A reductionist biomimetic model system that demonstrates highly effective Zn(II)-catalyzed cleavage of an RNA model.
The cyclization of the RNA model 2-hydroxypropyl p-nitrophenyl phosphate (HPNPP, 1) promoted by Zn2+ alone and the 1,5,9-triazacyclododecane complex of Zn2+ (Zn2+:[12]aneN3) is studied in ethanol in the presence of 0.5 equiv of -OEt/Zn2+ to investigate the effect of a low polarity/dielectric medium on a metal-catalyzed reaction of biological relevance. Ethanol exerts a medium effect that promotes strong binding of HPNPP to Zn2+, followed by a dimerization to form a catalytically active complex (HPNPP:Zn2+)2 in which the phosphate undergoes cyclization with a rate constant of kcat = 2.9 s(-1) at s(s)pH 7.1. In the presence of the triaza ligand:Zn2+ complex, the change from water to methanol and then to ethanol brings about a mechanism where two molecules of the complex, suggested as EtOH:Zn2+:[12]aneN3 and its basic form, EtO-:Zn2+:[12]aneN3, bind to HPNPP and catalyze its decomposition with a rate constant of kcat of 0.13 s(-1) at s(s)pH 7.1. Overall, the acceleration exhibited in these two situations is 4 x 10(14)-fold and 1.7 x 10(12)-fold relative to the background ethoxide-promoted reactions at the respective s(s)pH values. The implications of these findings are discussed within the context of the idea that enzymatic catalysis is enhanced by a reduced effective dielectric constant within the active site.
Liu
C Tony
CT
Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, Ontario, Canada.
Neverov
Alexei A
AA
Brown
R Stan
RS
D032701:Biomimetics / Q000379:methods*; D002384:Catalysis; D003500:Cyclization; D000431:Ethanol / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D015394:Molecular Structure; D009596:Nitrophenols / Q000138:chemical synthesis / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D010755:Organophosphates; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D012680:Sensitivity and Specificity; D015032:Zinc / Q000737:chemistry*
C436487:2-(hydroxypropyl)-4-nitrophenyl phosphate; D009596:Nitrophenols; D009942:Organometallic Compounds; D010755:Organophosphates; D009943:Organophosphorus Compounds; D000431:Ethanol; D015032:Zinc; D000432:Methanol; C024836:4-nitrophenol