Molecular orbital studies on nucleoside antibiotics. VI. Conformation of 5-vinyl- and 5-ethynyl-2′-deoxyuridines

Abstract

PCILO computations have been carried out on the conformation of two potential antiviral nucleoside antibiotics, namely, 5-vinyl- and 5-ethynyl-2'-deoxyuridines, along with the parent nucleoside 5-methyl-2'-deoxyuridine (thymidine). The results indicate that the preferred conformation for all three molecules is syn (XCN = 240° for 5-vinyl- and 5-methyl-2'-deoxyuridine and 210°-240° for 5'-ethyl-2'-deoxyuridine) when an intramolecular hydrogen bonding possibility between the sugar and the base is allowed. The conformation around the exocyclic C(4')-C(5') bond is gt for the first two molecules, while for the third it is gg. However, in the absence of an intramolecular hydrogen bonding possibility, both nucleoside antibiotics as well as the parent nucleoside have strikingly similar preference for the anti-gg conformation. The biological implication of this similarity in terms of the mechanism of action of the two nucleoside antibiotics is discussed.