Spectroscopic investigation of the tautomeric equilibria in the guanine derivatives of acyclovir

Abstract

The effect of solvent polarity on the keto–enol tautomerism of N- and O-acetylated acyclovir derivatives has been studied. Results of different spectroscopic methods (¹H NMR, UV/VIS, IR, Raman) have been interpreted in combination with the results of semi-empirical calculations and by comparison with two derivatives of deoxyacyclovir. From the UV/VIS spectra it was found that the keto–enol equilibrium in acyclovir is strongly dependent on the solvent polarity; in methylene chloride the enol form was observed, whereas in water the keto form dominates. However, acetylation on the N terminal function stabilises the keto tautomer in all tested solvents, due to the formation of an intramolecular hydrogen bond between the acetyl CO function and H(¹N). Substitution on the OH group in the side function does not influence the tautomeric equilibrium but changes the polarity of the substance and makes it almost insoluble in apolar solvents such as methylene chloride.