Prediction of tautomeric preferences and pK_a values for oxyluciferin and its constituent heterocycles

Well converged electronic structure calculations are employed to predict the relative energies of tautomers of thiazol-5(4H)-one/5-hydroxythiazole. Benchmarks established for this system are then employed to correct less complete levels of theory applied to the prediction of relative tautomer energies in substituted cases, including oxyluciferin. In the gas phase and aqueous solution, weak preferences for hydroxy and keto tautomers, respectively, are generally observed, but the magnitude is such that mixtures containing significant quantities of minor tautomers are predicted in most instances. The first pK_a value for oxyluciferin is predicted to be 6.5, with phenolate tautomers dominating the anionic equilibrium.