title: Combination of a dinuclear Zn2+ complex and a medium effect exerts a 10(12)-fold rate enhancement of cleavage of an RNA and DNA model system.
abstract: The catalytic ability of a dinuclear Zn2+ complex of 1,3-bis-N1-(1,5,9-triazacyclododecyl)propane (3) in promoting the cleavage of an RNA model, 2-hydroxypropyl-p-nitrophenyl phosphate (HPNPP, 1), and a DNA model, methyl p-nitrophenyl phosphate (MNPP, 4), was studied in methanol solution in the presence of added CH3O- at 25 degrees C. The di-Zn2+ complex (Zn2 :3), in the presence of 1 equiv of added methoxide, exhibits a second-order rate constant of (2.75 +/- 0.10) x 10(5) M(-1) s(-1) for the reaction with 1 at s(s)pH 9.5, this being 10(8)-fold larger than the k2 value for the CH3O- promoted reaction (kOCH3 = (2.56 +/- 0.16) x 10(-3) M(-1) s(-1)). The complex is also active toward the DNA model 4, exhibiting Michaelis-Menten kinetics with a KM and kmax of 0.37 +/- 0.07 mM and (4.1 +/- 0.3) x 10(-2) s(-1), respectively. Relative to the background reactions at s(s)pH 9.5, Zn2 :3 accelerates cleavage of each phosphate diester by a remarkable factor of 1012-fold. A kinetic scheme common to both substrates is discussed. The study shows that a simple model system comprising a dinuclear Zn2+ complex and a medium effect of the alcohol solvent achieves a catalytic reactivity that approaches enzymatic rates and is well beyond anything seen to date in water for the cleavage of these phosphate diesters.
authors.affiliation: Department of Chemistry, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Neverov
authors.forename: Zhong-Lin
authors.initials: ZL
authors.lastname: Lu
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Maxwell
authors.forename: Mark F
authors.initials: MF
authors.lastname: Mohamed
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: White
authors.forename: Josephine S W
authors.initials: JS
authors.lastname: Tsang
authors.forename: R Stan
authors.initials: RS
authors.lastname: Brown
mesh_terms: D002413:Cations, Divalent / Q000737:chemistry; D003500:Cyclization; D004247:DNA / Q000737:chemistry*; D007700:Kinetics; D008697:Methane / Q000737:chemistry; D008954:Models, Biological; D015394:Molecular Structure; D012313:RNA / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
chemical_list: D002413:Cations, Divalent; D012313:RNA; D004247:DNA; D015032:Zinc; D008697:Methane