193 Biochimica et Biophysica Acta, 518 (1978) 193--204 © Elsevier/North-Holland Biomedical Press BBA 99145 MOLECULAR ORBITAL STUDIES ON NUCLEOSIDE ANALOGS II. CONFORMATION OF 6-AZAPYRIMIDINE NUCLEOSIDES CHANCHAL MITRA and ANIL SARAN Tara Institute of Fundamental Research, Homi Bhabha Road, Bombay 400005 (India) (Received August 16th, 1977) Summary PCILO (Perturbative Configuration Interaction using Localised Orbitals) com- putations have been carried out for three 6-azapyrimidine nucleosides, 6-aza- uridine, 6-azacytidine and 6-azathymidine, for both C(2')-endo and C(3')-endo pucker of the sugar ring. The results indicate a syn (×CN = 180°) conformation followed by ×CN = 90° and gg conformation for C(3')-endo 6-aza analogs as com- pared to the anti (×CN = 0 °) and gg conformation preferred by the correspond- ing pyrimidine nucleosides. For C(2')-endo sugar geometry, 6-azauridine and 6-azacytidine prefer, respectively, XCN = 0° (anti) and ¢c(4'~-c(5') = 60°C (gg) and ×CN = 2400 (syn) and ¢c(4')-c(5') = 120°. The corresponding nucleosides, uridine and cytidine, show a preference for syn (XCN= 240°) and gg and anti (XCN = 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-aza- uridine and 6-azacytidine in aqueous solutions are in agreement with the PCILO predictions. Introduction In a previous paper [1] the results of PCILO computations on the confor- mations of 8-azapurine nucleosides have been presented. Similar computa- tions have been extended here to predict the conformations of three 6-aza- pyrimidine nucleosides, 6-azauridine (6-aU), 6-azacytidine (6-aC) and 6-azathy- midine (6-aT). Both 6-aU and 6-aC are known to be carcinostatic agents [2--4] and a study of their conformational properties is of pharmacological interest. Besides, the present study also brings out the essential differences in the con- formations between the pyrimidine nucleosides and their 6-aza analogs. The schematic diagrams of 6-azauridine, 6-azacytidine and 6-azathymidine are presented in Fig. 1.