The CISS effect was firstly identified by Naaman and coworkers in 1999, who determined the scattering asymmetry in electrons transmission in Langmuir-Blodgett films made of L- and D-stearoyl lysine (Ray et al., 1999). Their results showed that the quantum yield of photoelectrons depended both on the relative polarization of the light, and the chirality of the molecules. They started the study of the main factors that influence the CISS effect using self-assembled monolayers (SAMs) of double-stranded (ds) DNA and oligopeptides, demonstrating that spin selectivity is correlated to the supramolecular organization of single molecules, and its magnitude increases with the length of the DNA strands or peptide sequence, respectively (Carmeli et al., 2002; Ray et al., 2006; Göhler et al., 2011; Xie et al., 2011; Kettner et al., 2015; Aragonès et al., 2017; Kiran et al., 2017; Tassinari et al., 2018; Torres-Cavanillas et al., 2020). These studies pointed out the previously ignored role of the spin in electron-biomolecule interactions, as well as the potential of SAMs of chiral molecules that work as spin filters at room temperature (Michaeli et al., 2016; Naaman et al., 2019).

Several theoretical models have been described to explain the spin-selective transport through chiral molecules, using helical-shaped molecules and dsDNA (Guo and Sun, 2012; Gutierrez et al., 2012; Medina et al., 2012). The first models found in literature share two important features: chirality is essential to reach spin polarization, and a helical potential based on the Rashba-like SOC term needs to be considered to calculate the SO interaction (Naaman and Waldeck, 2012). Later on, Dalum and Hedegard suggested a novel mechanism for CISS based on perturbative approach calculations, that need to be concretized to specific systems (Dalum and Hedegård, 2019). First-principle calculations were used by Gutierrez and coworkers to study the geometry-dependent spin polarization using an atomistic model of oligoglycine. The helical symmetry displayed a much higher spin polarization than the β-strand conformation, highlighting the role of helical geometry in the CISS effect (Maslyuk et al., 2018). In this sense, Herrmann et al. analyzed the crucial role of the imaginary terms in the Hamiltonian matrix for nonvanishing spin polarization in helical structures (Zöllner et al., 2020).

Furthermore, recent studies remark the important role of phonons and polarons to reach high spin polarization. Fransson showed the importance of cooperation of electron-phonon and spin-dependent couplings to get an exchange splitting between the spin channels that is reasonable for CISS (Fransson, 2020). In particular, he investigated systems of chiral molecules coupled to metals, where molecular vibrations (phonons) represent a mechanism able to break the spin symmetry of the molecule (Fransson, 2021). On their side, Zhang et al. assessed spin polaron transport in chiral molecules and, unlike previous theoretical explanations, their results showed that both type of polarons (spin-up and spin-down) can traverse the chiral molecule, although with different spin dynamics, i.e., the ones with antiparallel orientation experiment spin switching (Zhang et al., 2020).

Overall, there is not a general consensus as of now that theoretically rationalizes the astounding value experimentally observed for the CISS effect. Nevertheless, the investigations mentioned above suggest several reasons to explain this effect that range from the buildup of spin polarization at the interface to the electron-phonon interactions and polaron transport, and very recently, to the topological orbital texture combined with SOC in the substrate (Liu et al., 2021).Further theoretical investigations are currently ongoing that are expected to give more insights into these theoretical points.

There are multiple experimental methods to investigate the CISS effect (Naaman and Waldeck, 2015). Photoelectron spectroscopy has been used to characterize spin orientation through a SAM of chiral molecules adsorbed in a gold substrate when irradiating with circularly polarized light. The spin of the transmitted electrons is detected using a Mott polarimeter (Göhler et al., 2011). Conductive-probe atomic force microscopy (cp-AFM) is another technique that measures the spin-dependent conduction through single molecules (Xie et al., 2011; Kettner et al., 2015; Bullard et al., 2019). With this technique, the current-voltage (J-V) curves are registered on a SAM of chiral molecules adsorbed on a ferromagnetic substrate (normally nickel), while gold nanoparticles are attached to the tail of some of these molecules. It can be considered one of the best techniques to evaluate the real spin selectivity as it does not detect electrons from non-covered areas of the surface.

Spin polarization Hall devices measure Hall voltage and cyclic voltammetry response on chiral SAMs (Kumar et al., 2017; Bullard et al., 2019). The sign of the observed Hall voltage depends on the chirality of the molecule.

Recently, a technique that combines time-resolved microwave conductivity (TRMC), electron paramagnetic resonance (EPR) and optical spectroscopy has been used to study charge carrier mobility and spin state in p-type semiconductors (Tsutsui et al., 2018). Chemical doping using iodine vapors generates radicals that allow to determine the species with different spin state present in the sample.

Since the identification of the CISS effect, big efforts have been made to understand it in a wide variety of molecular systems, including biologically relevant molecules as DNA and peptides (Naaman and Waldeck, 2015). Only recently, several key parameters in spin polarization and its magnitude have been disclosed. The dependence of spin selectivity on the molecular length was demonstrated by varying the number of amino acid residues in oligopeptide sequences using cyclic voltammetry (Figure 2A) and cp-AFM (Kettner et al., 2015; Kiran et al., 2017), finding that spin selectivity decreases when increasing the tip-loading force. Following these studies, Aragonès and coworkers proved current asymmetry in chiral single molecular junctions by scanning tunneling microscopy break-junction (STM-BJ). They used 22-mer L- and D-oligopeptide systems, a magnetized nickel tip and a gold electrode (Aragonès et al., 2017). The spin selectivity in electron transfer was also noted when 12-mer oligopeptides were attached to ferrocene, where oxidation or reduction were favored depending on the L- or D-enantiomer and the direction of the magnetic field (Tassinari et al., 2018). Importantly, a polyproline chiral system (Pro₈) conjugated to zinc porphyrins showed that the spin-polarized generated currents were further transmitted over distances surpassing the length of chiral molecules (Bullard et al., 2019). Very recently, ds peptide nucleic acids (PNAs) have been proposed to study the CISS effect. Their spin-filtering capabilities were directly correlated to the molecular helicity, highlighting the worth of the dsPNAs for systematic studies of the CISS effect (Möllers et al., 2021).

The helical structure of dsDNA is very attractive in spintronics because it has played a critical role in charge transport processes through long molecular distances (Kiran et al., 2017). In 2011, Göhler and collaborators presented the first example of spin filters based on DNA. They obtained spin polarization exceeding 60% at room temperature measured by Mott polarimetry with dsDNA monolayers adsorbed on gold (Göhler et al., 2011). Densely packed single stranded (ss) and dsDNA films with a redox-active probe adsorbed on a gold-capped nickel surface were analyzed by cyclic voltammetry. Only the dsDNA films displayed variations of up to 16% in the electrochemical reduction depending on the orientation of the magnetic field. This states that the chiral supramolecular organization prevails over the chirality of the individual components (Zwang et al., 2016). The linear dependence of the spin polarization on the length of dsDNA oligonucleotides has also been demonstrated by cp-AFM using lengths of 20 up to 50 base pairs (Mishra et al., 2020a) (Figure 2B). Later, Banerjee-Ghosh et al. proved experimentally that there is an enantiospecific interaction between chiral molecules and perpendicularly polarized substrates. They followed the kinetics of the enantioselective adsorption of dsDNA on a magnetized Ni/Au surface, finding that the rate of absorption was considerably different for up and down magnetization of the substrate (Banerjee-Ghosh et al., 2018). Additionally, researchers have investigated the effect of oxidative damage on the spin transport through monolayers of dsDNA using a Hall device (Bullard et al., 2019). Unexpectedly, dsDNA having one and two oxidative damages in the base pairs had higher spin polarization than undamaged dsDNA films. It seems that due to the damage of the bases most of the conduction goes through the backbone of the DNA structure, which is chiral and hence, more spin selective.

Helicenes are fully conjugated molecules without stereogenic carbons. The repulsion between the termini of these molecules makes the helicenes adopt permanent helical conformations with M (left-handed enantiomer) and P (right-handed enantiomer) configurations (OuYang and Crassous, 2018). Kiran et al. have shown that cationic [4] helicenes behaved as spin filters when they were uniformly absorbed and oriented on a pyrolytic graphite surface (Kiran et al., 2016). Spin polarizations of more than 40% were obtained with preferred opposite spin orientation for P and M configurations. In another report, monolayers made of enantiopure [7] helicenes were deposited on Cu (332), Ag (110), and Au (111) surfaces, which have a wide range of SOC values (Kettner et al., 2018). Very similar results of spin selectivity were obtained, proving the dominant role of chirality in the spin filtering ability of helicenes over the SOC of the surfaces. Interestingly, some authors have pointed out improved charge transport properties on racemic mixtures of helicenes compared to enantiopure composition in organic electronic devices (Yang et al., 2017). Important morphological differences between the racemic and enantiopure systems were found, as well as an 80-fold increase in hole mobility in FETs. On the other hand, Josse et al. compared device efficiency fabricated with enantiopure and racemic naphthalimide end-capped [6] helicenes as electron acceptors (Josse et al., 2017), observing a two-fold increase in electron mobility, and a five-fold increase of the power conversion efficiency in devices fabricated with the enantiopure material compared to the racemic. These contradictory results emphasize the need to further investigate the impact of solid-state organization in chiral supramolecular systems in organic electronic devices. In 2019, it was presented for the first time the change of spin selectivity by modifying the handedness of chiral molecules by external stimuli (Suda et al., 2019) (Figure 2C). An artificial molecular motor based on an overcrowded alkene was synthesized. It was able to switch its chirality generating a unidirectional rotation cycle driven by temperature or light, with spin selectivity values of up to 44%.

Chirality has been demonstrated crucial for spin filtering also in different polymers and π-conjugated molecules, as for example in organic light emitting diodes (OLEDs). Thanks to the CISS effect, chiral polymers represent a great alternative for spin polarization and injection with high spin selectivity. For instance, thin films of thiophene-based polymers incorporating cysteine exhibited high spin filter ability at room temperature, as shown using a solid-state device to determine magnetoresistance and electrochemical measurements (Mondal et al., 2015). Another intriguing example illustrating the importance of selective spin transport in supramolecular structures is the improvement in water splitting by avoiding the formation of hydrogen peroxide (Figure 2D). In this case, the anode was coated with a helix-forming chiral organic semiconductor that enhanced the desired process thanks to the CISS effect (Mtangi et al., 2017). Later on, the importance of supramolecular chirality rather than the number of chiral centers present in the molecule was demonstrated using coronene bisimide and porphyrin-like polymers with chiral (or achiral) alcoxyphenyl chains (Kulkarni et al., 2020). In principle, supramolecular helicity is expected to be inverted depending on the stereoconfiguration of the chiral centers in the π-conjugated molecule or polymer. However, it was shown that both, M and P chiral helicity can also emerge from a monomer with the same chirality (e.g., L-derivative). In this sense, the secondary arrangement can be inverted by changing the temperature (+20°C or −10°C) (Kulkarni et al., 2020), or by using a different solvent (Mishra et al., 2020b). More recently, spin polarization was identified in achiral polymers with a preferred helical arrangement induced by the use of chiral solvents. The authors used triphenylene-2,4,10-tricarboxamide derivatives, whose supramolecular chirality is biased to get either P- or M-helices when using chiral solvents (Mondal et al., 2021) (Figure 2E). The inversion of supramolecular chirality by means of temperature and solvent when using the same enantiomer affects spin selectivity, and confirms the importance of supramolecular orientation in selective spin transport. In fact, very recently, Meijer and coworkers claimed the pivotal role of chiral supramolecular order rather than the number of chiral centers in discrete molecules in the CISS effect using squarine dyes (Rösch et al., 2021).

Inorganic and hybrid inorganic-organic materials have shown as well properties as spin filters. Hybrid materials of perovskites frameworks integrating a chiral organic sublattice have presented spin selectivity much larger than previously reported in SAM systems (Waldeck et al., 2021). Recently, Lu et al. achieved spin polarizations of up to 86% in oriented R- and S-chiral 2D-layered Pb-iodide hybrid organic-inorganic perovskite (HOIP) films. Weak thickness dependence was displayed in films from 20–100 nm (Lu et al., 2019) In another report, Huang et al. demonstrated that chiral-HOIPs are capable of changing the magnetization of an adjacent NiFe ferromagnetic substrate. The sign of the magnetization studied by Magneto-optic Kerr rotation effect depended on the chirality of the HOIP (Huang et al., 2020). Recently, a spin-polarized LED at room temperature without magnetic or ferromagnetic contacts, which are normally required has been reported (Kim et al., 2021). Furthermore, bioinspired chiral metal-organic Cu(II) phenylalanine (D- or L-) crystals have shown to present CISS electron conduction over long ranges (300 nm) at room temperature measured by magnetic cp-AFM. Interestingly, the authors also reported a thermally activated ferromagnetic behavior, which had only been identified in inorganic materials(Huang et al., 2020).

In 2019 Ghosh et al. prepared copper oxide films capable of spin polarize photoelectrons and act as electrocatalyst for the conversion of water to oxygen. The spin filtering ability of chiral CuO avoids the generation of side products such as H₂O₂ (Ghosh et al., 2019). In another example by the same group, chiral cobalt oxide films used as electrocatalysts in the oxygen evolution reaction achieved a 1.4-fold increase in the production of oxygen(Ghosh et al., 2020).