Atropisomerism of diflunisal unveiled by rotational spectroscopy and quantum chemical calculations

Abstract

Producción CientíficaThe most stable conformer of laser-ablated diflunisal has been isolated in a supersonic expansion and experimentally detected through high-resolution chirped-pulse rotational spectroscopy. State-of-the-art chemical calculations allowed to understand the nature of the strong stabilization of the detected conformer and its atropisomer among a total of sixteen theoretically predicted conformers and confirmed the presence of a resonance assisted hydrogen bond (RAHB) between the hydroxyl hydrogen atom and the carbonyl oxygen atom of the carboxylic acid group. The comparison of the experimental data from this work and the information found in the literature about the molecule in condensed phases corroborates the existence of these two atropisomers and is contextualized within the complexation arrangement of diflunisal with relevant proteins.This project has been funded by grants PID2022-136919NA-C33 of the Ministry of Science, Innovation and Universities MCIN/AEI/10.13039/501100011033. The authors also acknowledge the Ministerio de Ciencia e Innovación (PID2021-125207NB-C33) and the Junta de Castilla y León (Grant INFRARED-FEDER IR2020-1-UVa02). A.V. would like to thank the University of Valladolid and Banco Santander for his Ph.D. grant