Aquation of the ruthenium-based anticancer drug NAMI-A: a density functional study.

We carried out density functional theory (DFT) calculations to investigate the thermodynamics and the kinetics of the double aquation reaction of the anticancer drug NAMI-A. Three explicit water molecules were included in the calculations to improve the PB solvation energies. Our calculations show that the chloride substitution reactions on the considered Ru(III) octahedral complex follow a dissociative interchange mechanism, I(d), passing through a loose heptacoordinate transition state. We calculated an activation enthalpy and free energy for the first aquation step of 101.5 and 103.7 kJ mol(-1), respectively, values that are in good agreement with the available experimental results. The activation enthalpy and free energy for the second aquation step were found significantly higher, 118.7 and 125.0 kJ mol(-1), again in agreement with the experimental evidence indicating a slower rate for the second aquation.