Dimerization of quercetin, Diels-Alder vs. radical-coupling approach: a joint thermodynamics, kinetics, and topological study

  • Isabelle Fourré
  • Florent Di Meo
  • Pavlína Podloucká
  • Michal Otyepka
  • Patrick Trouillas
Original Paper

Abstract

Quercetin is a prototypical antioxidant and prominent member of flavonoids, a large group of natural polyphenols. The oxidation of quercetin may lead to its dimerization, which is a paradigm of the more general polyphenol oligomerization. There exist two opposing mechanisms to describe the dimerization process, namely radical-coupling or Diels-Alder reactions. This work presents a comprehensive rationalization of this dimerization process, acquired from density functional theory (DFT) calculations. It is found that the two-step radical-coupling pathway is thermodynamically and kinetically preferred over the Diels-Alder reaction. This is in agreement with the experimental results showing the formation of only one isomer, whereas the Diels-Alder mechanism would yield two isomers. The evolution in bonding, occurring during these two processes, is investigated using the atoms in molecules (AIM) and electron localization function (ELF) topological approaches. It is shown that some electron density is accumulated between the fragments in the transition state of the radical-coupling reaction, but not in the transition state of the Diels-Alder process.

Graphical Abstract

Quantum chemistry calculations of the dimerization process of quercetin show that a radical coupling approach is preferred to a Diels-Alder type reaction, in agreement with experimental results. Analysis of the bonding evolution highlights the reaction mechanism.

Keywords

Antioxidants Atoms in molecules (AIM) Density functional theory Electron localization function (ELF) Flavonoids Kinetics Thermochemistry 

Supplementary material

894_2016_3051_MOESM1_ESM.doc (706 kb)
ESM 1Electronic supplementary information (ESI) available: additional ELF parameters (Tables S1, S2, S3), M06-2X/6-31+G(d,p)//M06-2X/6-31G(d) Gibbs energies of all reaction steps and of activation barriers for both Diels-Alder and radical-coupling reactions (Table S4), 3D structures of the intermediate state (radical coupling approach), and of the dimers (Fig. S1), 3D structure of the transition state of the Diels-Alder type reaction (Fig. S2), potential energy curves for the intermediate dimer formation in the radical coupling approach (Figs. S3) (DOC 705 kb)

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© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Sorbonne Universités, UPMC Univ Paris 6CNRS, Laboratoire de chimie théoriqueParisFrance
  2. 2.Inserm U850Univ Limoges, Faculty of PharmacyLimogesFrance
  3. 3.Department of Physics, Chemistry and Biology (IFM)Linköping UniversityLinköpingSweden
  4. 4.Regional Centre for Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of SciencePalacký UniversityOlomoucCzech Republic

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