The effect of methylation on the structure of uracil

Abstract

Equilibrium geometries of uracil, 1-methyluracil and 3-methyluracil (in which the methyl group is attached to nitrogen), 5-methyluracil (thymine) and 6-methyluracil (in which the methyl group is attached to carbon), 1,3-dimethyluracil and 5,6-dimethyluracil have been determined by ab initio Hartree-Fock calculations with the split-valence 4-21G basis set. For the methylated derivatives, calculations are made for different conformations corresponding to different orientations of the methyl groups. The conformational energy differences are small, indicating a very low barrier to internal rotation, except for 5- and 6-methyluracils in which there is a preference of 1–2kcal mol −1 for the conformer with the methyl CH bond eclipsing the double bond of the ring. The structural differences between the methylated uracils and the parent molecule are analyzed. Angular deformations within the ring induced by substitution of a methyl group for hydrogen follow, to a rough approximation, the trends established earlier for benzene derivatives on the basis of X-ray studies. Deviations occur due to the difference between nitrogen and carbon in the ring, with deformations being more pronounced for N- than for C-substituted uracils. The methyl groups, in general, show a distinct tilt away from an adjacent carbonyl group, indicating a repulsive interaction. Mulliken population analysis shows the electronegative methyl group withdraws charge mainly from the atom to which it is attached and, to at least as great an extent, from the adjacent ring atoms. The results are compared with those obtained earlier by the semiempirical MINDO 3 method and also by different experimental techniques including X-ray, neutron, and electron diffraction. These other studies have given much information on the structure of the compounds, but because of their nature they have not been able to analyze detailed structural variations induced by the methyl group substitution.