Effects of Intense Electric Fields on the Double Proton Transfer in the Watson–Crick Guanine–Cytosine Base Pair

Abstract

The double proton transfer reaction in the guanine-cytosine (GC) base pair is studied, using density functional theory, to understand the chances of mutations under the effect of uniform electric fields in the order of 10 to 10 V m. On the basis of potential energy surfaces, reaction Gibbs energies, equilibrium constants, imaginary frequencies, forward and reverse barrier heights, tunneling-corrected rate constants, half-lives of the forward and reverse reactions, percent tautomerization, and Boltzmann distributions, it was found that fields ≥+3.60 × 10 V m facilitate the mutation in the GC base pair and reduce the rectification of point mutations. Fields applied along the double proton transfer in the - x (defined in the C to G direction) direction favor the canonical over the rare tautomers. Tunneling-corrected rate constants of the forward reaction increase exponentially with stronger fields in the - x direction and follow a Gaussian curve for the reverse reaction.

The influence of base pair tautomerism on single point mutations in aqueous DNA

“…Céron-Carrasco et al [50] have shown that the inclusion of base pair stacking and explicit solvation causes the double proton transfer equilibrium constant to be smaller than that in the gas phase. In corroboration with their findings, we report equilibrium constants to be one order of magnitude smaller than recent QMonly gas phase studies that have used B3LYP/6-311++G** (1.68 × 10 −8 ) and MP2/aug-cc-pvTZ (7.5 × 10 −8 ) methods [13,15].…”

“…These are in good agreement with the values of approximately 1 kcal mol −1 computed using BP86/6-311++G** [42]. Other studies, however, reported reverse free energy barriers less than 0 kcal mol −1 using MP2/aug-cc-pVTZ and B3LYP/ 6-311++G** [13,15].…”

“…The probability of occurrence of the various double proton transfer (DPT) and single proton transfer (SPT) mechanisms observed in the ensemble QM/ MM study (sampled from 25 replicas per base pair). Recent computational studies have predicted the G:C double proton transfer equilibrium constant to be between 10 À6 and 10 À9 but this is largely dependent on the different QM approximations used [13][14][15][16]83,85]. Our results for K (approx.…”

“…The purpose of the present paper is to investigate the kinetics and thermodynamics of base pair tautomerism in a realistic DNA model. The origin of these base pair tautomers is an ongoing subject of investigation that has already been studied by idealized gas phase quantum chemical models [9][10][11][12][13][14][15][16][17][18][19]. Despite this research, proton transfer between base pairs is still not completely understood.…”

Tipping the balance: theoretical interrogation of divergent extended heterolytic fragmentations

“…44,[79][80][81] A seminal study by Shaik and co-workers demonstrated that not only can an EEF lower or raise the barrier for a Diels-Alder reaction when oriented in one direction or the other along the "reaction axis"-that is, the (approximate) axis along which electrons reorganize (on average) to make and break bonds-but an electric eld oriented perpendicular to the reaction axis can induce endo/exo selectivity. 82 The potential for EEFs to control chemical transformations has captured the curiosity of many groups [83][84][85][86][87][88][89][90][91][92] since Coote and co-workers experimentally demonstrated electrostatic catalysis of a Diels-Alder reaction in 2016. 93 For example, a recent experimental study demonstrated EEF-induced selective catalysis in a twostep reaction.…”