A DFT study on protic solvent assisted tautomerization of heterocyclic thiocarbonyls

Thione-thiol tautomerization is biologically and synthetically significant proton transfer reaction. Current study analyses the effect of protic solvents on this reaction involving heterocyclic thiocarbonyl compounds having potent bioactivities such as 1,3-dihydroimidazole-2-thione, 2-thiohydantoin and 2-thiouracil. The computed catalytic effect of polar protic solvents water and methanol is explained by the favorable lone pair - antibonding orbital interactions which facilitates the required proton transfer. Microhydration study up to six water molecules has been carried out to get more insight into the explicit water-solute interaction. It has been concluded that four water molecules are enough to model explicit water-solute interaction that favorably affects the tautomerism of heterocyclic thiocarbonyl compounds. Moreover, the thione formation step of the equilibrium gets relatively more facilitated by the polar protic solvents. The results are further validated by considering a reported thiol-thione conversion in enzymatic decarboxylation reaction of 4'-phosphopantothenoylcysteine.