Solvent effects in density functional calculations of uracil and cytosine tautomerism

Abstract

mThe effects of the solvent on the tautomeric equilibria of cytosine and uracil are studied using Onsager's reaction field model in the framework of density functional theory. In this model, the solute molecule is placed in a spherical cavity of radius a, immersed in a continuous medium with a dielectric constant E , treating the solute-solvent electrostatic interactions at the dipole level. The cavity radius is evaluated by determining the molecular volume with a quantum mechanical approach. The solvent effect brings significant changes in the geometrical parameters of some cytosine tautomers, but only very small changes to those of the uracil tautomers. Our results are in good agreement with available experimental results and confirm that the polarization of the solute by the continuum has important effects on the absolute and relative solvation energies. Frequency shifts and intensity variations in the infrared spectra due to the presence of the solvent are also presented. 0 1995 John Wiley & Sons, Inc.tomers may have important biological implications, such as mutagenesis. In addition, the effect of the environment on tautomeric equilibria may be dramatic, changing equilibrium constants several orders of magnitude. Recently, we reported gas-phase calculations on the tautomerism of uracil and cytosine molecules [9] using density functional theory (DFT); the results are in reasonable agreement with the avail-

Structures, stabilities and tautomerizations of uracil and diphosphouracil tautomers

“…At B3LYP/6-31+G ** level of theory, the most stable tautomer is 1,3-U, followed by 2 1 ,3-U, 1,4 1 -U, 2 1 ,4 1 -U, 2 2 ,4 1 -U, 2 1 ,4 2 -U, 2 2 ,4 2 -U, 1,4 2 -U, 2 2 ,3-U, 1,2 2 -U, 3,4 2 -U, 3,4 1 -U, and 1,2 1 -U. This order is consistent with former studies [30,35,42]. High level ab initio methods give not only considerable differences in relative energy values, but also change the stability order [51].…”

Protonation of thymine, cytosine, adenine, and guanine DNA nucleic acid bases: Theoretical investigation into the framework of density functional theory

“…Similar behaviors have been found at the MP2 30 level and with previous DF computations on cytosine. 6 In the protonated molecules the amine groups are nearly planar. As a general feature we note that our bond lengths and valence angles agree well with the experimental data and are consistent with MP2-optimized structures.…”

“…In fact, the most stable DF tautomer is always the one with the hydrogen bonded to the nitrogen to which the sugar moiety of nucleosides is attached. On the other hand, in the case of cytosine, the energy differences between the most stable tautomer proposed by the ab initio study 3 and that coming from the previous DF computation 6 is about 1 kcalrmol and does not significantly affect the PA values.…”

“…Although in one 3,6 . case i.e., cytosine there is no correspondence between DF and ab initio-correlated methods in the prediction of tautomeric relative stabilities, we believe that our choice is the better one from a biological point of view.…”

An ab initio theoretical study of electronic structure and properties of 2′‐deoxyguanosine in gas phase and aqueous media

“…[3][4][5][6] Vigorous efforts are being made to understand the structures and properties of a variety of biomolecules including the nucleic acid bases using theoretical and spectroscopic methods. [3][4][5][6][7][8][9][10][11][12] Electronic structure calculations, 13,14 simulation, 15,16 and studies of solvent effects [17][18][19][20] have been carried out on several systems, including the nucleic acid bases and other biologically important molecules. It is found that behaviors of biomolecules in aqueous media may be appreciably different from those in crystals.…”