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 sy nthesized, 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 simult aneously formed, II in larger proportion than III. These products were isol ated after HPLC purification and extensively characterized. Both II and III contained platinum, had the same mass and showed a bathochromic displaceme nt of their absorption maxima with respect to that of I. Both remained unde graded upon enzymatic digestion and yielded I when treated with NaCN. From these data and the information provided by H-1 NMR analysis, we inferred th at 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 eithe r of these N-donors was observed.