On the Importance of Water Molecules in the Theoretical Study of Polyphenols Reactivity toward Superoxide Anion

Numerous studies have shown the benefits of a diet rich in fruits and vegetables. These benefits are partly due to the radical scavenging properties of polyphenols contained in fruits and vegetables since polyphenols can fight against an excess of radicals which goes along inflammation in a certain number of diseases. This pathological state, called oxidative stress, results from the aerobic condition of human organism when OH radical, hydrogen peroxide, superoxide anion, or peroxynitrite is produced in excess. If hydrogen peroxide is easily handled by human defense against radicals, the other radicals can cause damage to biological constituents like lipids, cell membranes, and other biomolecules. This paper is devoted to the theoretical study of the interaction of superoxide anion ( ) with a very potent radical scavenger, 1,2,4,6,8-pentahydroxynaphthalene. The importance of hydration of superoxide radical for the reactivity is analyzed. Potential energy surfaces (PES) are calculated for different number of water molecules around the radical and it is shown that the transition barrier vanishes when complete hydration with six water molecules is explicitly handled. The nature of the reactivity is determined by using the natural bond orbital (NBO) analysis. 1. Introduction The production of radicals in the body is a consequence of the aerobic metabolism of the organism [1]. Free radical reactive oxygen species (ROS) can be produced during mitochondrial dysfunction or in pathophysiological conditions. Superoxide anion is one of the most important and biologically relevant ROS radicals in living organisms. It is formed from one-electron reduction of oxygen. It is much less reactive and much more selective than hydroxyl radical which reacts with most biomolecules at a nearly diffusion-controlled rate (1010？M？1s？1). The lifetime of superoxide in biological systems is typically a few seconds. It can react with another superoxide anion to give hydrogen peroxide or with nitric oxide to form a very potent oxidant, peroxynitrite. Superoxide anion is also produced by an enzyme, NADPH, in phagocytes to kill invading pathogens. Although is not a strong microbicidal [1], it is essential for bacterial killing. It is a source of hydrogen peroxide, , which in presence of released iron could form hydroxyl radical via the Fenton mechanism: or the Haber-Weiss mechanism: There are several pathological cases where overproduction of superoxide leads to tissue damage, in particular in ischemic episodes [2]. The deprivation of oxygen, a consequence of severe restriction in blood