In the present work, the hydrolysis process of non-classical transplatin(II) with two same planar heterocycle amines has been studied using hybrid density functional theory (B3LYP) and IEF-PCM solvation models. Optimizations were performed at the B3LYP level using a combined basis set of (LanL2DZ＋6-31＋G(d,p)) with single-point energy evaluations using the B3LYP/6-31＋＋G(3df,2pd) approach in vacuo and in aqueous solution. For the obtained structures of reactants, intermediates, transition states, and products, both thermodynamic (reaction energies and Gibbs energies) and kinetic (reaction barriers) characteristics were estimated. In comparison with cisplatin, decreased activation energies were obtained. The result implies that the non-classical transplatin with two same planar heterocycle amines increases the equatorial steric effect and lowers reaction barriers, which may assist in designing novel Pt-based anticancer drugs.

Hydrolysis of trans-dichloro(ammine)(quinoline)platinum, a novel potential anticancer drug, is believed to be the key activation step before the drug reaches its intracellular target DNA. To obtain an accurate hydrolysis mechanism for this nonclassical class of square-planar Pt (II) complex, five different models were used at the experimental temperature with the solvent effect B3LYP/PCM using hybrid density functional theory. The stationary points on the potential energy surfaces for the first and second hydrolysis steps, proceeding via a five-coordinate trigonal-bipyramidal (TBP)-like structure of transition state, were fully optimized and characterized. The most remarkable structural variations in the hydrolysis process were found to occur in the equatorial plane of the TBP-like structures of the intermediates and transition states. It was found that the explicit solvent effect originating from the inclusion of extra water molecules into the system is significantly stronger than those arising from the bulk aqueous medium, especially for the first aquation step, which emphasizes the use of appropriate models for these types of problems. The results give detailed energy profiles for the mechanism of hydrolysis of trans-dichloro(ammine)(quinoline)platinum, which may assist in understanding the reaction mechanism of the drug with DNA target and in the design of novel platinum-based anticancer drugs with trans geometries.

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