Achieving chiral electroanalysis on achiral electrodes in innovative "inherently chiral" media

Recently we have presented "inherently chiral" electrodes of unprecedented enantiorecognition ability, able to both discriminate (in terms of large potential differences) and quantify (in terms of linear dynamic ranges for currents) the enantiomers of many chiral probes, without need of prior HPLC separation [1]. The electrode surfaces consist of heterocycle-based "inherently chiral" electroactive oligomers, mostly cyclic, with extraordinary chirality manifestations [2,3]. The "inherent chirality" concept implies that chirality does not originate from localized or external sources, but the stereogenic element responsible for chirality (a tailored torsion induced by atropisomeric biheteroaromatic scaffolds) coincides with the entire main conjugated molecular backbone. To achieve chiral electroanalysis, an alternative strategy to using chiral electrodes is to work on achiral electrodes but in a chiral medium. Chiral ionic liquids CILs should perform much better than chiral organic solvents, on account of their much higher intrinsic order; and, by analogy with the electrode case, "inherently chiral" ionic liquids ICILs should perform even better than CILs. To obtain ICILs and test our assumption, we envisaged that the bis-onium salts of atropisomeric biheteroaromatic nitrogen-containing scaffolds could satisfy the “inherent chirality” requirements. The best example we found so far is an alkylated bipyridine scaffold, 3,3'-bicollidine (Fig.1). Consisting of two moieties separated by a very high torsional barrier, it exists in two stable enantiomers that can be separated and stored. The high torsional barrier also results in low overall conjugation efficiency, with first oxidation and reduction located near or beyond the background, ensuring a very wide potential window (a desirable feature for use as electrochemical reaction medium). The bicollidine scaffold can be converted by alkylation into (di)alkyl salts. The number and length of the alkyl chains, as well as the anion choice, modulate the melting points; according to the latter being higher or lower than room T, the new salts can be used as inherently chiral ionic liquids or/and inherently chiral supporting electrolytes. 3,3'-Bicollidine is particularly advantageous also because its enantiopure antipodes can be obtained by fractional crystallization of diastereoisomeric salts, without requiring expensive preparative HPLC; this allows to obtain enantiopure ICILs and inherently chiral supporting electrolytes by an affordable route. Two bicollidinium ICILs have been already obtained, and we are now scaling their synthesis to achieve suitable quantities for tests as enantioselective media. However, in the meanwhile, considering that shorter-chained terms in the series, of easier synthesis, could also be of high interest as inherently chiral supporting electrolytes, as well as provide a first proof-of-concept of the family enantioselectivity requiring much smaller amounts of the chiral inductor, we have tested enantiopure (R)- and (S)-3mE2BF4 antipodes as low-concentration chiral additives in achiral ionic liquid BMIMPF6. The test was performed on commercial SPEs, with the same commercial (R)- and (S)- ferrocenyl-based probes previously used for analogous tests of inherently chiral surfaces. The result was an outstanding enantiomer separation (Fig. 2, about 250 mV with 0.01 M chiral additive in BMIMPF6). We also observed that enantiomer separation is modulated by the additive concentration, and that the medium enantioselectivity holds even changing the nature of the chiral probe, or in the simultaneous presence of different probes. Such an extraordinary result, beyond our own expectations, points to the possibility to obtain outstanding enantiodiscrimination on achiral electrodes employing the new compounds even as minority components in a commercial achiral medium. References [1] F. Sannicolò, S. Arnaboldi, P.R. Mussini et al. Angew. Chem. Int. Ed. 53, 2014, pp 2623-2627. [2] F. Sannicolò, P.R. Mussini, S. Arnaboldi et al. Chem. Eur. J. 20, 2014, pp 15298-15302. [3] S. Arnaboldi, P.R. Mussini, F. Sannicolò et al. Chemical Science 6, 2015 pp. 1706-1711.