Calculations of the conformational properties of acyclonucleosides. Part I. Stable conformations of acyclovir.

Conformational properties of te antiherpes agent acyclovir (acycloguanosine, ACG) were calculated using molecular mechanics approximation. Eighty two different stable conformations have been determined. The large number of local minima of the total enery, and small differences between them, point to the marked flexibility of the acyclic chain. The barrier to rotation around N9-C1 bond was calculated and found to be asymmetric (the lower equals 17 kJ/mol, the higher 63 kJ/mol). An energetic preference for the compact from of ACG was demonstrated. A comparison of the calculated conformations with the crystallographic structures is presented.