Equilibrium and kinetic studies of the aquation of the dinuclear platinum complex [{trans-PtCl(NH3)2}2(μ-NH2(CH2)6NH2)2+: pK(a) determinations of aqua ligands via [1H,15N] NMR spectroscopy

Abstract

By the use of [1H,15N] heteronuclear single quantum coherence (HSQC) 2D NMR spectroscopy and electrochemical methods we have determined the hydrolysis profile of the bifunctional dinuclear platinum complex [{trans-PtCl(15NH3)2}2(μ-15NH2(CH2)615NH2)]2+ (1,1/t,t (n=6), 15N-1), the prototype of a novel class of potential antitumor complexes. Reported are estimates for the rate and equilibrium constants for the first and second aquation steps, together with the acid dissociation constant (pK(a)1 ≃ pK(a)2 ≃ pK(a)3). The equilibrium constants determined by NMR at 25 and 37 °C (I = 0.1 M) were similar, pK1 ≃ pK2 = 3.9 ± 0.2, and from a chloride release experiment at 37 °C the values were found to be pK1 = 4.11 ± 0.05 and pK2 = 4.2 ± 0.5. The forward and reverse rate constants for aquation determined from this chloride release experiment were k1 = (8.5 ± 0.3) x 10-5 s-1 and k-1 = 0.91 ± 0.06 M-1 s-1, where the model assumed that all the liberated chloride came from 1. When the second aquation step was also taken into account, the rate constants were k1 = (7.9 ± 0.2) x 10-5 s-1, k-1 = 1.18 ± 0.06 M-1 s-1, k2 = (10.6 ± 3.0) x 10-4 s-1, k-2 = 1.5 ± 0.6 M-1 s-1. The rate constants compare favorably with other complexes with the [PtCl(am(m)ine)3]+ moiety and indicate that the equilibrium of all these species favors the chloro form. A PK(a) value of 5.62 was determined for the diaquated species [{trans-Pt(15NH3)2(H2O)}2(μ-15NH2(CH2)615NH2)]4+ (3) using [1H, 15N] HSQC NMR spectroscopy. The speciation profile of 1 and its hydrolysis products under physiological conditions is explored.