Equilibrium, kinetic and HPLC study of the reactions between platinum(II) complexes and DNA constituents in the presence and absence of glutathione.
The complex formation equilibria of [Pt(SMC)(H(2)O)(2)](+) and [Pt(terpy)H(2)O](2+), where SMC =S-methyl-L-cysteine and terpy = 2,2':6',2"-terpyridine, with some biologically relevant ligands such as inosine (INO), inosine-5'-monophosphate (5'-IMP), guanosine-5'-monophosphate (5'-GMP) and glutathione (GSH) were studied. The stoichiometry and stability constants of the complexes formed are reported, and the concentration distribution of the various complex species have been evaluated as a function of pH. Also the kinetics and mechanism of the complex formation reactions were studied as a function of nucleophile concentration and temperature. For the complex [Pt(SMC)(H(2)O)(2)](+), two consecutive reaction steps, which both depend on the nucleophile concentration, were observed under all conditions. The negative entropies of activation support an associative complex formation mechanism. Reaction of guanosine-5'-monophosphate (5'-GMP) with Pt(II) complexes was carried out in the presence and absence of glutathione (GSH) at neutral pH. The rate constants clearly showed a kinetic preference toward GSH at neutral pH. The reactions were also monitored by HPLC. However, only a small amount of coordinated 5'-GMP was detected in the HPLC trace. The products were isolated and characterized by MALDI-TOF mass spectrometry.
Bugarcić
Zivadin D
ZD
University of Kragujevac, Faculty of Science, Department of Chemistry, R. Domanovića 12, P. O. Box 60, Sr-34000 Kragujevac, Serbia. bugi@kg.ac.yu
Soldatović
Tanja
T
Jelić
Ratomir
R
Algueró
Berta
B
Grandas
Anna
A
D000970:Antineoplastic Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry*; D006157:Guanosine Monophosphate / Q000737:chemistry; D007288:Inosine / Q000737:chemistry; D007291:Inosine Monophosphate / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D009944:Organoplatinum Compounds / Q000737:chemistry*
D000970:Antineoplastic Agents; D008024:Ligands; D009944:Organoplatinum Compounds; D007291:Inosine Monophosphate; D007288:Inosine; D006157:Guanosine Monophosphate; D004247:DNA; D005978:Glutathione