) applied magnetic field. Panel c shows an experimental scheme illustrating differences in the
spin-exchange interactions between the chiral monomers and the magnetization state of the electrode giving rise to differences in the nucleation step of
the reaction. The figure is adapted from ref 434 with permission. Copyright 2020 American Chemical Society.

reduction of camphorsulfonic acid to 10-mercaptoborneol.24                      cycloaddition reaction of 2,3-dimetylbutadiene with acetalde-
Magnetizing a ferromagnetic electrode with a North (South)                      hyde to form 2,3,5-trimethyl-2,6-dihydro-2H-pryan. 433
magnetic field, applied normal to the electrode surface-plane,                  Although the enantiomeric excess in these studies are small,
causes the irreversible reduction of S-camphor sulfonic acid to                 they demonstrate the remarkable capabilities of CISS in
proceed more (less) readily than R-camphorsulfonic acid. This                   chemical synthesis.
asymmetry leads to a time-dependent increase in the                                6.3.3. Polymerization. The CISS effect has also been
enantiomeric excess of camphorsulfonic acid, in which the                       shown to operate during electropolymerization reactions on
enantiomer that appears in excess is determined by the applied                  magnetized ferromagnetic electrodes. For instance, profilometry
magnetic field. Subsequent measurements on the same redox                       measurements following the electropolymerization of 2,3-
reaction show that the enantioselectivity of the ferromagnetic                  diphenyl-3,4-ethylenedioxythiophene (EDOT) monomers for
electrode decays, by ∼33%, upon prolonged reaction con-                         a fixed amount of charge showed that the thickness of R,R-
ditions.431 X-ray photoelectron spectroscopy analysis attributed                EDOT films under an applied South magnetic field (116 ± 5
the behavior to electrode fouling and degradation, arising from                 nm) was greater than that of a North magnetic field (80 ± 5 nm).
sulfur formation at the electrode surface, and highlights the                   Conversely, the opposite was true for the S,S-EDOT monomers;
importance of establishing methods to stabilize the electrode,                  North applied magnetic field (120 ± 5 nm) was greater than
and hence its polarization, for enantioselective electrochemistry.
                                                                                South magnetic fields (90 ± 5 nm).434 Note, under both
Chiral metal surfaces, such as nickel, are also being used to
                                                                                magnetizations the films were thicker than the case when a
resolve racemic mixtures.432
                                                                                magnetic field was not applied, indicating increased mass
   Other work shows that spin-mediated catalysis, and CISS-
based phenomena, can be used to electrochemically transform                     transport associated with magnetohydrodynamic effects;435
achiral materials into enantioenriched chiral products. For                     however, the change in thickness with field orientation is a
instance, magnetized ferromagnetic electrodes coated with                       manifestation of CISS. The results were further corroborated by
Fe2O3 catalysts convert methylphenylsulfide, under oxidative                    EQCM measurements, which showed that the electropolyme-
conditions, to chiral methylphenylsulfoxide.433 Here, applica-                  rization of the R,R-EDOT monomer (Figure 17a) was faster
tion of a North magnetic field gave rise to an 8.5% enantiomeric                when the ferromagnetic electrode was magnetized South (blue)
excess, whereas a South magnetic field produced a 16%                           and slower when a North (red) magnetic field was applied, and
enantiomeric excess of the other enantiomer. The authors                        for the S,S-EDOT monomer (Figure 17b) was faster when a
argue that spin alignment of the reactant at the magnetized                     North (red) magnetic field was applied compared to a South
electrode surface places symmetry constraints on the reaction,                  (blue) magnetic field. Figure 17c shows an experimental scheme
such that the transition state energy for the formation of the two              rationalizing the differences in thickness to changes in the spin-
different enantiomers of the product is no longer degenerate.                   exchange interactions between the chiral monomers and
Using the same electrode configuration, the authors further                     magnetized ferromagnetic electrodes during the nucleation
demonstrate CISS-based enantioenrichment for a Diels−Alder                      step of the polymerization.
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   In addition to affecting the polymerization of chiral                      low enantiomeric excess. While chiral resolution and enantio-
monomeric units, the CISS effect can aid in controlling the                   selective synthesis remains an attractive application of CISS-
handedness of polymers composed of achiral monomers, so long                  based ideas, experiments necessitate improvements in the
as the polymer can adopt a helical geometric structure. Initial               enantiomeric excess to garner interest for applications. To
studies demonstrated this phenomenon for the electropolyme-                   achieve high product enantiopurity, studies will likely rely on a
rization of achiral 1-pyrenecarboxylic acid monomers onto                     combination of traditional methods for asymmetric catalysis,
ferromagnetic substrates, in which the application of a North                 such as a chiral medium or chiral electrode,448,449 in tandem with
and South magnetic field gave rise to opposite circular dichroism             the CISS effect. The CISS effect may also find use for other
spectra for the resulting polymer.24 In subsequent studies a                  classes of reactions. For instance, radical and radical-pair
similar phenomenon was observed using carbazole, 3,4-                         mechanisms are argued to be influenced by CISS�either
ethylenedioxythiophene, and 2-vinylpyridine monomers.150,431                  directly, through coherence or polarization effects involving
Electropolymerization with 2-vinylpyridine monomers is                        chiral molecules,88,450 or through indirect processes as a result of
particularly interesting, as the spin polarization emanating                  fields generated from a chiral catalyst surface. It has long been
from the ferromagnetic electrode created an enantiopreference                 shown that magnetic fields can affect reactivity and reversibility
for the generation of carbon stereocenters in the polymer                     of reactions involving correlated spins451 and therefore CISS
chain.150 Although a mechanism for how chirality emerges in                   ought to imbue analogous behavior. While experimental
systems with achiral monomeric units has not yet been realized,               evidence for CISS-mediated organic catalysis involving a




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one possible explanation relies on the CISS effect and spin-                  radical-pair mechanism is minimal, previous theoretical and
dependent charge polarization.431 Because the monomers are                    experimental studies imply the existence of said reactions in
achiral, at early reaction time, electropolymerization likely                 nature.89,139,452,453 Moreover, a recent study suggests that the
results in a mixture of right-handed and left-handed short chain              coherent relation between electrons is important in redox
oligomers. However, as the reaction proceeds, delocalization of               reactions involving transfer of multiple-electrons.430 This
the spin-polarized electrons from the substrate into the                      subject is in its infancy and work must be performed for
oligomers would depend on the enantiomeric form, and hence                    understanding and establishing the effect for successful
a spin selectivity preference of the oligomer should emerge. Such             utilization in chemistry.
behavior would cause differences in the reactivity of the two                 6.4. Role of CISS in Biology
enantiomers and thus favor the formation of one enantiomer
over the other in a manner that depends on the orientation of the             Biomolecules and biopolymers in living organisms are largely
applied magnetic field.                                                       homochiral, i.e., they appear almost exclusively in one
   6.3.4. Future Directions. Despite substantial progress,                    enantiomeric form. Many workers have considered the origin
much work remains to control and exploit CISS in chemical                     of homochirality and its function; however, it remains an open
reactions. In related work on the effect of spin constraints on               question. Given its recent discovery, CISS has not been part of
reaction pathways, spin alignment through the application of an               this scientific conversation; however, new experiments, which
external magnetic field has been shown to guide the carbon                    are described below, argue that it should be.
dioxide reduction reaction toward more value-added prod-                          6.4.1. Biological Redox Processes. The study of
ucts,436−438 as well as improve nitrogen fixation,439,440 hydro-              bioenergetics is the study of protein and substrate redox
genation of ethylene,441 and Fenton chemistry,442 among                       chemistry. Although proteins may at first seem an odd choice for
others.404,443,444 Such systems thus represent a viable testbed               redox chemistry, their amino acid properties and organization,
of reactions for which CISS studies can be performed. It is                   which can significantly impact local cofactor environments,
important to stress that there are added benefits to replicating              provide a way to control the energetics of redox reactions. Yet,
the magnetic field effect studies using chiral catalysts beyond just          these benefits do not require homochirality. The benefits arising
reiterating that spin-constraints affect reaction activity: (i) the           from CISS do provide a fundamental rationale for nature to
spin polarizations can be much higher in chiral materials, >99%,              choose homochiral biopolymers, i.e., proteins for electron
than that found in magnetized ferromagnets, (ii) CISS affords                 transfer. Numerous in vitro studies show that electron transfer in
additional flexibility on catalyst design, allowing one to impart             proteins, and their complexes, are spin polarized (see Section
spin effects to state-of-the-art catalysts without being limited by           3.1.2). Recent protein voltammetry studies of cytochrome c,
the catalyst’s magnetic properties; and (iii) additional details              immobilized on chiral tripeptide monolayer films, reveal the
regarding the mechanism can be learned by comparing                           importance of the electron spin and the film’s homochirality on
magneto- vs CISS-catalysis. In addition to spin mediated effects,             electron transfer kinetics.58 This study shows rate constant
application of an external magnetic field during electrolysis can             asymmetries as large as 60% and reveal marked differences in the
also affect mass transport435,445 and have been credited by some              average electron transfer rate constant for homochiral
for the improved activity during the carbon dioxide reduction                 assemblies, in which the peptide and protein possess the same
reaction.446,447 A comparison of the activity between chiral and              enantiomeric form, compared to heterochiral assemblies, where
achiral catalysts, in which mass transport effects do not occur,              the handedness of the peptide layer is opposite to that of the
could help better elucidate the role of spin in the reaction                  protein, or is heterochiral itself. Because of the CISS effect and
mechanism. Ultimately the efficacy of CISS in bulk electrolysis               its resultant coupling of the linear momentum of the electron to
will depend on many factors such as the stability of the catalyst             its spin, the backscattering of electrons (which would require
during electrolysis, the scalability of the approach, as well as the          both electron-vibration coupling and a spin flip) is inhibited so
ease at which the materials can be incorporated into existing                 that the fidelity of electron transfer over long ranges is facilitated.
constructs.                                                                       6.4.2. Role of Electron Spin on Protein Stability. A
   With the exception of Diels−Alder cycloaddition studies,433                recent study has examined the importance of spin-exchange
the effect of CISS on organic transformations has been limited to             interactions on protein stability. After luciferase enzymes were
one electron reduction, or oxidation, reaction steps and shows                adsorbed onto paramagnetic and ferromagnetic nanoparticles in
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solution, their denaturation upon addition of urea was                      shown that phototriggered charge injection from a site-specific
examined.232 The enzymes structural stability was assessed                  ruthenium photosensitizer into the protein phosphoglycerate
using two methods: bioluminescence measurements, which                      kinase (PGK) increases its binding with an antibody by 2-fold
monitored the activity of the Luciferase enzyme, and fast                   and suppresses the enzymatic activity of PGK by a factor as large
spectroscopy, which detected the distance between two                       as three.466 Moreover, these responses are elicited by excitation
chromophores implanted at the termini of a barnase core. For                with left (but not right) circularly polarized light, i.e., injected
both measurements, interactions with magnetic materials                     electrons spin matters, presumably because of spin-filtering by
altered the structural and functional resiliency of the natively            the protein’s chiral structure. This work reveals the possibility of
folded proteins, showing greater stability on ferromagnetic                 controlling a protein’s binding and enzymatic activity through
surfaces than on paramagnetic surfaces, under mild denaturing               circular polarized light and/or by attaching chiral entities at a
conditions. The phenomenon was attributed to differences in                 point remote to the protein’s active site.
the spin-exchange interactions involved in the magnetic                         6.4.5. Origin of Life. The origin of symmetry breaking and
imprinting properties of each type of nanoparticle and was                  the rise of homochiral organisms from a “primordial chemical
supported by additional measurements on proteins at macro-                  soup” has long intrigued scientists. Because of the prevalence of
scopic magnetic surfaces. The results imply a link between                  amino acids and DNA in early CISS studies, the idea that the
internal spin-exchange interactions in a folded protein and its             electron spin could affect biological processes is long-stand-
structural and functional integrity on magnetic surfaces; or more           ing.467 The discovery that the electron spin can act as a chiral




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broadly, spin-exchange interactions should be considered as                 bias to enantiospecifically facilitate chemical reactions,24,431
additional factors governing protein structure.                             however, has brought forth new deterministic hypotheses for the
   6.4.3. Biomolecular Interactions and Recognition.                        emergence and persistence of homochirality in Nature. For
Molecular interactions are essential in biology; however,                   instance, Ozturk and Sasselov proposed that CISS could act as a
understanding the strength of the interactions, and/or their                symmetry breaking agent in cyanosulfidic prebiotic chemistry,
specificity, typically relies upon a more general knowledge of the          which is hypothesized to give rise to some of life’s most
thermodynamics, dynamics, and structural components of the                  important molecular building blocks.468 Primordial reactions
interacting species.454,455 Commonly, however, the bioaffinity              such as these are conjectured to occur in shallow lake basins
that is measured in recognition processes is higher than those              known to contain magnetite and have previously been identified
calculated by available methods.456−459 Using spin-exchange                 as favorable geological locations to facilitate the origin of
microscopy methods, a direct measurement of the interaction                 life.469,470
force between two chiral peptides showed a difference in force of              It is important to note that a large enantiomeric excess in
∼70 pN between homochiral and heterochiral peptide−peptide
                                                                            initial reactions is not necessary to eventually achieve
interactions.116 These findings were further supported by
                                                                            homochirality, multiple autocatalytic471−473 and nonlinear
calculations using a simple theoretical model, which found
                                                                            processes474,475 could occur that increase enantiopurity over
that the spin-mediated interactions among peptides in close
                                                                            time. In addition, CISS-mediated processes could also act to
proximity was stronger than that of hydrogen bonding. Note
                                                                            reinforce and propagate homochirality in biology. Studies have
that a model with better quantitative agreement to the data was
achieved by incorporating dispersion interactions and spin-                 shown that spin-exchange interactions between chiral RNA
exchange interactions.460 EQCM methods have also been used                  precursors and magnetized magnetite can direct enantiospecific
to probe the effects of electron spin on biomolecular exchange              crystallization; achieving homochirality, i.e., 100% enantiomeric
interactions, showing that both the thermodynamic driving                   excess, from a racemic mixture in two steps.394 Moreover,
force as well as the dynamics for adsorption are affected.222               studies have shown that spin alignment in homochiral
Interestingly, the enantiospecificity of the adsorption did not             assemblies affords more efficient energy transduction than that
correlate with the handedness of the interacting substituents, but          in heterochiral analogs, providing another rationale for Nature’s
instead with the sign of the Cotton effect in the circular                  preference to be homochiral.58
dichroism spectra associated with the interacting moiety.                       6.4.6. Future Directions. The emergence of life on earth is
Collectively, these studies imply that the CISS effect can be               reported to date back as far as ∼3.7 billion years,476 and Nature
just as important in biomolecular interactions and recognition              has undergone considerable evolutionary change. Biology, as we
events as traditional stereoisomeric and thermodynamic                      know today, manifests highly organized structures on multiple
considerations.                                                             length scales that gives rise to elegant functions. As such, leaning
   6.4.4. Allosteric Interactions. The transfer of information              on life’s years of evolutionary optimization in physical and
through biomolecules to induce binding or initiate reactions at             chemical processes to provide innovation and solutions for
remote sites, is a defining principle in biological chemistry and           modern applications can be advantageous and is referred to as
chemical biology.461 Yet, the fundamental mechanism(s)                      biomimicry.477 A greater understanding of the intricacies that
underlying information transfer through the several nanometers              define biological processes is thus paramount, and the discovery
typical for cell membranes and proteins remains an open                     of CISS may help to further elucidate subtle features in biology,
question. Protein function may be modulated by the binding of a             as well as improve existing biotechnologies. For instance,
small ligand or another protein, a familiar phenomenon termed               incorporation of spin polarization in bioelectronic mimetics may
allostery. Studies show that allostery can be mediated by a                 increase the specificity and sensitivity of biorecognition
conformational change or by a change in a protein’s                         elements in sensors. Indeed, CISS-based sensing platforms are
dynamics.462−465                                                            beginning to be developed.59,61,105,478,479 Moreover, the living
   Because modulation of a protein’s polarizability can affect its          cell can be viewed as a miniaturized information processor or
function, spin effects can become important. It was recently                computer; cells input information through intermolecular
demonstrated that charge redistribution, and hence spin                     interactions, use proteins for intracellular communication, and
polarizations, affect allostery.22 In subsequent work, it was               store information as DNA. The cell performs these tasks more
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effectively than conventional computers.480 Does the spin                    of replacing methods for asymmetric catalysis by spin-polarized
information afforded through CISS contribute to this efficiency?             electron sources. This subject has enormous scientific and
                                                                             industrial potential, and effort should be devoted to its
7. CRITICAL ASSESSMENT OF THE FIELD                                          exploration. In addition, the role of CISS in molecular biology
                                                                             and its promise for developing new methods for controlling
The field of CISS has grown rapidly in the past decade,                      protein activity could be profound. Preliminary studies of CISS
advancing in many directions. The basic CISS observation, the                in biology have been conducted when the systems are anchored
presence of different electron currents through chiral structures            to ferromagnetic substrates, and it will be important to extend
when one of the contacts is magnetic and the magnetization is                this work to more realistic conditions and to studies in vivo.
switched, has been observed by a variety of research groups                  Molecules are “quantum devices”, and although it is natural to
worldwide. In addition, the CISS effect is observed over a large             explore the possible role of chiral molecules in quantum
range of temperatures and manifests for single molecules, for                information science (QIS), this field is nascent. The ability to
monolayers, for thin films, and in bulk crystals. Theoretically,             create materials that show quantum properties at room
several viable mechanisms have been proposed to explain these                temperature is very appealing for QIS, and CISS offers a new
phenomena, and an important emphasis in the short term will be               approach to this end. Discovered in 1999, CISS remains a
to validate a mechanism experimentally�be it one of those                    scientific adolescent whose promise is high, but remains to be
proposed or some combination thereof.                                        realized.
   A clear discrepancy exists between the experimental state of




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the field and the theoretical one. Experimentalists have a fair
                                                                             AUTHOR INFORMATION
ability to predict, qualitatively, what to expect from their
experimental setups and are using this ability to focus their                Corresponding Authors
studies on addressing questions that can support the theory                     Brian P. Bloom − Department of Chemistry, University of
developments, exploring the implications of CISS to other fields                  Pittsburgh, Pittsburgh, Pennsylvania 15260, United States;
of study, or developing CISS-related applications. Basic                            orcid.org/0000-0001-9581-9710; Email: bpb8@pitt.edu
questions like the effect of the substrate and of a chiral                      Yossi Paltiel − Applied Physics Department and Center for
molecule’s SOC on the spin selectivity, the temperature                           Nano-Science and Nano-Technology, The Hebrew University
dependence of CISS, the role of spin currents and angular                         of Jerusalem, Jerusalem 9190401, Israel; orcid.org/0000-
momentum currents, and quantum CISS effects are now being                         0002-8739-9952; Email: paltiel@mail.huji.ac.il
studied. Other experimental efforts are examining the role of                   Ron Naaman − Department of Chemical and Biological Physics,
CISS in other research domains, including spin-controlled                         Weizmann Institute, Rehovot 76100, Israel; orcid.org/
chemistry, biological processes, spintronics, and quantum                         0000-0003-1910-366X; Email: ron.naaman@
information.                                                                      weizmann.ac.il
   The situation is very different when one considers the                       David H. Waldeck − Department of Chemistry, University of
theoretical efforts to explore the mechanism of CISS. It is now                   Pittsburgh, Pittsburgh, Pennsylvania 15260, United States;
clear that all attempts to obtain quantitative agreement between                    orcid.org/0000-0003-2982-0929; Email: dave@pitt.edu
calculations and experiments by using one electron models have
failed. Theoretical approaches that go beyond the single electron            Complete contact information is available at:
Hamiltonian are being developed and show promise. They can                   https://pubs.acs.org/10.1021/acs.chemrev.3c00661
reproduce major portions of the experiments and solve some of
the issues raised in relation to time reversal symmetry and the              Notes
Onsager principle. A major challenge for theory is to develop ab             The authors declare no competing financial interest.
initio methods that include these “beyond single electron”
concepts in order to open the way toward predicting                          Biographies
experimental results in advance. Concepts that are important                 Brian Bloom obtained his B.Sc. in Chemistry and B.A. in Physics from
to include in theoretical models are the electrons’ spin and                 Duquesne University in 2009, and his Ph.D. in Chemistry from the
charge polarization, phonons/vibrations, and wave function                   University of Pittsburgh in 2016. He stayed at the University of
entanglement.                                                                Pittsburgh following his graduate studies as a postdoctoral researcher
                                                                             from 2016 to 2019, a research associate from 2019 to 2023, and in 2023
8. CONCLUDING REMARKS AND FUTURE OUTLOOK                                     became a research assistant professor. Brian began research on the
Because the linkage of electron spin and the chiral symmetry of              chiral-induced spin-selectivity effect in 2015 and it has since remained
matter was not appreciated during the 20th century, much of our              the primary focus of his research interests.
knowledge is built on information about matter that did not                  Professor Yossi Paltiel earned his B.Sc. in Physics and Mathematics
account for CISS and is often mute on its role. Investigations               from the Hebrew University, and his Master’s and Ph.D. in 2002 from
into CISS promise new insights for various fields, from                      the Weizmann Institute of Science. He then worked both in leading
chemistry and biology to physics. Many of the fundamental                    high-tech industry groups and the Soreq national lab in Israel. Since July
studies are providing a better understanding of CISS; however,               2009, he has led the Quantum Nano Engineering group at the Hebrew
these findings continue to open new avenues of study in other                University, Israel. Paltiel is winner of the 1st place in the Kaye
areas, e.g., emergent magnetism (Section 2.3.2), superconduc-                Innovation Awards 2019 and is a cochair of the 2025 Gordon
tivity spintronics (Section 6.1.3), and the origin of homochirality          conference on Electron Spin Interactions with Chiral Molecules and
in biology (Section 6.4.5). At this stage of research, the                   Materials. Paltiel’s group’s goal is to establish a way to incorporate
ramifications of CISS cannot be fully charted. For instance, the             quantum mechanics into room temperature “classical” devices, through
ability to use the electron’s spin as a “chiral reagent” was                 mimicking Biology and Chemistry processes. The Paltiel group has
demonstrated, but we are far from being able to achieve the goal             worked on spin interfaces using chiral molecules and materials, the

                                                                      1978                                         https://doi.org/10.1021/acs.chemrev.3c00661
                                                                                                                               Chem. Rev. 2024, 124, 1950−1991

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CISS effect, for the last 15 years, and opened a way for both basic                 Zarnecki, J.C. Homochirality as the Signature of Life: the SETH Cigar.
understanding of the effect and its applications. Professor Paltiel has             Planet. Space Sci. 1996, 44, 1441−1446.
published more than 200 papers in leading journals as well as issued 15               (2) Meierhenrich, U. Amino Acids and the Asymmetry of Life: Caught in
patents. Paltiel has two startup companies. The first named Valentis                the Act of Formation; Springer. 2008.
                                                                                      (3) Xiao, W.; Ernst, K.-H.; Palotas, K.; Zhang, Y.; Bruyer, E.; Peng, L.;
Nanotech was founded in 2013. The company utilizes nanocellulose
                                                                                    Greber, T.; Hofer, W. A.; Scott, L. T.; Fasel, R. Microscopic Origin of
unique properties to produce a biodegradable transparent sheet with
                                                                                    Chiral Shape Induction in Achiral Crystals. Nat. Chem. 2016, 8, 326−
additional controlled optical and gas/water barrier properties. The                 330.
second company named Chiral Energies was founded in 2022 and aims                     (4) Lee, T. D.; Yang, C. N. Question of Parity Conservation in Weak
to enhance green energy production by using chiral coatings. Group                  Interactions. Phys. Rev. 1956, 104, 254−258.
web page: https://www.qnelab.com/.                                                    (5) Ray, K.; Ananthavel, S. P.; Waldeck, D. H.; Naaman, R.
Ron Naaman earned his B.Sc. in 1973 from Ben-Gurion University of                   Asymmetric Scattering of Polarized Electrons by Organized Organic
the Negev and his Ph.D. in 1978 from the Weizmann Institute of                      Films of Chiral Molecules. Science 1999, 283, 814−6.
                                                                                      (6) Carmeli, I.; Gefen, Z.; Vager, Z.; Naaman, R. Alternation Between
Science, Israel. He worked as a postdoctoral researcher at Stanford
                                                                                    Modes of Electron Transmission through Organized Organic Layers.
University in California, and later spent a year in the Department of               Phys. Rev. B 2003, 68, 115418.
Chemistry at Harvard University. In 1981, he joined the faculty of the                (7) Ray, S. G.; Daube, S. S.; Leitus, G.; Vager, Z.; Naaman, R.
Weizmann Institute in the Department of Isotope Research (later                     Chirality-induced Spin-selective Properties of Self-assembled Mono-
renamed the Department of Chemical Physics). From 1989 to 1995,




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                                                                                    layers of DNA on Gold. Phys. Rev. Lett. 2006, 96, 036101.
Naaman chaired the Institute’s Chemical Services Unit, and from 1995                  (8) Carmeli, I.; Skakalova, V.; Naaman, R.; Vager, Z. Magnetization of
to 2000 he headed the Department of Chemical Physics. From 2008 to                  Chiral Monolayers of Polypeptide: a Possible Source of Magnetism in
2010, Naaman was the Chair of the Scientific Council at the Institute.              Some Biological Membranes. Angew. Chem., Int. Ed. Engl. 2002, 41,
He was awarded the Kolthof Prize from the Technion, the excellent                   761−4.
research prize from the Israel Vacuum Society and from the Israel                     (9) Wei, J. J.; Schafmeister, C.; Bird, G.; Paul, A.; Naaman, R.;
Chemical Society, the Chirality Medal in 2023, the Israel Chemical                  Waldeck, D. H. Molecular Chirality and Charge Transfer Through Self-
Society Golf Medal, and the Humboldt-Meitner award. He serves as an                 assembled Scaffold Monolayers. J. Phys. Chem. B 2006, 110, 1301−8.
                                                                                      (10) Xie, Z. T.; Markus, T. Z.; Cohen, S. R.; Vager, Z.; Gutierrez, R.;
associate editor for PCCP. Ron Naaman is a Fellow of the American
                                                                                    Naaman, R. Spin Specific Electron Conduction through DNA
Physical Society, Fellow of the Royal Society of Chemistry, and
                                                                                    Oligomers. Nano Lett. 2011, 11, 4652−4655.
Member of Academia Europaea. He has published more than 350                           (11) Aragones, A. C.; Medina, E.; Ferrer-Huerta, M.; Gimeno, N.;
scientific papers. Currently his research is focused on the chiral-induced          Teixido, M.; Palma, J. L.; Tao, N.; Ugalde, J. M.; Giralt, E.; Diez-Perez,
spin selectivity effect that his group discovered.                                  I.; Mujica, V. Measuring the Spin-Polarization Power of a Single Chiral
David Waldeck obtained a B.Sc. in Chemistry from the University of                  Molecule. Small 2017, 13, 1602519.
Cincinnati in 1978 and a Ph.D. in Chemistry from the University of                    (12) Göhler, B.; Hamelbeck, V.; Markus, T. Z.; Kettner, M.; Hanne, G.
Chicago in 1983. He was a postdoctoral fellow at the University of                  F.; Vager, Z.; Naaman, R.; Zacharias, H. Spin Selectivity in Electron
                                                                                    Transmission through Self-assembled Monolayers of Double-stranded
California, Berkeley from 1983 to 1985, where he held an IBM
                                                                                    DNA. Science 2011, 331, 894−7.
Postdoctoral Fellowship. In 1985 he moved to the University of                        (13) Naaman, R.; Waldeck, D. H. Chiral-Induced Spin Selectivity
Pittsburgh where he has remained. David chaired the Chemistry                       Effect. J. Phys. Chem. Lett. 2012, 3 (16), 2178−2187.
Department at Pittsburgh from 2005 to 2014, and he has been the                       (14) Evers, F.; Aharony, A.; Bar-Gill, N.; Entin-Wohlman, O.;
Academic Director of the Petersen Institute of Nanoscience and                      Hedegard, P.; Hod, O.; Jelinek, P.; Kamieniarz, G.; Lemeshko, M.;
Engineering at Pittsburgh since 2015. David was the Belkin Visiting                 Michaeli, K.; Mujica, V.; Naaman, R.; Paltiel, Y.; Refaely-Abramson, S.;
Professor at the Weizmann Institute, Israel in 1998, and won the ISE                Tal, O.; Thijssen, J.; Thoss, M.; van Ruitenbeek, J. M.; Venkataraman,
Bioelectrochemistry Prize in 2018. He is a fellow of the American                   L.; Waldeck, D. H.; Yan, B.; Kronik, L. Theory of Chirality Induced
Physical Society, the American Chemical Society, and the American                   Spin Selectivity: Progress and Challenges. Adv. Mater. 2022, 34,
Association for the Advancement of Science. David’s research and                    No. e2106629.
teaching expertise is in physical chemistry. Throughout his research                  (15) Kettner, M.; Göhler, B.; Zacharias, H.; Mishra, D.; Kiran, V.;
career he has used spectroscopic and electrical measurement methods                 Naaman, R.; Fontanesi, C.; Waldeck, D. H.; Sek, S.; Pawlowski, J.;
                                                                                    Juhaniewicz, J. Spin Filtering in Electron Transport Through Chiral
to study molecular systems in the condensed phase. Currently his
                                                                                    Oligopeptides. J. Phys. Chem. C 2015, 119, 14542−14547.
research is focused on the chiral-induced spin selectivity effect.
                                                                                      (16) Mazin, I. I. How to Define and Calculate the Degree of Spin
                                                                                    Polarization in Ferromagnets. Phys. Rev. Lett. 1999, 83, 1427−1430.
ACKNOWLEDGMENTS                                                                       (17) Liu, T.; Weiss, P. S. Spin Polarization in Transport Studies of
                                                                                    Chirality-Induced Spin Selectivity. ACS Nano 2023, 17, 19502−19507.
D.H.W. and R.N. acknowledge the support from the US                                   (18) Naaman, R.; Paltiel, Y.; Waldeck, D. H. Chiral Induced Spin
Department of Energy Grant ER46430. R.N. acknowledges the                           Selectivity Gives a New Twist on Spin-Control in Chemistry. Acc.
partial support of the AFOSR Grant FA9550-21-1-0418 and the                         Chem. Res. 2020, 53, 2659−2667.
support by a research grant from the Estate of Rena G. Moses                          (19) Ghosh, S.; Mishra, S.; Avigad, E.; Bloom, B. P.; Baczewski, L. T.;
and the Laurie Kayden Foundation. D.H.W. acknowledges                               Yochelis, S.; Paltiel, Y.; Naaman, R.; Waldeck, D. H. Effect of Chiral
partial support from NSF-CHE-2140249 and AFOSR Grant                                Molecules on the Electron’s Spin Wavefunction at Interfaces. J. Phys.
FA9550-23-1-0368.                                                                   Chem. Lett. 2020, 11, 1550−1557.
                                                                                      (20) Kumar, A.; Capua, E.; Kesharwani, M. K.; Martin, J. M.; Sitbon,
                                                                                    E.; Waldeck, D. H.; Naaman, R. Chirality-induced Spin Polarization
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