Activation and Reactivity of a Bispidine Analogue of Cisplatin: A Theoretical Investigation

The reactivity of a bispidine, 3,7-diazabicyclo[3.3.1]nonane, analogue of cisplatin, a new anticancer drug with promising properties, is theoretically investigated to clarify the in vitro reactivity and in vivo mechanism of action of this compound. Thermodynamics and kinetics of the first and second aquation steps and of the reaction of the generated mono- and diaqua species with guanine, the main target of the platinum based antitumor compounds, have been studied. In agreement with the experimental evidence, the bispidine analogue is significantly less reactive than cisplatin toward aquation but the formed aquaspecies show a good reactivity with guanine, consistently with the promising anticancer properties of these new compounds.