Short-lived intermediates (encounter complexes) in cisplatin ligand exchange elucidated by infrared ion spectroscopy

Cisplatin (cis-diamminedichloroplatinum(II), cis-[PtCl2(NH3)2]), widely used drug in cancer treatment, has been allowed to react with simple molecular targets (L) mimicking biological functional groups. The selected molecules (L = acetamide, dimethylacetamide, urea and thiourea) react by ligand exchange leading to cis-[PtCl(NH3)2(L)]+ complexes that have been assayed by ESI-MS, IRMPD spectroscopy and computations in order to characterize their structure and platination site. Formal five-coordinate complexes are also delivered by ESI, [(PtCl(NH3)2(H2O)(L)]+, notably absent only when L is thiourea. IRMPD spectroscopy combined with computational analysis has revealed non-covalent adducts of the reactant aqua complex with an external ligand L corresponding to {cis-[PtCl(NH3)2(H2O)]+ · L}, reminiscent of the Eigen-Wilkins encounter complex invoked in the ligand displacement path in solution. The complex, successfully isolated in the gas phase, undergoes ligand exchange yielding cis-[PtCl(NH3)2(L)]+ + H2O when activated by multiple IR photons, testifying at the same time both structure and reactivity.