Quantum molecular simulation of the radioprotection by the aminothiol WR-1065, active metabolite of amifostine (WR-2721).: Part 2.: Modeling of the hydrogen abstraction by C4′ of DNA deoxyribose radical

The modeling of the mechanism of hydrogen donation at C4' deoxyribose radical by the radioprotector WR-1065 in bicationic form, was conducted using a supermolecular model [(Na(+)p d C(.)pNa(+)) + WR-1065] and ZINDO 1 and ab initio computation. The mechanism of the hydrogen reparation of the sugar-radical by the aminothiol is discussed with regard to the location of frontier orbitals and total spin density onto the reactants. The quantum properties of the obtained WR-1065 in thiyl radical form (with S) and of the symmetrical disulfide WR-33278 are presented and discussed. (C) 2001 Elsevier Science B.V. All rights reserved.