Electroactive chiral oligo- and polymer layers for electrochemical enantiorecognition

Electronically conducting polymer (ECP) and oligomer films are one of the most popular classes of artificial materials for electrode surface modification and nanostructured electroactive film preparation for use as active layers in advanced sensing electrochemical devices. They can act as both receptors and transducers on account of their electroactivity and easy derivatization in a virtually unlimited structure range, and typically have low cost and easy processability. The tailoring possibilities of ECP films also make them attractive selector candidates to achieve the superior level of molecular recognition represented by enantioselective electroanalysis, implying to discriminate between specular images of a chiral molecule . This superior recognition level requires to endow them with chirality and to employ them as enantiopure films, which can be made along different strategies, with different implications in terms of enantioselectivity, kind of transduction of the recognition event, specificity vs general applicability, preparation difficulty, robustness, etc. In this context an outstanding tool is provided by the \u201cinherent chirality\u201dstrategy

Enantiomer discrimination in absorption spectroscopy and in voltammetry: highlighting fascinating similarities and connections

Absorption spectroscopy and voltammetry, of known analogies and connections, share even more fascinating similarities and connections at a higher complexity level, when "upgrading" them with the ability to discriminate between enantiomers by chiral selector implementation. In both techniques either "molecular" selectors or "electromagnetic" ones (L- versus Rcircularly polarized light components for spectroscopy, ccversus b-spin electrons for voltammetry) can be considered; moreover, external magnetic field application can replace a truly chiral actor. A tentative schematization is provided. Analogies and connections also concern molecular features of the enantiodiscrimination actors. In both techniques outstanding performances are obtained with inherently chiral molecules, in which a conjugated backbone with tailored torsion is source of chirality as well as spectroscopic and electrochemical activity, in an attractive three-fold interconnection. Their outstanding effects can be justified by a combination of chemical and electromagnetic properties (excellent potential molecular spin filters), a fascinating challenge for future developments

One-Dimensional Discrete Stark Hamiltonian and Resonance Scattering by Impurities

A one-dimensional discrete Stark Hamiltonian with a continuous electric field is constructed by extension theory methods. In absence of the impurities the model is proved to be exactly solvable, the spectrum is shown to be simple, continuous, filling the real axis; the eigenfunctions, the resolvent and the spectral measure are constructed explicitly. For this (unperturbed) system the resonance spectrum is shown to be empty. The model considering impurity in a single node is also constructed using the operator extension theory methods. The spectral analysis is performed and the dispersion equation for the resolvent singularities is obtained. The resonance spectrum is shown to contain infinite discrete set of resonances. One-to-one correspondence of the constructed Hamiltonian to some Lee-Friedrichs model is established.Comment: 20 pages, Latex, no figure

2,12-diaza[6]helicene: An efficient non-conventional stereogenic scaffold for enantioselective electrochemical interphases

The new configurationally stable, unsymmetrical 2,12-diaza[6]helicene was synthesized as a racemate and the enantiomers were separated in an enantiopure state by semi-preparative HPLC on chiral stationary phase. Under selected alkylation conditions it was possible to obtain both the enantiopure 2-N-mono- and di-N-ethyl quaternary iodides. Metathesis with bis(trifluoromethanesulfonyl)imide anion gave low-melting salts which were tested as inherently chiral additives to achiral ionic liquids for the electrochemical enantiodiscrimination of chiral organic probes in voltammetric experiments. Remarkable differences in the oxidation potentials of the enantiomers of two probes, a chiral ferrocenyl amine and an aminoacid, were achieved; the differences increase with increasing additive concentration and number of alkylated nitrogen atoms

Helicity: a non-conventional stereogenic element for designing inherently chiral ionic liquids for electrochemical enantiodifferentiation

Configurationally stable 5-aza[6]helicene (1) was envisaged as a promising scaffold for non-conventional ionic liquids (IL)s. It was prepared, purified, and separated into enantiomers by preparative HPLC on a chiral stationary phase. Enantiomerically pure quaternary salts of 1 with appropriate counterions were prepared and fully characterized. N-octyl-5-aza[6]helicenium bis triflimidate (2) was tested in very small quantities as a selector in achiral IL media to perform preliminary electrochemical enantiodifferentiation experiments on the antipodes of two different chiral probes. The new organic salt exhibited outstanding enantioselection performance with respect to these probes, thus opening the way to applications in the enantioselective electroanalysis of relevant bioactive molecules

Highly enantioselective “inherently chiral” electroactive materials based on a 2,2' -biindole atropisomeric scaffold

Chiral oligothiophene monomers with C2 symmetry, based on 3,30 -bithiophene atropisomeric cores with high racemization barriers, have recently been shown to provide excellent chiral starting materials with high electroactivity for the easy preparation of enantiopure electroactive films endowed with powerful chirality manifestations. We now introduce an inherently chiral monomer based on a 2,20 -biindole core, as the prototype of a new inherently chiral monomer family, whose properties could be modulable through functionalization of the pyrrolic N atoms. By fast, regular electrooligomerization the new monomer yields inherently chiral films with high, reversible electroactivity and, above all, impressive enantioselectivity towards very different chiral probes, some of pharmaceutical interest, as generalscope electrode surfaces. Such results, while opening the way to a new, attractive inherently chiral selector class, nicely confirm the general validity of the inherent chirality strategy for chiral electrochemistry. Furthermore, the enantioselectivity of the new selectors not only holds with electroactive chiral probes, but also with circularly polarized light components as well as electron spins, resulting in good chiroptical and spin filter performances, which suggests fascinating correlations between the three contexts

A Simultaneous Discrimination of Two Different Probes on Achiral Electrodes

A Simultaneous Discrimination of Two Different Probes on Achiral Electrodes S. Grecchia, S. Arnaboldia, S. Rizzob, F. Sannicol\uf2a, P.R. Mussinia a Universit\ue0 degli Studi di Milano, via Golgi 19, 20133 Milano, Italy b Istituto di Scienze e Tecnologie Molecolari, CNR, Via Golgi 19, 20133, Milano, Italy [email protected] In literature few studies have dealt with electrochemistry or electroanalysis on achiral electrodes, the selector being provided by the medium, either having a chiral selector dissolved into it or being itself endowed with chirality. More recently, we have decided to implement the \u201cinherent chirality\u201d concept for the development of media to combine the powerful strategy of inherent chirality with the physico-chemical properties of the ionic liquids. Ionic liquids, organic salts with low melting points, are increasingly popular media on account of many peculiar advantageous properties respect to volatile organic solvents (low vapor pressure, chemical and thermal stability, high solvating ability, non-flammability \u2026). They are even more attractive for electrochemical processes, acting as both solvent and supporting electrolyte, and especially featuring an extremely well-ordered structure at the interface with a charged electrode, expanding for many layers, like a semisolid crystal, even in the presence of significant water traces, and modulated by other species possibly present at the interface. Sometimes, they even border with liquid crystals. A high degree of supramolecular organization can induce significant chirality transfer from the medium to the dissolved species. And, analogously to the electrode case, this attitude could be maximized by the \u201cinherent chirality\u201d strategy, that is, working in inherently chiral ionic liquids, ICILs. To implement inherent chirality in ionic liquids, that are usually based on a heteroaromatic cation with at least one long alkyl chain (to lower the melting point), Sannicol\uf2 et al. proposed to start from biheteroaromatic scaffolds, like bipyridine or bibenzimidazole ones. [1] By dialkylation such inherently chiral scaffolds can be converted into the corresponding double salts. With at least one long alkyl chain and a suitable anion, the melting point can be lowered below room temperature; thus, two ICILs have been very recently obtained as enantiopure antipodes, starting from bicollidine, a very convenient scaffold on account of its low-cost synthesis and possibility to be separated into enantiomers by fractional crystallization, without expensive chiral HPLC. Their enantioselectivity was tested as low-concentration additives in achiral commercial ionic liquids on screen-printed electrodes, with chiral probes already used in tests with electrodes modified with inherently chiral surfaces [2]; large, specular enantiomer peak potential differences were observed. Attractively, the same behavior, as chiral additives, was also shown by family terms solid at room temperature, of faster and easier synthesis. In this context we are studying the effect of the chiral additives on two simultaneously present chiral probes, the first of them giving a chemically reversible ET process. We have to assess the experiments on all possible binary and ternary combinations but evidence of simultaneous discrimination apparently emerges. The inherent chirality research is currently supported by Regione Lombardia and Fondazione Cariplo (Avviso congiunto per l\u2019incremento dell\u2019attrattivit\ue0 del sistema di ricerca lombardo e della competitivit\ue0 dei ricercatori candidati su strumenti ERC-edizione 2016, Project 2016-0923). [1] S. Rizzo, S. Arnaboldi, V. Mihali, R. Cirilli, A. Forni, A. Gennaro, A.A. Isse, M. Pierini, P.R. Mussini, F. Sannicol\uf2 (2017) Angewandte Chemie. International Edition, 56, 2079-2082; S. Arnaboldi, R. Cirilli, A. Forni, A. Gennaro, A. A. Isse, V. Mihali, P. R. Mussini, M. Pierini, S. Rizzo, F. Sannicol\uf2 (2015) Electrochimica Acta, 179, 250-262; S. Rizzo, S. Arnaboldi, R. Cirilli, A. Gennaro, A. A. Isse, F. Sannicol\uf2, P. R. Mussini (2018) Electrochemistry Communications, 89, 57-61 [2] F. Sannicol\uf2, S. Arnaboldi, T. Benincori, V. Bonometti, R. Cirilli, L. Dunsch, W. Kutner, G. Longhi, P.R. Mussini, M. Panigati, M. Pierini, S. Rizzo (2014) Angewandte Chemie. International Edition, 53, 2623-2627; S. Arnaboldi, T. Benincori, R. Cirilli, S. Grecchi, L. Santagostini, F. Sannicol\uf2, P.R. Mussini (2016) Analytical And Bioanalytical Chemistry, 408, 7243-7254. S. Arnaboldi, T. Benincori, R. Cirilli, W. Kutner, M. Magni, P. R. Mussini, K. Noworyta, F. Sannicol\uf2 (2015) Chemical Science, 6, 1706-171

Chiral biobased ionic liquids with cations or anions including bile acid building blocks as chiral selectors in voltammetry

Chiral ionic liquids (CILs), or ionic liquids (ILs) with chiral additives, are very attractive chiral media for enantioselective electroanalysis, on account of their high chiral structural order at the electrochemical interphase. A family of molecular salts with CIL properties is now introduced, based on the chiral steroid building block of deoxycholic acid implemented either in the anion or cation. Testing them as chiral additives in a commercial achiral IL, they enable voltammetric discrimination of the enantiomers of a model chiral probe on disposable screen-printed electrodes in terms of peak potential differences, which is the most desirable transduction mode of the enantiorecognition event. The probe enantiomer sequence is the same for all selectors, consistent with their sharing the same chiral building block configuration. This proof-of-concept widens the application fields of bile acid derivatives as chiral selectors, while also enriching the still very few CIL families so far explored for applications in chiral electroanalysis

Enantioselective voltammetry on achiral electrodes

An attractive target in electroanalysis is the availability of chiral media affording enantioselection in terms of significant peak potential difference between the antipodes of chiral probes in voltammetry experiments on achiral electrodes. Previous literature attempts pointed to enantioselectivity increasing with the structural order of the chiral medium; on the other hand, outstanding enantioselection performance has been recently observed working on electrode surfaces consisting in "inherently chiral" oligomer films [1-2]. Combining both strategies, we have recently developed two inherently chiral ionic liquids, ICILs, consisting of dialkylated bicollidinium salts, with an atropoisomeric bipyridinium cation featuring at least one octyl chain and bistrifilimide counteranions. They showed high enantioselectivity when tested even as low concentration additives in commercial achiral ionic liquid media [3] and also as chiral bulk media. Importantly, similar ability was also shown by other terms of the same family, having shorter alkyl chains and/or different counteranions, solid at room temperature but of easier synthesis. As a first tentative explanation we are considering the high supramolecular order of even simple ionic liquids at the interphase with a charged surface. A chiral additive could result in chiral reorganization of this peculiar interphase, as in the case of nematic-to-cholesteric transitions induced by chiral dopants in liquid crystals. This allowed us to include in our chiral voltammetry experiments a quite larger number of inherently chiral selectors based on different stereogenic elements, i.e., the bicollidine and bibenzimidazole atropoisomeric scaffolds and the tetrathielicene helicoidal scaffold. They all proved successful. The support of Fondazione Cariplo/Regione Lombardia "Avviso congiunto per l\u2019incremento dell\u2019attrattivit\ue0 del sistema di ricerca lombardo e della competitivit\ue0 dei ricercatori candidati su strumenti ERC - edizione 2016\u201d (Project 2016-0923) is gratefully acknowledged. [1] F. Sannicol\uf2, S. Arnaboldi, T. Benincori, V. Bonometti, R. Cirilli, L. Dunsch, W. Kutner, G. Longhi, P. R. Mussini, M. Panigati, M. Pierini, S. Rizzo, Angew. Chem. Int. Ed. 53 (2014) 2623 [2] S. Arnaboldi, P. Mussini, M. Magni, F. Sannicol\uf2, T. Benincori, R. Cirilli, K. Noworyta, W. Kutner, Chem. Sci. 6 (2015) 1706 [3] S. Rizzo, S. Arnaboldi, V. Mihali, R. Cirilli, A. Forni, A. Gennaro, A. A. Isse, M. Pierini, P. R. Mussini, F. Sannicol\uf2, Angew. Chem. Int. Ed 56 (2017) 207

Artificial enantiopure inherently chiral membranes: enantiodiscrimination trough a new “ion-selective like” setup

High-efficiency resolution technology is fundamental for scaling-up separation of enantiomerically pure substances. Membrane technology fulfils this requisite, in fact it is characterized by i) high efficiency, ii) simplicity and iii) convenience for up- and/or down-scaling. Membrane-based chiral resolution can be achieved using either enantioselective or non-enantioselective membranes. Enantioselective membranes can be used for chiral separation of enantiomers because they contain chiral recognition sites. In this frame we have discovered that the electrooligomerization, in acetonitrile as solvent, for 108 deposition cycles, on an ITO electrode support, of our \u201cinherently chiral\u201d benchmark monomer, leads to self-standing racemic or enantiopure membranes. These ones were obtained by simply peeling off the solid deposit from the ITO immersed in water after the electrodeposition in acetonitrile. We have then characterized inherently chiral membranes by a multivariate technique approach (e.g. electrochemical impedance spectroscopy, scanning electron microscopy, BET for surface area and pore size distribution, and atomic force microscopy) comparing the racemic vs enantiopure deposit properties. Considering i) the outstanding enantioselection ability achieved with our both inherently chiral electrode surfaces and media [1-2] and ii) the perfectly specular CD spectra displayed by the two membrane enantiomers, we have decided to implement enantiopure inherently chiral membranes in a \u201cion-selective like\u201d set-up in order to study their enantiorecognition capability (as depicted in Figure on the right). First of all we have verified the potential difference was read correctly through the membrane to allow correct determinations of transmembrane potentials. After that we have tested enantiopure membranes in the presence of chiral charged species (in all configurations for both membranes and internal/external electrode solutions) for determining their enantioselective capability. Preliminary results are very promising and encourage us to perform the scaling up of the membrane electrosynthesis to be used for industrial scopes and to extend the study to other probe useful in the analytical and pharmaceutical field. References: [1] S. Arnaboldi, M. Magni, P. R. Mussini, Curr. Op. in Electrochemistry 8 (2018) 60-72. [2] S. Arnaboldi, S. Grecchi, M. Magni, P.R. Mussini, Curr. Op. in Electrochemistry 7 (2018) 188-199