Chemical Repair of Damaged Leucine and Tryptophane by Thiophenols at Close to Diffusion-controlled Rates: Mechanisms and Kinetics

Thiophenols are chemical species with multiple desirable biological properties, including their primary and secondary antioxidant capacity. In this work, the repairing antioxidant activity of eight different thiophenols has been investigated for damaged leucine and tryptophane. The investigation was carried out employing quantum mechanical and transition state methods to calculate the thermodynamic and kinetic data of the reactions involved, while simulating the biological conditions at physiological pH and aqueous and lipidic medium. The analysis of the atomic charges and the spin densities at each of the points on the potential energy surface was the tool that allowed the elucidation of the reaction mechanisms through which thiophenols repair the oxidative damage caused to the amino acids leucine and tryptophan. It was found that thiophenols can repair leucine via a hydrogen atom transfer mechanism in a manner which is similar to the one used by glutathione to repair the carbon-centered radicals of guanosine. In addition, thiophenols can also restore tryptophane, a nitrogen-centered radical, via proton-coupled electron transfer and single electron transfer mechanisms. Moreover, both processes occur at close to diffusion-controlled rates.