STEREOELECTRONIC PROPERTIES OF 5 ANTI-HSV-1 2'DEOXYNUCLEOSIDES ANALOGS WITH HETEROCYCLIC SUBSTITUENTS IN THE 5-POSITION - A COMPARISON WITHBVDU

Structural and electronic characteristics of 5-(5-chlorothien-2-yl)-2' -deoxyuridine (I), 5-(furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofura n-2-yl)-2'-deoxyuridine (III), 5-(3-bromoisoxazol-5-yl)-2'-deoxyuridin e (V) and 5-(isoxazol-5-yl)-2'-deoxyuridine (IV) have been determined and compared to the BVDU (VI) characteristics in order to explain thei r respective affinity for the herpes simplex virus type 1 thymidine ki nase (TK). Molecular structure of 5-(5-chlorothien-2-yl)-2'-deoxyuridi ne has been obtained using single crystal X-ray crystallography. Elect rostatic potential maps, energy and topology of frontier orbitals were computed at the ab initio MO STO-3G and STO-3G level. These studies r eveal that the electrostatic potential energy maps are clearly depende nt on the affinity of the compound for the enzyme.