Étude cinétique et thermodynamique de l'interaction d'un complexe de Pd(II) avec l'inosine et l'acide polyinosinique

Abstract

R e p le 26 mai 1987ROBERT M~N A R D et MIKLOS ZADOR. Can. J. Chem. 66, 178 (1988). Les rCactions du complexe (dien)Pd(II) avec I'inosine et I'acide polyinosinique ont Ct C CtudiCes a I'aide de mtthodes spectroscopiques et de flux-stoppC. Dans les deux cas, le metal se lie initialement au site N7 de la base hypoxanthine. Les rCsultats des etudes cinCtiques indiquent que le mecanisme implique deux voies rCactionnelles : une substitution nuclkophile directe ainsi qu'une reaction via un intermediaire aquo. Les rCactions sont plus rapides dans le cas du poly(I), due a la forte densit6 de charges nCgatives de ce polymkre. La rCaction initiale au site N7 est suivie d'une redistribution lente du metal vers le site NI thermodynamiquement plus stable. La fixation du (dien)Pd(II) au poly(1) induit la formation d'une structure multi-hClicoi'dale stable du polymkre. Cette structure a Ct C caractCrisCe par des mesures d'absorbance et de dichroi'sme circulaire ainsi que par la dktermination de la courbe de fusion du polymkre. I1 a aussi Ct C observC qu'en prCsence du complexe de Pd(II), le poly(1) peut Ctre hydrolysC B pH alcalin, dans des conditions relativement douces.ROBERT M~N A R D and MIKLOS ZADOR. Can. J. Chem. 66, 178 (1988) Reactions of the (dien)Pd(II) complex with inosine and polyinosinic acid were studied by spectroscopic and stopped-flow methods. In both cases, the metal initially binds at the N7 site of the hypoxanthine base. The results of kinetic studies indicate the existence of a two-path mechanism: a direct nucleophilic substitution and a solvent path with formation of an aquo intermediate. The reactions are faster for poly(I), due to the high density of negative charges for this polymer. The initial reaction at N7 is followed by a slow redistribution of the metal towards the thermodynamically more stable N I site. Binding of (dien)Pd(II) to poly(1) leads to formation of a stable, multistranded helicoidal structure of the polymer. This structure was characterized by absorption and circular dichroism measurements and by the melting curve of the polymer. It was also observed that in presence of the Pd(I1) complex, poly(1) can be hydrolyzed at relatively mild conditions at high pH.

Medium Effects on Reactivity Profiles for Platination of Phosphorothioate-Containing Oligonucleotides

“…For example, the apparent rate for thermal electron transfer and substitution reactions 20-30 of freely diffusing cationic metal complexes with various reactants has been found to increase in a polymeric DNA environment. For the latter type of reactions, the composition of the reaction medium and the detailed DNA environment have been shown to have a large influence on the observed rate constants. − Systematic studies of interactions between positively charged metal complexes of Pt(II), Pd(II), and Au(III) and target sites incorporated into short poly-d(T) oligomers have revealed a DNA-promoted effect in reactivity range spanning 6 orders of magnitude, when compared with reference reactions of monomers such as d(Tp(S)T), d(GpG), d( s4 U), and d( s6 I). ,,− , Further, the dependence of the observed rate constants on the concentration of neutral salts in the reaction medium, which has been observed for some of these systems, fits qualitatively well with a reaction mechanism in which electrostatic preaccumulation of the cationic reactants on the oligomer takes place prior to the rate-determining formation of the adduct. , However, a detailed mechanistic interpretation of the salt dependence is hampered by a lack of more precise knowledge concerning the extent and dynamics of associated cations around the used oligonucleotide fragments …”

“…The ability of DNA to modulate transition metal reactivity has been observed in several studies. For example, the apparent rate for thermal electron transfer 19 and substitution reactions [20][21][22][23][24][25][26][27][28][29][30] of freely diffusing cationic metal complexes with various reactants has been found to increase in a polymeric DNA environment. For the latter type of reactions, the composition of the reaction medium and the detailed DNA environment have been shown to have a large influence on the observed rate constants.…”

“…For the latter type of reactions, the composition of the reaction medium and the detailed DNA environment have been shown to have a large influence on the observed rate constants. [22][23][24][25][26][27][28][29][30][31][32] Systematic studies of interactions between positively charged metal complexes of Pt(II), Pd(II), and Au(III) and target sites incorporated into short poly-d(T) oligomers have revealed a DNA-promoted effect in reactivity range spanning 6 orders of magnitude, when compared with reference reactions of monomers such as d(Tp(S)T), d(GpG), d( s4 U), and d( s6 I). 24,25,[28][29][30]33 Further, the dependence of the observed rate constants on the concentration of neutral salts in the reaction medium, which has been observed for some of these systems, fits qualitatively well with a reaction mechanism in which electrostatic preaccumulation of the cationic reactants on the oligomer takes place prior to the rate-determining formation of the adduct.…”