Stereoelectronic properties of five anti-HSV-1 2'-deoxynucleosides analogues with heterocyclic substituents in the 5-position: a comparison with BVDU.

Structural and electronic characteristics of 5-(5-chlorothien-2-yl)-2'-deoxyuridine (I), 5-(furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofuran-2-yl)-2'-deoxyuridine (III), 5-(3-bromoisoxazol-5-yl)-2'-deoxyuridine (V) and 5-(isoxazol-5-yl)-2'-deoxyuridine (IV) have been determined and compared to the BVDU (VI) characteristics in order to explain their respective affinity for the herpes simplex virus type 1 thymidine kinase (TK). Molecular structure of 5-(5-chlorothien-2-yl)-2'-deoxyuridine has been obtained using single crystal X-ray crystallography. Electrostatic potential maps, energy and topology of frontier orbitals were computed at the ab initio MO STO-3G and STO-3G level. These studies reveal that the electrostatic potential energy maps are clearly dependent on the affinity of the compound for the enzyme.