Solvent induced cooperativity of Zn(ii) complexes cleaving a phosphate diester RNA analog in methanolElectronic supplementary information (ESI) available: Tables and Figures giving various kobsvs. [catalyst] rate constant data for cleavage of 1 as well as the 1H NMR spectrum of 4. See DOI: 10.1039/c1ob06482g

• Main Authors: Mohamed, Mark F, Snchez-Lombardo, Irma, Neverov, Alexei A, Brown, R. Stan
• Format: Journal Article
• Language: English
• Published: 15.12.2011
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c1ob06482g

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 s pH-controlled conditions (where s s pH refers to [H + ] activity in methanol). Potentiometric titrations of the ligands in the absence and presence of Zn 2+ 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 :( OCH 3 ) or a bound deprotonated form of the phosphate, L :Zn( ii ): 6 2 . 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 s pH 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 s pH 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. Mononuclear 4 :Zn( ii ) and 5 :Zn( ii ) promote transesterification of HPNPP in methanol forming L :Zn( ii ): 1 , followed by cooperative interaction with a second L :Zn( ii ).