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

Electroactive Inherently Chiral Surfaces at Work: Clues Toward the Elucidation of the Enantioselection Mechanism

Chirality is a concept strictly related to life and to its evolution. Capability to discriminate antipodes and/or produce enantiopure chiral chemicals through cheap and efficient protocols is a crucial task for our modern civilization. So identification of increasingly effective and robust chiral selectors is a challenging task also for the electrochemical community [1,2]. In this frame our research group is working on the so called \u201cinherently chiral functional molecular materials\u201d, ICFMMs; the idea is simple: make the stereogenic element responsible for chirality coincident with the functional group responsible for the material specific property (Figure, left). This approach has constituted an actual breakthrough in chiral electrochemistry, resulting in the preparation of efficient chiral electroactive surfaces [3,4,5] (and chiral additives/media, too [6]) invariably characterized by outstanding enantiodiscrimination ability in quite different working conditions and with chemically different chiral electroactive analytes. Notwithstanding plenty of proofs pointing to a general validity of the ICFMMs concept, a clear rationalization of the enantiodiscrimination mechanism still lacks. To fill the gap a deeper knowledge of the behavior of our electrodeposited chiral films is mandatory. As a first step some of the most important experimental parameters governing the growth of the conductive coatings have been changed, one by one, to evaluate their impact on the morphological, optical and electronic properties of the final deposit. Results of the multi-technique characterization will be discussed, including profilometry, electrochemical impedance spectroscopy (Figure, right) and spectroelectrochemistry data, all aimed to collect clues useful to rationalize the way in which ICFMMs work. The support of Fondazione Cariplo/Regione Lombardia (Project 2016-0923) and SmartMatLab are gratefully acknowledged. References: [1] S. Arnaboldi, M. Magni, P. Mussini, Curr. Opin. Electrochem., 2018, 8, 60. [2] S. Arnaboldi, S. Grecchi, M. Magni, P. Mussini, Curr. Opin. Electrochem., 2018, 7, 188. [3] F. Sannicol\uf2, P.R. Mussini, T. Benincori, R. Martinazzo, S. Arnaboldi, G. Appoloni, M. Panigati, E. Quartapelle Procopio, V. Marino, R. Cirilli, S. Casolo, W. Kutner, K. Noworyta, A. Pietrzyk-Le, Z. Iskierko, K. Bartold, Chem. Eur. J., 2016, 22, 10839. [4] S. Arnaboldi, P.R. Mussini, M. Magni, F. Sannicol\uf2, T. Benincori, R. Cirilli, K. Noworyta, W. Kutner, Chem. Sci., 2015, 6, 1706. [5] 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., 2014, 53, 2623. [6] 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., 2017, 56, 2079

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

Panoramic Overview on the Enantioselection Performance of Inherently Chiral Surfaces: a Comparison between Systems with Different Atropisomeric Cores and Stereogenic Elements

Enantiorecognition is a key issue in advanced analytical chemistry, particularly concerning the biological and pharmaceutical field. Enantiomeric molecules, being mirror-image structures, have identical physico-chemical scalar properties, but opposite pseudo-scalar ones. When interacting with a racemic probe, chiral molecules are able to recognize the enantiomers through diasteromeric interactions. Similarly, chiral electrodes are required for enantioselective electroanalysis, and the development of "intelligent" electrodes capable of discriminating enantiomers, in particular molecules of biological and pharmaceutical importance, remains as one of the major challenges in electroanalysis. We have recently proposed the first synthetic inherently chiral electrode surfaces able to neatly discriminate as separate peaks (in terms of potential values) the antipodes of model chiral probes, also drugs, both as enantiopure and racemate. [1-2] We have also verified the general validity of the inherently chiral concept, which does not depend from the chemical nature of the atropisomeric scaffold, testing chiral surfaces electrooligomerized from starting monomers with different molecular design (i.e. bithiophene, bibenzothiophene, biindole and paracyclophane cores) and different stereogenic elements (stereogenic axis vs helix vs plane). In order to fully elucidate the enantioselection capability of all of these heteroaromatic systems we propose a detailed comparison (an example in Figure) of our inherently chiral surfaces with different atropisomeric core vs thiahelicene-based films vs \u201ctwo floor\u201d paracyclophanic oligomers. Figure. Enantioselection properties of inherently chiral oligomers with bibenzothiophene and biindole units towards L- and D-DOPA probes. 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. References: [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) 2623-2627. [2] S. Arnaboldi, T. Benincori, R. Cirilli, W. Kutner, M. Magni, P. R. Mussini, K. Noworyta, F. Sannicol\uf2, Chem. Sci., 6 (2015) 1706-171

Inherently chiral, highly electroactive macrocyclic oligothiophenes: a new class with a "Portfolio" of outstanding potentialities

We have recently introduced1,2,3 an entirely new class of chiral oligothiophene macrocycles, easily accessible by either chemical or electrochemical oxidation of monomers, like the BT2-T4 one in Figure 1 (taken from ref. 3), endowed with "inherent chirality". Such property stems from a tailored torsion in the main conducting backbone,1,2 corresponding to a high rotational energy barrier. Thus the monomer can be separated into stable enantiopure antipodes, whose chirality is entirely transferred to the corresponding cyclic oligomers. The new molecules possess an uncommon pool of outstanding properties even as racemates. For example: \ub7 they idealize conducting polymers without end, that is, without defectivity connected with free terminals; \ub7 in CV and EIS experiments they exhibit very fast and reversible electron transfer and charge transport; \ub7 their HOMO and LUMO levels, which are modulable with the multiplicity and length of the monomer units in the cyclic oligomer, appear convenient for application in devices like bulk heterojunction solar cells; \ub7 they are electrochromic; \ub7 they exhibit (negative) photocurrent activity. Most impressive, however, are the properties as enantiopure antipodes, possibly as a consequence of the unique coincidence of the source of both chirality and electroactivity with the entire main conducting backbone, which affords inter alia to reversibly modulate chiroptical properties by electrochemical polarization. The enantiopure oligomers exhibit: \ub7 impressive optical rotatory power; \ub7 impressive circular dichroism signals, which can be finely and reversibly modulated by the electrical potential ("breathing chirality"); \ub7 remarkable circularly polarized luminescence (CPL); \ub7 outstanding enantiorecognition ability. In particular, we have recently highlighted3 their applicative potentialities as low-cost and easy-to-prepare artificial enantiopure electrode surfaces, which display an unprecedented ability to pronouncedly separate voltammetry peaks of enantiomers of quite different chiral probes, including the model ferrocenyl one in Figure 2 (adapted from ref. 2, and where 3 stays for the BT2-T4 cyclic trimer), or of applicative interest (e.g. pharmaceutical ones like DOPA, Figure 3 from ref. 3), concurrently with linear dynamic ranges for peak currents, affording enantiomer excess determination, particularly on disposable SPEs, testing small drops of enantiomer solutions. It is also remarkable that, while usual chiral recognition methods are based on selectors of natural origin and therefore available as a single enantiomer, this approach offers availability of both selector enantiomers. Thus inherently chiral enantiopure electrodes can indeed be regarded as a key to chiral voltammetry. With the contribution of Fondazione Cariplo, grant no.2011-0417 Patent deposited MI2014A000948-23/05/2014 References: [1] F. Sannicol\uf2, P.R. Mussini, T. Benincori, S. Arnaboldi, M. Panigati, E. Quartapelle Procopio et al., Chem. Eur. J. 2014, 20, 15298 \u2013 15302. [2] F. Sannicol\uf2, S. Arnaboldi, T. Benincori, P.R. Mussini, M. Panigati et al., Angew. Chem. Int. Ed. 2014, 53, 2623 \u20132627. [3] S. Arnaboldi, T. Benincori, R. Cirilli, W. Kutner, M. Magni, P.R. Mussini, K. Noworyta, F. Sannicol\uf2, Chemical Science, 2015, 6, 1706\u20131711

Electrochemistry of Inherently Chiral Thiophene-based Materials in Achiral and Chiral Ionic Liquids

Recently, ionic liquids have been frequently proposed as convenient substitutes for VOCs-supporting electrolyte systems in a variety of electrochemical processes. In particular, recent studies show that they are very good electrodeposition media for inorganic and organic conducting films, on account of their peculiar features. In this frame, our ongoing studies on redox properties and electrooligomerization of inherently chiral thiophene-based molecular materials[1] provide a particularly significant and attractive test for both achiral and chiral ionic liquids as reaction media. 1) Achiral ionic liquids as electrodeposition media for the preparation of inherently chiral electrode surfaces of outstanding reproducibility and enantioselectivity. In our above cited research only a slight discrimination of chiral enantiomeric probes could be observed on films electrodeposited in a traditional 3-electrode minicell from traditional VOCs-supporting electrolyte systems, in spite of an outstanding chiroptical activity of the materials (CD spectroelectrochemistry). This was associated with (a) insufficient reproducibility in the deposited films arising from insufficient reproducibility in the cell geometry and solution concentration, and (b) from insufficient regularity and compactness of the deposited films. The problem was completely solved turning to screen printed supports in combination with an ionic liquid medium (BMIM+ PF6 \uf02d), granting the desired reproducibility together with the possibility to perform the electrodeposition from a small drop (20 microliter and less) of monomer solution, resulting in electrodeposited electrode surfaces of outstanding reproducibility, stability and enantiorecognition performances. 2) Electrochemical tests on chiral monomers and electrodeposited oligomer films in chiral ionic liquid (CILs). A step further consists in evaluating the reactivity of our chiral monomers and electrodeposited oligomer films, both as racemic and enantiopure, in chiral ionic liquids, both racemic and enantiopure, focusing on reciprocal recognition manifestations, applying electrochemical techniques such as CV, EIS and EQCM. For this aim we are considering both commercially available CILs and a new series of CILs currently under development in our laboratories, based on the same innovative inherent chirality approach as the oligomers to be tested. With the contribution of Fondazione Cariplo, grant no. 2011-1851. [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

The thiophene-based inherently chiral monomer family grows: molecular design and electrochemical properties

Our group has recently presented electroactive thiophenebased polyconjugated films of unprecedented chirality manifestations and enantiorecognition ability,[1] based on the "inherent chirality" concept, implying that the whole electroactive backbone coincides with the stereogenic element, consisting in a tailored torsion induced by an atropisomeric bi-benzothiophene scaffold. Such films are easily prepared as enantiopure electrode surfaces by electrooligomerization of (R) and (S) enantiopure monomer 1. Now, concurrently with the exploration of the applicative potentialities of this "parent" molecular material, both racemic and enantiopure, we are widening the class of available monomers designed according the same strategy, but with different atropisomeric heteroaromatic scaffolds, different side chains, and/or with the addition of a further stereogenic element. The electrochemical properties of a selection of the new inherently chiral monomers now available will be presented in detail and rationalized as a function of their molecular structure, also in the perspective of potential applications. With the contribution of Fondazione Cariplo, grant no. 2011-0417. [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. Chemie 2014, 53, 2623-2627