title: Solvent induced cooperativity of Zn(II) complexes cleaving a phosphate diester 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)(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.
authors: Department of Chemistry, Queen's University Kingston, Ontario, Canada K7L 3N6.
authors: Mark F
authors: MF
authors: Mohamed
authors: Irma
authors: I
authors: Sánchez-Lombardo
authors: Alexei A
authors: AA
authors: Neverov
authors: R Stan
authors: RS
authors: Brown
mesh_terms: D002384:Catalysis; D003500:Cyclization; D004952:Esters; D007700:Kinetics; D000432:Methanol / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D011199:Potentiometry; D012313:RNA / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
chemical_list: D004952:Esters; D009942:Organometallic Compounds; D010710:Phosphates; D012997:Solvents; D012313:RNA; D015032:Zinc; D000432:Methanol