H/D Exchange Processes in Flavonoids: Kinetics and Mechanistic Investigations

Federico Bonaldo; Fulvio Mattivi; Daniele Catorci; Panagiotis Arapitsas; Graziano Guella

doi:10.3390/molecules26123544

H/D Exchange Processes in Flavonoids: Kinetics and Mechanistic Investigations

Molecules. 2021 Jun 10;26(12):3544. doi: 10.3390/molecules26123544.

Authors

Federico Bonaldo¹, Fulvio Mattivi², Daniele Catorci¹, Panagiotis Arapitsas³, Graziano Guella¹

Affiliations

¹ Bioorganic Chemistry Laboratory, Department of Physics, University of Trento, 38123 Trento, Italy.
² Department of Cellular, Computational and Integrative Biology-CIBIO and C3A, University of Trento, 38123 Povo Trento, Italy.
³ Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), 38098 San Michele all'Adige, Italy.

Abstract

Several classes of flavonoids, such as anthocyanins, flavonols, flavanols, and flavones, undergo a slow H/D exchange on aromatic ring A, leading to full deuteration at positions C(6) and C(8). Within the flavanol class, H-C(6) and H-C(8) of catechin and epicatechin are slowly exchanged in D₂O to the corresponding deuterated analogues. Even quercetin, a relevant flavonol representative, shows the same behaviour in a D₂O/DMSOd₆ 1:1 solution. Detailed kinetic measurements of these H/D exchange processes are here reported by exploiting the time-dependent changes of their peak areas in the ¹H-NMR spectra taken at different temperatures. A unifying reaction mechanism is also proposed based on our detailed kinetic observations, even taking into account pH and solvent effects. Molecular modelling and QM calculations were also carried out to shed more light on several molecular details of the proposed mechanism.

Keywords: H/D isotopic exchange; NMR spectroscopy; flavonoids; kinetics; reaction mechanism.