The hydrolysis chemistry of anticancer drug titanocene dichloride: An insight from theoretical study

This work reports an investigation of the hydrolysis of anticancer drug titanocene dichloride with the combined density functional theory and continuum dielectric model approach. The hydrolysis of titanocene dichloride includes three typical reactions, i.e., the first, second and third hydrolysis processes, which has been believed a key step before the titanocene complexes interaction with the target biomolecules. The detail knowledge of mechanism of the hydrolysis for titanocene dichloride is a prerequisite for clinical tests and for a successful application for permission as medication. With the analysis of thermodynamics and kinetics, the conclusions predict the activation energies (14-19 kcal/mol) and reaction free energies (0-13 kcal/mol) in aqueous solution for the three hydrolysis reactions, the predicted activation energy and reaction free energy for the second hydrolysis agree well with the available experimental data (the first hydrolysis is too rapid to measure with the experimental methods and the experimental values of thermodynamics and kinetics of the third hydrolysis reaction have not yet been occurred). We also discuss the variations of structural parameters of the three reactions in detail below. The results could contribute to the identification of the active compounds (titanocene dichloride or titanocene analogous) that interact with biological targets.