TAUTOMERISM OF XANTHINE-OXIDASE SUBSTRATES HYPOXANTHINE AND ALLOPURINOL

The tautomerism of neutral hypoxanthine and allopurinol in the gas pha se and in aqueous solution has been examined by theoretical methods. T he tautomeric equilibrium in the gas phase was studied from semiempiri cal and ab initio quantum mechanics (QM) and also from density functio nal theory (DFT) calculations. Electron correlation effects were inclu ded in ab initio computations at the Moller-Plesset level, and DFT cal culations were carried out using the Becke3-Lee-Yang-Parr functional. The influence of the solvent was examined from self-consistent reactio n field calculations performed with different continuum models. The re sults provide a detailed picture of the tautomerism of these biologica lly relevant compounds. Comparison with available experimental data pr ovides support for the quality of results derived from theoretical com putations. Inspection of the most stable tautomeric forms allows discu ssion of the functional implications of tautomerism for recognition an d binding of these molecules to xanthine oxidase.