Study of the interaction between a histidine-deoxyguanosine hybrid and cisplatin

A histidine-2'-deoxyguanosine hybrid, Phac-Hse(p(5') dG)-His-OH (I), was synthesized, and its reaction with cisplatin was monitored by reversed-phase HPLC and H-1 NMR. Two new compounds, II and III, were observed to be simultaneously formed, II in larger proportion than III. These products were isolated after HPLC purification and extensively characterized. Both II and III contained platinum, had the same mass and showed a bathochromic displacement of their absorption maxima with respect to that of I. Both remained undegraded upon enzymatic digestion and yielded I when treated with NaCN. From these data and the information provided by H-1 NMR analysis, we inferred that II and III were constitutional isomers, in particular chelates in which platinum was coordinated to the N7 of guanine and either the N-pi or the N-tau imidazole nitrogens, respectively. No preference of the metal for either of these N-donors was observed.