Insights into the mechanism of action of platinum anticancer drugs from multinuclear NMR spectroscopy

The kinetics and mechanism of DNA platinization reactions with the detection of platinization sites on proteins and studies of new platinum drugs under investigation are discussed. Both Pt(II) and Pt(IV) are diamagnetic and so their complexes give relatively sharp NMR peak. Pt NMR resonances with their very wide range of chemical shifts can usually be observed from solutions with millimolar concentrations of complexes. In order to gain an understanding of the chemical reactivity of the cis-(PtCl2(NH3)(2-pic)), its crystal structure and hydrolysis behavior have been investigated. Analysis of the rate constants for the stepwise formation of the intrastrand cross-links shows that the aquation of cisplatin is slowed by 30-40% in the presence of the DNA. Platinum anticancer drugs are now widely used in the clinic for the treatment of cancer and much effort is currently directed at designing new platinum drugs which offer a wider spectrum of activity.