Designing Powerful Biindole-Based Inherently Chiral Selectors: Enhancing Enantiodiscrimination by Core Functionalization with Additional Coordination Elements

0584857 - ÚFCH JH 2025 RIV DE eng J - Journal Article
Grecchi, S. - Bonetti, G. - Emanuele, E. - Ludvík, Jiří - Koláčná, Lucie - Liška, Alan - Hromadová, Magdaléna - Arnaboldi, S. - Cirilli, R. - Mussini, P. R. - Benincori, T.
Designing Powerful Biindole-Based Inherently Chiral Selectors: Enhancing Enantiodiscrimination by Core Functionalization with Additional Coordination Elements.
Chemistry - A European Journal. Roč. 30, č. 23 (2024), č. článku e202303530. ISSN 0947-6539. E-ISSN 1521-3765
R&D Projects: GA ČR(CZ) GA21-23261S; GA ČR(CZ) GA21-13458S
Research Infrastructure: e-INFRA CZ II - 90254
Institutional support: RVO:61388955
Keywords : electrochemistry * potentials * electrode * naproxen * pharmaceuticals * sensor * Biindole-based inherently chiral selectors * Additional coordination elements enhancing enantiodiscrimination * Chiral electrode surfaces by electrooligomerization * Chiral voltammetry * Enantiodiscrimination in voltammetric analysis of naproxen and ketoprofen NSAIDs
OECD category: Electrochemistry (dry cells, batteries, fuel cells, corrosion metals, electrolysis)
Impact factor: 4.3, year: 2022
Method of publishing: Limited access
https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/chem.202303530

Among inherently chiral selectors of axial stereogenicity, usually resulting in very good enantiodiscrimination performances, the biindole-based family has the additional advantage of very easy functionalization of the two nitrogen atoms with a variety of substituents with desirable properties. Aiming to evaluate the possibility of exploiting such feature to enhance the enantiodiscrimination ability of the archetype structure, a series of three inherently chiral monomers were designed and synthesized, characterised by a 2,2´-biindole atropisomeric core conjugated to bithiophene wings enabling fast and regular electrooligomerization, and functionalised at the nitrogen atoms with an ethyl, a methoxyethyl, or a hydroxyethyl substituent. Nitrogen alkylation was also exploited to obtain for the first time the chemical resolution of the biindole selectors without employing chiral HPLC. The enantiodiscrimination ability of the selector series was comparatively evaluated in proof-of-concept chiral voltammetry experiments with a ´´benchmark´´ chiral ferrocenyl probe as well as with chiral non-steroidal anti-inflammatory drugs naproxen and ketoprofen. The large enantiomer potential differences for all probes increased in the ethyl < methoxyethyl MUCH LESS-THAN hydroxyethyl sequence of selector substituents, supporting our assumption on the beneficial role of an additional coordination element. The powerful hydroxyethyl selector was also applied to ketoprofen in a commercial drug matrix.
Permanent Link: https://hdl.handle.net/11104/0352645