"Inherently Chiral" Electrode Surfaces and Media: Alternative Approaches to Enantioselective Electrochemistry

The ability to select among different electroactive molecules, or among different redox centers on a single molecule, in both analytical and synthetic applications, is a typical asset of electrochemistry, based on fine control of the electrode potential, possibly enhanced by the choice of appropriate electrode surfaces and media. An attractive step further, of great fundamental and applicative interest, is represented by enantioselective electrochemistry, implying the ability to discriminate the enantiomers of chiral molecules in terms of electrode potentials (in electroanalysis), or to selectively activate or achieve a given enantiomer of a chiral molecule through the electrode potential (in electrosynthesis). Since the enantiomers of a chiral molecule have identical physico-chemical properties and therefore the same electrochemical behaviour except when interacting with some other chiral entity, enantioselective electrochemistry necessarily implies the electron transfer process to take place in asymmetric conditions. This can be achieved by the use of either a chiral electrode surface or a chiral medium. Among the many approaches so far proposed for this ambitious target along either of the two possible ways, a groundbreaking strategy was recently proposed [1], based on the use of "inherently chiral" molecular materials, either as electrode surfaces [2-5] or as media [6]. The peculiarity of inherently chiral molecular materials is that the same element endows the molecule with both its key functional property and with chirality, coinciding with the main molecular backbone featuring a tailored torsion; this results in outstanding chirality manifestations. Thus, electrooligomerization of enantiopure inherently chiral electroactive monomers, based either on biheteroaromatic atropoisomeric cores combined with thiophene-based wings or on thiahelicene scaffolds, yields enantiopure inherently chiral electrode surfaces, on which impressive peak potential differences are observed in voltammetric experiments for the antipodes of chiral probes, even quite different in structure and electrochemical reactivity.[1-5] At least one of the monomers can even yield self-standing inherently chiral artificial membranes. Large differences in peak potentials can also be achieved for the enantiomers of different chiral probes working on achiral electrodes, but in suitable inherently chiral media. For instance, inherently chiral ionic liquids ICILs have been prepared from atropoisomeric 3,3′-bicollidine, resolved into antipodes without chiral HPLC and converted into long-chain dialkyl salts with melting points below room temperature. Both the new ICILs and shorter family terms that are solid at room temperature, employed as low-concentration additives in achiral ionic liquids, result in impressive peak potential differences, regularly increasing with additive concentration, for the enantiomers of different probes on achiral electrodes. [6] Work is in progress along both of the above lines to strengthen and rationalize the first proofs of concepts by developing, characterizing and testing a wider variety of inherently chiral inductors (both monomers for electrode surface preparation and ionic liquids/additives), with different chiral probes, particularly of pharmaceutical interest, with more optimized and detailed protocols, and with the support of theoretical computations; other possible applications of the new inductors are also being considered. A selection of the most interesting recent achievements will be presented and discussed. The support of Fondazione Cariplo/Regione Lombardia "Avviso congiunto per l’incremento dell’attrattività del sistema di ricerca lombardo e della competitività dei ricercatori candidati su strumenti ERC - edizione 2016” (Project 2016-0923) is gratefully acknowledged. References: [1] Angew Chem. Int. Ed. 53 (2014) 2623. [2] Chem. Eur. J. 20 (2014), 15298. [3] Chem. Sci., 6 (2015) 1706. [4] Anal. Bional. Chem., 408 (2016) 7243. [5] Chem. Eur. J. 22 (2016) 10839. [6] Angew Chem. Int. Ed., 56 (2017) 2079.