We carried out a theoretical study to investigate the thermodynamics and the kinetics of the activation of the anticancer drug carboplatin in a carbonate buffer, a process which has been suggested to play an important role in the uptake, antitumor activity and toxicity of this drug. The initial stages of this process have been investigated by considering both the carbonate and the bicarbonate ions, the main species in a carbonate buffer at physiological pH, as the attacking species and consist of an initial ring-opening step, involving the displacement of one arm of the chelating ring by the carbonate ion, followed by the protonation of the ring-opened carbonate to the corresponding bicarbonate species and its subsequent decarboxylation to give the final hydroxo product. The obtained results show that the overall process is exoergonic with relatively low activation free energy (below 120 kJ mol−1), suggesting that the reaction with carbonate might represent a viable pathway for the activation of carboplatin to give active intermediates which, in the biological environment, may easily further react to give thermodynamically more stable species.
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