Kinetic and Mechanistic Aspects of Ligand Substitution on cis- Diaqua (cis-1,2-Diaminocyclohexane)Platinum(II) with Three Glycine-Containing Dipeptides

Abstract

The kinetics of the interaction of glycyl-L-valine(L1-L′H), glycyl-L-isoleucine (L2-L′H) and glycyl-L-glutamine(L3-L′H) with cis-[Pt( cis-dach)(OH2)2]2+ (dach = 1,2-diaminocyclohexane) have been studied spectrophotometrically as a function of [ cis-[Pt( cis-dach)(OH2)2]2+], [ligand], pH and temperature at constant ionic strength, where the complex exists predominantly as the diaqua species and the dipeptides as a zwitterion. The substitution reactions show two consecutive steps: the initial is the ligand-assisted anation and the subsequent step is chelation. The activation parameters for both steps were evaluated using Eyring's equation. The low DL H1 ≠ and large negative value of Δ S1 ≠ as well as Δ H2 ≠ and Δ S2 ≠ indicate an associative mode of activation for both the aqua ligand substitution processes. The products of the reactions have been characterised using IR and ESI-mass spectroscopic analysis. The title complex is already established as an anticancer drug; but its reactivity with all biomolecules will confirm its therapeutic activity (i.e. its efficacy versus toxicity).