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

Strategies for High Enantioselectivity in Electroanalysis: Implementing Inherently Chiral Selectors as Electrode Surfaces or at Electrode|Ionic Liquid Interfaces

Strategies for High Enantioselectivity in Electroanalysis: Implementing Inherently Chiral Selectors as Electrode Surfaces or at Electrode|Ionic Liquid Interfaces Patrizia R. Mussini,*1 Serena Arnaboldi1, Mirko Magni1, Sara Grecchi1, Tiziana Benincori2, Simona Rizzo3, Emanuela Licandro1, Silvia Cauteruccio1, Francesco Sannicol\uf21 1Universit\ue0 degli Studi di Milano, Dip. di Chimica, Via Golgi 19, 20133 Milano, Italy, 2 Universit\ue0 degli Studi dell'Insubria, Dip. di Scienza e Alta Tecnologia, Como, Italy 3 Istituto di Scienze e Tecnologie Molecolari, CNR, Milano, Italy E-mail: [email protected] 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. A groundbreaking strategy was recently proposed, based on the use of "inherently chiral" molecular selectors, i.e. with chirality and key functional properties originating from the same structural element. 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 with atropisomeric or helical scaffolds; (b) working on achiral electrodes, implementing inherent chirality in their interphase with an ionic liquid medium2 exploiting the latter's peculiarly high order. Inherently chiral ionic liquids ICILs were developed as double salts of an atropisomeric 3,3\u2032-bipyridine scaffold with long alkyl chains and a suitable anion, Even more convenient, the new ICILs as well as other family terms solid at room temperature but of easier synthesis, or other inherently chiral salts, can be efficiently applied as low-concentration chiral additives in commercial achiral ionic liquids: large peak potential differences, regularly increasing with additive concentration, have been observed for the enantiomers of different probes on achiral electrodes. Work is in progress to strengthen and rationalize the first proofs of concepts by developing, characterizing and testing a wider variety of inherently chiral selectors with different chiral probes, particularly of pharmaceutical interest, with more optimized and detailed protocols, and with the support of other techniques, particularly aiming to the recognition mechanism elucidation.. 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 Angew. Chem., 2014, 53, 2623. Chem. Eur J. 2014, 20, 15298; Chem. Sci. 2015, 6, 1706; Anal. Bional. Chem. 2016, 408, 7243; Chem. Eur J. 2016, 22, 10839 2 Angew. Chem. 2017, 56, 2079; Electrochem. Comm. 2018, 89, 57

Electrochemistry of inherently chiral molecular materials with bisindole atropisomeric cores: interacting equivalent redox sites, configurational stability, and enantioselection ability for different chiral probes

In "inherently chiral" molecules chirality and key functional properties originate from the same structural element, and are thus strictly linked together. In the case of poly(hetero)aromatic electroactive molecules, this can be achieved by inserting in the main conjugated backbone a tailored torsion with an energy barrier too high to be overcome at room temperature, while not entirely hampering conjugation. This strategy results in outstanding chirality manifestations. including e.g. circularly polarized luminescence as well as outstanding enantiorecognition ability in CV experiments. For instance, large peak potential differences were observed for the enantiomers of different chiral probes on electroactive surfaces obtained by electrooligomerization of inherently chiral monomers having atropisomeric (= with hindered rotation between two moieties) bibenzothiophene (Fig 1A) or bithiophene cores. [1-4]. An interesting option is also to change the thiophene-based atropisomeric cores with 2,2'-bisindole and 3,3'-bisindole ones (Fig 1B and 1C), on account of the easy functionalization of the core e.g. with long alkyl chains, modulating solubility and processability. A B C Figure 1 R = H or C1-C6 alkyl chains; Spacer = phenyl or nothing (oligothiophene wing attached to core) The change also leads to quite interesting modifications in the electrochemical activity. Since indole is electron richer than thiophene, the first two oxidations take place at significantly less positive potentials than in the former cases, and are localized on the two interacting moieties of the bisindole core rather than on the terminal wings; thus, they are chemically reversible (oligomerization can be achieved cycling around the third oxidation peak). A peculiar attractive feature concerns the interaction between the two equivalent redox centers in the biindole core, which can be evaluated from the potential difference between the corresponding oxidation peak: it can be shown that it can account for the atropisomeric energy barrier (depending on the 2,2' or 3,3' connectivity and on the N-alkyl substituents), and is also modulated by temperature and the solvent polarity. Thus electrochemistry can provide information on the torsional energy barrier and on the enantiomer stability, as confirmed by other approaches. Besides the intrinsic interest of these inherently chiral families, they are also quite attractive from the applicative point of view, since enantioselectivity test on films obtained by electrooligomerization of the more stable 2,2' monomers yield large potential differences for the antipodes of very different chiral probes, also of pharmaceutical interest. The current 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) to our inherently chiral research is gratefully acknowledged. References: 1. Angew. Chem. Int. Ed. 2014, 53, 2623. 2. Chem. Eur. J. 2014, 20, 15298. 3. Chem. Sci. 2015, 6,1706. 4. Chem. Eur.2016 , 22,10839. 5. Anal. Bioanal. Chem. 2016, 408, 7243

Triarilfosfine chirali a simmetria C3 come leganti di metalli per la preparazione di catalizzatori per reazioni stereoselettive

The invention refers to the synthesis of some chiral C3 symmetric tris-arylphosphines, tris-heteroarylphosphines in particular, characterized by three identical aryl rings, and to their use as ligands of transition metals for preparing complexes to be emplpyed as homogeneous catalysts in stereoselective reactions. The stereogenic element responsible for enantiofacial recognition is considered to be the helix typical of these three-bladed propellers. A specific helical configuration can be induced either by supplementary stereochemically defined homotopic stereogenic elements present on the aromatic rings or by the correlated rotation of the rings around the carbon-phosphorus bond

Process-scale total synthesis of natural (-)-(S,S)-7-hydroxy-calamenal in high enantiomeric purity through a catalytic enantioselective hydrogenation process

A process-scale stereoselective synthesis of natural (-)-(S,S)-7-hydroxy-calamenal1 in a 96% enantiomeric purity is described. The key step is the enantioselective hydrogenation of easily accessible 2-(4-methoxyphenyl)-3-methyl-2-butenoic acid to (+)-(S)-2-(4-methoxyphenyl)-3-methylbutanoic acid. Enantiomeric excesses up to 86% were achieved with a ruthenium complex of (-)-(R)-TetraMe-BITIOP, a chiral biheteroaromatic diphosphine which was projected by us a few years ago.2 Substantial increase in optical purity up to 96% was achieved by crystallization of intermediate 4-i-propyl-7-methoxy-3,4-dihydro-2H-naphthalene-1-one by seeding the n-hexane solution of the latter with crystals of the enantiopure compound. Computational conformational analysis carried out on (-)-(S)-1-i-propyl-6-methoxy-4-methyl-1,2-dihydronaphthalene explains the high diastereoselection levels attained in the catalytic hydrogenation of the double bond to give (-)-(S,S)-1-isopropyl-6-methoxy-4-methyl-1,2,3,4-dihydro-naphthalene

Artificial Inherently Chiral Electroactive Membranes

Low-cost, continuous, high-efficiency resolution technology is clearly needed for commercial-scale preparation of enantiomerically pure substances. Membrane technology, fortunately, fulfils this need very well because of its high efficiency, low energy usage, simplicity, convenience for up- and/or down-scaling, and continuous operability. Membrane-based chiral resolution can be achieved using either enantioselective or non-enantioselective membranes. The enantioselective membranes themselves can carry out chiral separation of enantiomers because they contain chiral recognition sites [1]. Considering the outstanding enantioselection ability achieved with our inherently chiral surfaces [2] we have decided to synthesize by electrooligomerization inherently chiral membranes. These membranes were electrodeposited on FTO electrodes from the enanantiopure monomers of our inherently chiral forefather (BT2T4) dissolved in acetonitrile + tetrabutylammonium hexafluorophosphate 0.1 M as supporting electrolyte. The chiral membrane detachment is then obtained by dipping the FTO in deionized water. Preliminary tests have shown that they are electroactive with a perfectly specular CD spectra. We have also performed experiments by inserting the enantiopure membrane in a support normally used for ISE electrodes. 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

Transparent electrodes based on silver nanowire networks: from fundamental aspects to integration into device

The past few years have seen a considerable amount of research devoted to nanostructured transparent conducting materials which play a pivotal role in many modern devices such as: solar cells, flexible light-emitting devices, touch screens and flexible transparent thin film heaters. Metallic nanowire networks have recently been a heavily researched subject. Currently, the most commonly used material for such applications is Tin-doped Indium oxide (ITO). Although ITO exhibits very good physical properties, indium scarcity and brittleness have prompted the search for alternative materials. Among emerging transparent electrodes, silver nanowire (AgNW) networks appear as a promising substitute to ITO since these percolating networks exhibit excellent properties with sheet resistance of a few Ω/sq and optical transparency of 90%, fulfilling the requirements for many applications. It also shows very good electro-mechanical properties. In addition, the fabrication of these electrodes involves low-temperature process steps and upscaling methods, thus making them very appropriate for future use as TE for flexible devices. Our research is focused on the fundamental understanding of the physical phenomena taking place at the scales of both the network (macroscale) and the NW-to-NW junctions (nanoscale), and on the ability of AgNW networks to be integrated as transparent electrodes for different applications. In-situ electrical measurements performed during optimisation process such as thermal annealing provide useful information regarding the activation process of the junctions. This contribution aims at presenting a short overview of the main properties and applications of metallic nanowire networks, as well as the integration in devices