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

摘要

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 molecualr 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.