Tautomerism of Xanthine Oxidase Substrates Hypoxanthine and Allopurinol

The tautomerism of neutral hypoxanthine and allopurinol in the gas phase and in aqueous solution has been examined by theoretical methods. The tautomeric equilibrium in the gas phase was studied from semiempirical and ab initio quantum mechanics (QM) and also from density functional theory (DFT) calculations. Electron correlation effects were included in ab initio computations at the Møller−Plesset level, and DFT calculations were carried out using the Becke3−Lee−Yang−Parr functional. The influence of the solvent was examined from self-consistent reaction field calculations performed with different continuum models. The results provide a detailed picture of the tautomerism of these biologically relevant compounds. Comparison with available experimental data provides support for the quality of results derived from theoretical computations. Inspection of the most stable tautomeric forms allows discussion of the functional implications of tautomerism for recognition and binding of these molecules to xanthine oxidase.