A CNDO/2 study on bonding mechanism of cis-dichlorodiammine platinum (II) with DNA

Bonding mechanism of cis-Pt(NH_3)_2Cl_2 with DNA has been studied by CNDO/2 cal- culation.The computed results of the six models considered indicated that from the point of view of overlap population Q)(AB)and two atoms energy E_(AB),the most favorable bonding form was that between platinum and two N_7 atoms,from guanines(G)to form [(NH_3)_2PtG_2]~(2+).Thus,intrastrand cross-linkage mechanism which had been previously proposed by some authors was confirmed by our calculation.Chelation mechanism could not completely be excluded.Under certain conditions, it was possible for platinum to combine with a guanine through its N_7 and O(C_6)to form a chelate, but it was unstable as compared with [(NH_3)_2PtG_3]~(2+). Although the intrastrand cross-linkage mechanism is favored by our calculation,the question of how such a mode of combination hampers replication of DNA remains to be solved.