Molecular‐orbital studies of the mechanism of xanthine oxidase‐catalyzed oxidation of purines, especially 2‐chloropurine

A detailed study to the xanthine oxidase‐catalyzed reactions of 2‐chloropurine and other substrate bases with various molecular‐orbital techniques such as HMO, ω‐SCFHMO, and ppp semiempirical SCFLCAOMO has shown that the enzyme reactions can be understood in terms of electronic reactivity indices. Furthermore, it appeared possible to suggest the enzyme specificity from a systematic analysis of discrepancy between mo theoretically predicted and observed reaction sites in substrates with 2‐ and 8‐oxy substituents. In other words, the discrepancy does not necessarily indicate the failure of the MO melthodes for such substrates, but it is possible to utilize the result in correlating with binding specificity of the ES complex. This has been done specifically for 2‐chloropurine. Among several electronic reacxtivity indices, frontier orbital density, superdelocalizability, and localization energy have been proved to be very useful. Diferent MO methods gave, in general, consistent results.