Interaction of 2-aminopyrimidine with dichloro-[I-alkyl-2-(naphthylazo) imidazole]palladium(II) complexes: kinetic and mechanistic studies.
BACKGROUND
The anticancer properties of cisplatin and palladium(II) complexes stem from the ability of the cis-MCl2 fragment to bind to DNA bases. However, cisplatin also interacts with non-cancer cells, mainly through bonding molecules containing -SH groups, resulting in nephrotoxicity. This has aroused interest in the design of palladium(II) complexes of improved activity and lower toxicity. The reaction of DNA bases with palladium(II) complexes with chelating N,N'donors of the cis-MCl2 configuration constitutes a model system that may help explore the mechanism of cisplatin's anticancer activity. Heterocyclic compounds are found widely in nature and are essential to many biochemical processes. Amongst these naturally occurring compounds, the most thoroughly studied is that of pyrimidine. This was one of the factors that encouraged this study into the kinetics and mechanism of the interaction of 2-aminopyrimidine (2-NH2-Pym) with dichloro-[1-alkyl-2-(alpha-naphthylazo)imidazole]palladium(II) [Pd(alpha-NaiR)Cl2, 1] and dichloro-[1-alkyl-2-(beta-naphthylazo)imidazole]palladium(II) [Pd(beta-NaiR)Cl2, 2] complexes where the alkyl R = Me (a), Et (b), or Bz (c).


RESULTS
2-NH2-Pym reacts with 1a, 1b, and 1c to yield [[1-alkyl-2-(alpha-naphthylazo)imidazole]bis(2-aminopyrimidine)]palladium(II) (3a, 3b, 3c) dichloride and with 2a, 2b, and 2c to yield [[1-alkyl-2-(beta-naphthylazo)imidazole]bis(2-aminopyrimidine)]palladium(II) (4a, 4b, 4c) dichloride in an acetonitrile (MeCN) medium. The products were characterized using spectroscopic techniques (FT-IR, UV-Vis, NMR). The ligand substitution reactions follow second order kinetics - first order dependence on the concentration of the Pd(II) complex and 2-NH2-Pym. Addition of LiCl to the reaction does not influence its rate. The thermodynamic parameters (standard enthalpy of activation, Delta(double dagger)H degrees and standard entropy of activation, Delta(double dagger)S degrees) were determined from variable temperature kinetic studies. The magnitude of the second order rate constant, k2, at 298 K, was shown to increase thus: b <a <c as well as 1 <2.


CONCLUSIONS
The kinetics of the reaction between Pd(II) complexes (1 and 2) and 2-NH2-Pym were examined spectrophotometrically at 530 nm in MeCN under pseudo-first-order conditions. The reaction rate is largely influenced by the pi-acidity of the chelating ligand, with substitution in the naphthyl azoimidazole backbone influencing the rate of the substitution process. The activation parameters, Delta(double dagger)H degrees and Delta(double dagger)S degrees, were determined and support the kinetic rate data.
Ghosh
Pradip Kumar
PK
Department of Chemistry, Jadavpur University, Kolkata, India. jupradip@yahoo.com
Saha
Sushanta
S
Mahapatra
Ambikesh
A