Strategies for High Enantioselectivity at Electrode Surfaces: Implementing Inherent Chirality in Electroactive Thin Films or Electrode|(Ionic Liquid) Interfaces

Chiral electroanalysis could be regarded as the highest recognition degree in electrochemical sensing, implying the ability to discriminate between specular images of a given electroactive molecule in terms of significant peak potential difference. Since enantiomers have identical physico-chemical properties, the electron transfer process must take place in asymmetric conditions, exploiting a suitable chiral selector, such as a chiral electrode or a chiral medium. A groundbreaking strategy was recently proposed, based on the use of inherently chiral molecular selectors, either electrode surfaces1 or media2. Inherent chirality implies the chirality source of the chiral selector to be neither localized nor external, but intrinsic to the whole main molecular backbone, featuring a tailored torsion; this can result in outstanding chirality manifestations. Thus, large differences in peak potentials have been observed for the enantiomers of different chiral probes: (a) working on inherently chiral electrode surfaces consisting of thin electroactive oligomer films1 (often including macrocycle terms) electrodeposited from enantiopure inherently chiral monomers of different architectures, with either dissymmetric elements (dibenzothiophene, bithiophene or biindole atropoisomeric cores), or asymmetric elements (helicenes); (b) working on achiral electrodes, implementing inherent chirality in their interphase with an ionic liquid medium,2 exploiting the latter's peculiarly high order. To this aim we developed inherently chiral ionic liquids ICILs as double salts of an atropoisomeric 3,3′-bipyridine scaffold with long alkyl chains and a suitable anion, resulting in melting points below room temperature. However, we found it even more convenient to employ the new ICILs as well as other family terms solid at room temperature as low-concentration chiral additives in commercial achiral ionic liquids: impressive peak potential differences, regularly increasing with additive concentration, have been observed for the enantiomers of different probes on achiral electrodes. Comparable results have also been obtained with other inherently chiral additives (bibenzimidazolium double salts and a helicene derivative). 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 selectors (both surfaces 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, particularly aiming to the recognition mechanism elucidation.