Reaction of HSSS. radical with guanine and formation of 8-thioguanine: a computational study

Density functional calculations have been applied to study reactions of the HSSS. radical with guanine at the C2, C4, C5, and C8 sites of guanine that yields [GCn-SSSH].n = 2, 4, 5, and 8 adducts. Also, formation of 8-thioguanine from [GC8-SSSH]. adduct has been studied. In all the adducts [GCn-SSSH]., HSSS. radical is placed on the top of the plane of the guanine ring. The results show that there is a possibility of intraresidue S-H…N hydrogen bonding in each [GCn-SSSH]. adduct. Besides, the C8 site of guanine is the most reactive site to add to HSSS. radical with appreciably high rate constant, and the adduct formed at this site would be significantly stable. According to NBO analysis, delocalization energies for all the hydrogen bondings, i.e., E(2) for nN⟶σ*SH interactions, are obtained to be in the range of 1.31–3.46 kcalmo1−1. The biggest E(2) and the largest amount of charge transfer is found for [GC8-SSSH]. adduct, i.e., for the S-H…N7 (Gua) interaction, in which RN…H = 2.588 Å, to be 1.78 kcalmo1−1 and 0.0024e, respectively, well correlated with the prediction of most of its stability among the [GCn-SSSH]. adducts. The ZPE-corrected enthalpy changes for the reactions are obtained to be 0.2–1.4 kcalmo1−1. The reaction enthalpy changes and the barrier energies related to the different sites of guanine are found to be in the order of C8 < C2 < C5 < C4. Starting with the adduct [GC8-SSSH]., 8-thioguanine could be achieved in two steps with two transition states (TS1 and TS2) and an intermediate complex (IM); the overall reaction is exothermic. The first reaction step, the rate-determining step, involves going from the adduct [GC8-SSSH]. to IM via TS1, in which HSS moiety gets dissociated from the HSSS moiety attached to the C8 site of guanine