Snežana Jovanović

Interactions of nitrogen-donor bio-molecules with dinuclear platinum(II) complexes

Substitution reactions of the dinuclear Pt(II) complexes, [{Pt(en)Cl}2(μ-pz)]2+ (1), [{Pt(dach)Cl}2(μ-pz)]2+ (2) and [{Pt(dach)Cl}2(μ-4,4ʹ-bipy)]2+ (3), and corresponding aqua analogs with selected biologically important ligands, viz. 1,2,4-triazole, L-histidine (L-His) and guanosine-5ʹ-monophosphate (5ʹ-GMP) were studied under pseudo-first-order conditions as a function of concentration and temperature using UV–vis spectrophotometry. The reactions of the chloride complexes were followed in aqueous 25 mmol L−1 Hepes buffer in the presence of 40 mmol L−1 NaCl at pH 7.2, whereas the reactions of the aqua complexes were studied at pH 2.5. Two consecutive reaction steps, which both depend on the nucleophile concentration, were observed in all cases. The second-order rate constants for both reaction steps indicate a decrease in the order 1 > 2 > 3 for all complexes. Also, the pKa values of all three aqua complexes were determined. The order of the reactivity of the studied ligands is 1,2,4-triazole > L-His > 5ʹ-GMP. 1H NMR spectroscopy and HPLC were used to follow the substitution of chloride in the dichloride 1, 2, and 3 complexes by guanosine-5ʹ-monophosphate (5ʹ-GMP). This study shows that the inert and bridging ligands have an important influence on the reactivity of the studied complexes. Graphical Abstract

UV-Vis, HPLC, and 1H-NMR studies of the substitution reactions of some Pt(IV) complexes with 5′-GMP and L-histidine

Substitution reactions of [PtCl4(en)] and [PtCl4(dach)] with guanosine-5′-monophosphate (5′-GMP) and L-histidine were studied by different experimental methods. By UV-Vis spectrophotometry, these reactions were investigated under pseudo-first-order conditions at 310 K in 25 mmol Hepes buffer (pH = 7.2) and 10 mmol NaCl to prevent the hydrolysis of the complexes. [PtCl4(en)] reacts slightly faster than the [PtCl4(dach)]. Also, L-histidine is a better nucleophile than 5′-GMP. Final 1H-HMR spectra of the substitution of Pt(IV) were in a good agreement with the spectra of Pt(II) complexes with the same nucleophiles, confirming the assumption of the reduction of Pt(IV) complexes during substitution. The same reactions were studied by high-performance liquid chromatography comparing the chromatograms during the reaction. The changes in the intensity of signals and their retention time show that at the end of substitution, there is only one dominant product in the system. We conclude that substitution of these Pt(IV) complexes is followed by rapid reductive elimination and final product is substituted Pt(II) complex.

Crystal structure of K[PtCl3(caffeine)] and its interactions with important nitrogen-donor ligands

Abstract The crystal structure of K[PtCl3(caffeine)] was determined. The coordination geometry around platinum is square-planar formed by N9 of the caffeine ligand and three Cl− ions. The bond lengths and angles of K[PtCl3(caffeine)] were compared with those reported for [PtCl3(caffeine)]− and K[PtCl3(theobromine)]. At the level of the statistical significance of the data we have compared, no differences in the bond distances and angles for any of these compounds were noticed. Weak interactions between K+ and Cl− are responsible for the formation of 1-D polymeric chains in the crystal structure of the complex. The interactions of K[PtCl3(caffeine)] with inosine (Ino) and guanosine-5′-monophosphate (5′-GMP) were studied by 1H NMR spectroscopy at 295 K in D2O in a molar ratio of 1 : 1. The results indicate formation of the reaction product [PtCl3(Nu)] (Nu=Ino or 5′-GMP) with the release of caffeine from the coordination sphere of the starting complex. The higher stability of the bond between the Pt(II) ion and Ino or 5′-GMP compared to the stability of the platinum–caffeine bond is confirmed by density functional theory calculations (B3LYP/LANL2DZp) using as models 9-methylhypoxanthine and 9-methylguanine.

Kinetics and mechanism of the substitution reactions of some monofunctional Pt(II) complexes with heterocyclic nitrogen donor molecules. Crystal structure of [Pt(bpma)(pzBr)]Cl2·2H2O

Abstract Substitution reactions of [Pt(terpy)Cl]+ (terpy = 2,2′;6′,2′′-terpyridine), [Pt(bpma)Cl]+ (bpma = bis(2-pyridylmethyl)amine), [Pt(dien)Cl]+ (dien = diethylenetriamine or 1,5-diamino-3-azapentane) and [Pt(tpdm)Cl]+ (tpdm = tripyridinedimethane) with nitrogen donor heterocyclic molecules, such as 3-amino-4-iodo-pyrazole (pzI), 5-amino-4-bromo-3-methyl-pyrazole (pzBr) and imidazole (Im), were studied in aqueous 0.10 M NaClO4 in the presence of 10 mM NaCl using variable-temperature UV–vis spectrophotometry. The second-order rate constants k2 indicate decrease in reactivity in the order [Pt(terpy)Cl]+ > [Pt(bpma)Cl]+ > [Pt(tpdm)Cl]+ > [Pt(dien)Cl]+. The most reactive nucleophile among the heterocyclic compounds is imidazole, while pzI shows slightly higher reactivity than pzBr. Activation parameters were also determined and the negative values for entropies of activation, ΔS≠, support an associative mode of substitution for all substitution processes. Crystal structure of [Pt(bpma)(pzBr)]Cl2·2H2O was determined by single-crystal X-ray analysis. The coordination geometry of the complex is distorted square-planar while the bond distance Pt–N2(pzBr) is longer than the other three Pt–N distances.