Solvent induced cooperativity of Zn(ii) complexes cleaving a phosphatediester RNA analog in methanol

Abstract

The kinetics of cyclization of 2-hydroxypropyl p-nitrophenyl phosphate (1) promoted by two mononuclear Zn(II) catalytic complexes of bis(2-pyridylmethyl)benzylamine (4) and bis(2-methyl 6-pyridylmethyl)benzylamine (5) in methanol were studied under ^s_spH-controlled conditions (where ^s_spH refers to [H⁺] activity in methanol). Potentiometric titrations of the ligands in the absence and presence of Zn²⁺ and a non-reactive model for 1 (2-hydroxylpropyl isopropyl phosphate (HPIPP, 6)) indicate that the phosphate is bound tightly to the 4:Zn(II) and 5:Zn(II) complexes as L:Zn(II):6⁻, and that each of these undergoes an additional ionization to produce L:Zn(II):6⁻:(⁻OCH₃) or a bound deprotonated form of the phosphate, L:Zn(II):6²⁻. Kinetic studies as a function of [L:Zn(II)] indicate that the rate is linear in [L:Zn(II)] at concentrations well above those required for complete binding of the substrate. Plots of the second order rate constants (defined as the gradient of the rate constant vs. [complex] plot) vs.^s_spH in methanol are bell-shaped with rate maxima of 23 dm mol⁻¹ s⁻¹ and 146 dm mol⁻¹ s⁻¹ for 4:Zn(II) and 5:Zn(II), respectively, at their ^s_spH maxima of 10.5 and 10. A mechanism is proposed that involves binding of one molecule of complex to the phosphate to yield a poorly reactive 1 : 1 complex, which associates with a second molecule of complex to produce a transient cooperative 2 : 1 complex within which the cyclization of 1 is rapid. The observations support an effect of the reduced polarity solvent that encourages the cooperative association of phosphate and two independent mononuclear complexes to give a reactive entity.