Kinetics and Mechanism of the Substitution Reactions of [PtCl(bpma)]+, [PtCl(gly-met-S,N,N)] and Their Aqua Analogues with L-methionine, Glutathione and 5'-GMP

Overview

Journal J Biol Inorg Chem

Publisher Springer

Specialty Biochemistry

Date 2007 Aug 22

PMID 17710451

Citations 1

Authors

Zivadin D Bugarcic

Jovana Rosic

Biljana Petrovic

Nadine Summa

Raph Puchta

Rudi van Eldik

Affiliations

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Abstract

The substitution reactions of [PtCl(bpma)]+, [PtCl(gly-met-S,N,N)], [Pt(bpma)(H(2)O)](2+) and [Pt(gly-met-S,N,N)(H(2)O)](+) [where bpma is bis(2-pyridylmethyl)amine and gly-met-S,N,N is glycylmethionine] with L-methionine, glutathione and guanosine 5'-monophosphate (5'-GMP) were studied in aqueous solutions in 0.10 M NaClO(4) under pseudo-first-order conditions as a function of concentration and temperature using UV-vis spectrophotometry. The reactions of the chloro complexes were followed in the presence of 10 mM NaCl and at pH approximately 5, whereas the reactions of the aqua complexes were studied at pH 2.5. The [PtCl(bpma)]+ complex is more reactive towards the chosen nucleophiles than [PtCl(gly-met-S,N,N)]. Also, the aqua complexes are more reactive than the corresponding chloro complexes. The activation parameters for all the reactions studied suggest an associative substitution mechanism. The reactions of [PtCl(bpma)]+ and [PtCl(gly-met-S,N,N)] with 5'-GMP were studied by using (1)H NMR spectroscopy at 298 K. The pK (a) value of the [Pt(gly-met-S,N,N)(H(2)O)]+ complex is 5.95. Density functional theory calculations (B3LYP/LANL2DZp) show that in all cases guanine coordination to the L(3)Pt fragment (L(3) is terpyridine, bpma, diethylenetriamine, gly-met-S,N,N) is much more favorable than the thioether-coordinated form. The calculations collectively support the experimentally observed substitution of thioethers from Pt(II) complexes by N7-GMP. This study throws more light on the mechanistic behavior of platinum antitumor complexes.

Citing Articles

Equilibrium Studies on Pd(II)-Amine Complexes with Bio-Relevant Ligands in Reference to Their Antitumor Activity.

Shoukry M, van Eldik R Int J Mol Sci. 2023; 24(5).

PMID: 36902279 PMC: 10003265. DOI: 10.3390/ijms24054843.

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