Molecular orbital studies on nucleoside analogs II. Conformation of 6-azapyrimidine nucleosides

Abstract

PCILO (Perturbative Configuration Interaction using Localised Orbitals) computations have been carried out for three 6-azapyrimidine nucleosides, 6-azauridine, 6-azacytidine and 6-azathymidine, for both C(2′)-endo and C(3′)-endo pucker of the sugar ring. The results indicate a syn ( χ CN = 180°) conformation followed by χ CN = 90° and gg conformation for C(3′)-endo 6-aza analogs as compared to the anti ( χ CN = 0°) and gg conformation preferred by the corresponding pyrimidine nucleosides. For C(2′)-endo sugar geometry, 6-azauridine and 6-azacytidine prefer, respectively, χ CN = 0° ( anti) and Ф C(4′)- C(5′) = 60° C ( gg) and χ CN = 240° ( syn) and Ф C(4′)- C(5′) = 120° . The corresponding nucleosides, uridine and cytidine, show a preference for syn ( χ CN = 240°) and gg and anti ( χ CN = 0°) and gg, respectively. The X-ray crystallographic conformations of 6-azauridine and 6-azacytidine have been attributed to intermolecular hydrogen bonding and crystal packing forces. The results of PMR, CD and ORD studies on 6-azauridine and 6-azacytidine in aqueous solutions are in agreement with the PCILO predictions.