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

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