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Interaction of 2-aminopyrimidine with dichloro-[I-alkyl-2-(naphthylazo) imidazole]palladium(II) complexes: kinetic and mechanistic studies.

Ghosh PK, Saha S, Mahapatra A - Chem Cent J (2007)

Bottom Line: Heterocyclic compounds are found widely in nature and are essential to many biochemical processes.Addition of LiCl to the reaction does not influence its rate.The activation parameters, Delta(double dagger)H degrees and Delta(double dagger)S degrees, were determined and support the kinetic rate data.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Chemistry, Jadavpur University, Kolkata, India. jupradip@yahoo.com

ABSTRACT

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

Conclusion: 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.

No MeSH data available.


Spectra of Pd(α-NaiEt)Cl2 in MeCN and the reaction mixture of Pd(α-NaiEt)Cl2 and 2-NH2-Pym in MeCN solution at 298 K. The arrows indicate decrease and increase of band intensities over the course of the reaction.
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Figure 7: Spectra of Pd(α-NaiEt)Cl2 in MeCN and the reaction mixture of Pd(α-NaiEt)Cl2 and 2-NH2-Pym in MeCN solution at 298 K. The arrows indicate decrease and increase of band intensities over the course of the reaction.

Mentions: For the kinetic measurements, stock solutions of the Pd(II) complexes (ca. 10-3 mol dm-3) and of 2-amino-pyrimidine (2-NH2-Pym) (ca. 10-2 mol dm-3) were prepared in dry MeCN. Solutions of different concentrations were prepared by quantitatively diluting stock solutions using dry MeCN. All experiments were performed at 298 K (unless otherwise stated) by mixing the required volumes of the thermostated reactants, before being transferred into the absorption cells (1.0 cm length). On addition of 2-amino-pyrimidine (2-NH2-Pym) to the solution of Pd(N,N/)Cl2 (1 or 2) in MeCN the orange solution changes to yellow-orange. The influence of the addition of 2-amino-pyrimidine (2-NH2-Pym) on the spectra of Pd(α-NaiEt)Cl2 (1b) is shown in the Figure 7. The change proceeds through a single isosbestic point at ca. 412 nm. The decrease in absorbance of the reaction mixture was recorded automatically at ca. 530 nm as a function of time. A∞ was measured after ~24 h of mixing, when the absorbance became constant. In all experiments, the initial molar concentration of 2-NH2-Pym, [2-NH2-Pym]0 was kept at least ten times higher than Pd(II) complex concentration so as to maintain pseudo-first-order kinetic conditions. Pseudo-first-order rate constants, kobs, were obtained from the slopes of the plots of (At-A∞) versus time (Figure 8) where At = absorbance of the reaction mixture at time, t(s) after mixing of 2-NH2-Pym solution, and A∞ = absorbance of same after completion of the reaction.


Interaction of 2-aminopyrimidine with dichloro-[I-alkyl-2-(naphthylazo) imidazole]palladium(II) complexes: kinetic and mechanistic studies.

Ghosh PK, Saha S, Mahapatra A - Chem Cent J (2007)

Spectra of Pd(α-NaiEt)Cl2 in MeCN and the reaction mixture of Pd(α-NaiEt)Cl2 and 2-NH2-Pym in MeCN solution at 298 K. The arrows indicate decrease and increase of band intensities over the course of the reaction.
© Copyright Policy
Related In: Results  -  Collection

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Figure 7: Spectra of Pd(α-NaiEt)Cl2 in MeCN and the reaction mixture of Pd(α-NaiEt)Cl2 and 2-NH2-Pym in MeCN solution at 298 K. The arrows indicate decrease and increase of band intensities over the course of the reaction.
Mentions: For the kinetic measurements, stock solutions of the Pd(II) complexes (ca. 10-3 mol dm-3) and of 2-amino-pyrimidine (2-NH2-Pym) (ca. 10-2 mol dm-3) were prepared in dry MeCN. Solutions of different concentrations were prepared by quantitatively diluting stock solutions using dry MeCN. All experiments were performed at 298 K (unless otherwise stated) by mixing the required volumes of the thermostated reactants, before being transferred into the absorption cells (1.0 cm length). On addition of 2-amino-pyrimidine (2-NH2-Pym) to the solution of Pd(N,N/)Cl2 (1 or 2) in MeCN the orange solution changes to yellow-orange. The influence of the addition of 2-amino-pyrimidine (2-NH2-Pym) on the spectra of Pd(α-NaiEt)Cl2 (1b) is shown in the Figure 7. The change proceeds through a single isosbestic point at ca. 412 nm. The decrease in absorbance of the reaction mixture was recorded automatically at ca. 530 nm as a function of time. A∞ was measured after ~24 h of mixing, when the absorbance became constant. In all experiments, the initial molar concentration of 2-NH2-Pym, [2-NH2-Pym]0 was kept at least ten times higher than Pd(II) complex concentration so as to maintain pseudo-first-order kinetic conditions. Pseudo-first-order rate constants, kobs, were obtained from the slopes of the plots of (At-A∞) versus time (Figure 8) where At = absorbance of the reaction mixture at time, t(s) after mixing of 2-NH2-Pym solution, and A∞ = absorbance of same after completion of the reaction.

Bottom Line: Heterocyclic compounds are found widely in nature and are essential to many biochemical processes.Addition of LiCl to the reaction does not influence its rate.The activation parameters, Delta(double dagger)H degrees and Delta(double dagger)S degrees, were determined and support the kinetic rate data.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Chemistry, Jadavpur University, Kolkata, India. jupradip@yahoo.com

ABSTRACT

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

Conclusion: 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.

No MeSH data available.


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