trans-Platinum anticancer drug AMD443: A detailed theoretical study by DFT–TST method on the hydrolysis mechanism

The two-step hydrolysis of trans-[PtCl2(NH3)(2 picoline)], AMD443, a novel anticancer drug has been investigated using density functional theory (DFT) with and without a number of explicit solvent molecules. Pentacoordinated trigonal–bipyramidal (TBP)-like structure transition state (TS) along with other stationary points on potential energy surface were optimized and characterized. To obtain accurate energies for the reaction surfaces, single-point energies were calculated by conductor-like polarisable calculation model (CPCM) using larger basis sets. Significant differences in the geometry and position of the TBP transition state are found between explicitly solvated and gas phase structures. The computed values of rate constant of different steps are in good agreement with the available experimental results.