Electronic structure of orotic acid I. Geometry, conformational preference and tautomerism

The molecular geometry of orotic acid was fully optimized using the gradient minimization technique. The computed geometrical parameters at the B3LYP/6-311G** level correspond well to those determined experimentally by X-ray diffraction. The relative stability of both the syn and anti conformations was investigated at the B3LYP/6-311G** level, where the syn-form was shown to be slightly more stable by 1.58 kcal/mol. The barrier to internal rotation about the C6–C12 bond was computed and this low barrier (7.655 kcal/mol) was shown to be associated with the u 1⁄4 90 conformation. The results of the present work indicate that orotic acid behaves as a free rotor in the C6–C12 bond region and both the synand anti conformations were equally probable. Fourier analysis of the internal rotation function was carried out. The results indicate that the stability of the synover the anti-form was not due to increased or tight conjugative interaction, but rather due to decreased dipole–dipole repulsion and bond moment’s interactions that is of electrostatic nature. The electronic structures of all possible tautomeric forms of orotic acid and that of its zwitterion have been thoroughly investigated. Equilibrium geometries were determined and compared to that of orotic acid. Solvent effects were taken in consideration. The self-consistent reaction field model (SCRF) was adopted to estimate gross solvent effects. The keto-form of orotic acid has been shown to be more stable than any other tautomeric forms. q 2004 Elsevier B.V. All rights reserved.