Singlet oxygen reactions with flavonoids. A theoretical-experimental study.

Javier Morales,Antonio L Zanocco,Germán Günther,Else Lemp,Nikolai Lebedev

doi:10.1371/journal.pone.0040548

Abstract

Detection of singlet oxygen emission, λmax = 1270 nm, following laser excitation and steady-state methods were employed to measure the total reaction rate constant, kT, and the reactive reaction rate constant, kr, for the reaction between singlet oxygen and several flavonoids. Values of kT determined in deuterated water, ranging from 2.4×107 M−1s−1 to 13.4×107 M−1s−1, for rutin and morin, respectively, and the values measured for kr, ranging from 2.8×105 M−1s−1 to 65.7×105 M−1s−1 for kaempferol and morin, respectively, being epicatechin and catechin chemically unreactive. These results indicate that all the studied flavonoids are good quenchers of singlet oxygen and could be valuable antioxidants in systems under oxidative stress, in particular if a flavonoid-rich diet was previously consumed. Analysis of the dependence of rate constant values with molecular structure in terms of global descriptors and condensed Fukui functions, resulting from electronic structure calculations, supports the formation of a charge transfer exciplex in all studied reactions. The fraction of exciplex giving reaction products evolves through a hydroperoxide and/or an endoperoxide intermediate produced by singlet oxygen attack on the double bond of the ring C of the flavonoid.

Highlights

The association of Reactive Oxygen Species (ROS) to several human physiopathologies has stimulated an increasing interest in studies thereof over the last few decades
The first two types of oxidation consist of a combination of reactions involving triplet oxygen, 3O2, which could be considered as a ground-state biradical OO, and singlet oxygen, O2(1Dg), which corresponds to the first excited state of the molecule
1O2zF kr products where kd is the solvent dependent decay rate constant of singlet oxygen that determines its intrinsic lifetime in a given solvent, kQ is the second-order rate constant of the physical quenching, and kr is the second-order rate constant of the reactive pathway

Summary

Introduction

The association of Reactive Oxygen Species (ROS) to several human physiopathologies has stimulated an increasing interest in studies thereof over the last few decades. For the photosensitized oxidation of flavonoids has been suggested a reaction mechanism involving a hydroperoxide intermediate formed by singlet oxygen attack to the double bond of ring C in a like-ene reaction, or an endoperoxide intermediate produced by [2+2]-cycloaddition of the singlet oxygen to the double bond of the same ring [17,18] These intermediates have been proposed mainly considering the analysis of reaction products and not correlations between theoretical parameters that account for the molecular charge density and empirically obtained kinetic data. We consider several structural requirements in the molecules to be studied that allow us to get a more detailed picture of the flavonoid reactivity towards singlet oxygen These requirements are: (i) the presence of a catechol moiety in the B-ring; (ii) presence or absence of a 2,3-double bond in conjugation with a 4-oxo function in the C-ring; (iii) the substitution of the hydrogen of the hydroxyl group in position 3 of the C-ring by a bulky sugar derivative. Effects on reactivity can be due to the substitution of the hydroxylic hydrogen at position 3 of C-ring, and the possible interaction between the oxygen atom at position 1 of C-ring with the hydroxyl group on position 29 of B-ring

Methods

Results

Conclusion