Quantum chemical description of the properties and reaction mechanisms of selected anticancer metallodrugs with biomolecules
J.V. Burda
Department of Chemical Physics and Optics
Charles University in Prague
121 16 Prague 2,Czech Republic
Pt(II)/Pt(IV) complexes
Cisplatin
(diammine-dichloro-platinum(II) complex) and its analogues are known for their
high activity in the anticancer treatment. The physico-chemical background of
the activation of these drugs in the hydration process of replacing
chloro-ligards by water molecules was examined. Thermodynamic and kinetic
parameters were determined for this hydration reaction. Comparing with
experimental data it can be seen very good agreement of both characteristics. The
process of cisplatin activation can be understand purely on the thermodynamical
footings as formation of less stable Pt-complexes under the LeChatelier-Braun-van Hoff’s principle of chemical equilibrium.
Ru(II)-piano-stool complexes
Detachment
of the chloro-ligand in [Ruthenium(II)(Arene)(en)Cl]+
is studied
in connection with cisplatin activation. Similarly, transition state for
process of the water replacement was searched and both thermodynamical and
kinetical data for activation and interactions with purine nucleobases bases were
estimated. Comparison with measured data demonstrates a power of such
computational tools for further investigations.
Dinuclear Rh(II) complexes
Preference for coordination of diaqua-tetrakis-m-acetatodirhodium to purine DNA bases is examined. Higher thermodynamic affinity of the Rh-complex to guanine was found despite the larger stability of the (Rh)2-adenine structure (in accord with HSAB principle). Possible reaction mechanism for the DNA base substitution is explored using simple model molecules in the both gas phase and PCM appraoches.