Solvation and solid state effects on the structure and energetics of the tautomers of creatinine

The tautomeric equilibrium involving the amine and imine forms of creatinine are studied theoretically in both the gas phase, the aqueous environment, and the solid state. High level ab initio calculations predict the imine form to be preferred in the gas phase by 2.0 kcal mol−1. In the aqueous environment, both continuum and explicit solvent models predict the amine form to be the most stable, with solute polarization being an important contributing factor. An embedding procedure is used to model solid state effects when again the amine is preferred, in agreement with experimental crystallographic studies. The predicted solid state molecular geometry is compared to the experimental structure.