Quantum molecular simulation of the radioprotection by the aminothiol WR-1065, active metabolite of amifostine (WR-2721) 1. Modeling the [rad]OH scavenging process

Abstract

The modeling of the scavenging mechanism of the free radical OH by the radioprotector WR-1065 in bicationic form was conducted using ab initio computations at the 3-21G ∗ and 6-31G ∗ levels. Quantum properties (frontier orbitals and molecular electrostatic potential) of WR-1065 (in neutral and bicationic forms) and of OH are discussed. The HOMO concentration on the sulfhydryl group of bicationic WR-1065 indicates that this site is the nucleophilic part of the radioprotector which reacts with the electrophilic site (the oxygen atom) of the free radical OH. The simulation of the OH scavenging was conducted using the supermolecule (WR-1065 bicationic+ OH) and the quantum properties of the obtained free radicals were illustrated with the total spin density representation.