Separation and characterization of products resulting from the reaction of cis-diamminedichloroplatinum (II) with deoxyribonucleosides

Abstract

The cancer chemotherapeutic drug cis-diamminedichloroplatinum (II) (cis-DDP) was reacted with deoxyribonucleosides, and the products were separated by high-pressure liquid chromatography and characterized by 1H nuclear magnetic resonance. Monofunctional platination occurred at N(3) of cytidine, N(7) of guanosine, N(1) of adenosine, and N(7) of adenosine. Bifunctional platination occurred with guanosine N(7) to N(7), adenosine N(7) to N(7), and adenosine N(1) to N(7). In addition, mixed bifunctional products N(7) of guanosine-N(1) of adenosine and N(7) of guanosine-N(7) of adenosine were obtained. No bifunctional adducts were obtained that contained cytidine, presumably due to steric hindrance as trans-DDP did cross-link two cytidine residues. Similarly, no adenosine N(1) to N(1) was detected with cis-DDP. The only other products detected were obtained at high levels of cis-DDP and probably represented polymeric forms in which platinum chelates to itself.