Quantum mechanical analysis of nonenzymatic nucleotidyl transfer reactions: kinetic and thermodynamic effects of β-γ bridging groups of dNTP substrates.

ABSTRACT: Rate (k) and equilibrium (K) constants for the reaction of tetrahydrofuranol with a series of Mg(2+) complexes of methyl triphosphate analogues, CH3O-P(O2)-O-P(O2)-X-PO3(4-), X = O, CH2, CHCH3, C(CH3)2, CFCH3, CHF, CHCl, CHBr, CFCl, CF2, CCl2, and CBr2, forming phosphate diester and pyrophosphate or bisphosphonate in aqueous solution were evaluated by B3LYP/TZVP//HF/6-31G* quantum chemical calculations and Langevin dipoles and polarized continuum solvation models. The calculated log k and log K values were found to depend linearly on the experimental pKa4 of the conjugate acid of the corresponding pyrophosphate or bisphosphonate leaving group. The calculated slopes of these Brønsted linear free energy relationships were βlg = -0.89 and βeq = -0.93, respectively. The studied compounds also

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC4081047 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature