The conformations of 3′-azido-terminated-sulfonate-dimer 1 and 3′-amino-terminated-sulfonamide-dimer 2 are characterized by the following features: (1) The 5′-terminal nucleoside moiety of 1 has a S-type sugar (87% S), a staggered γ+ (rotamer across the C4′C5′ bond (65%) and an anti orientation of the base about the glycosidic bond. The 5′-terminal nucleoside moiety of 2 has an almost equal population of S and N conformations, a staggered γ+ rotamer (69 %) and an anti orientation of the base. (2) The 3′-terminal nucleoside moieties of 1 and 2 are in ∼50% N ⇄ S equilibrium and the γt conformer is the most populated. A comparison of the conformational properties of 1 and 2 with the natural thymidyl(3′ → 5′)thymidine [d(TpT)] 3, thymidylyl-(3′ → 5′)-5′-thio-5′-deoxythymide d(TpST)5 4 and thymidinylacetamido-[3′(O)→5′(C)]-5′-deoxythymidine NH2d(TcmT)5 5, show the following characteristics: (i) The conformational preference of the sugar ring is partially determined by the gauche effect. This means that the more polar the C3′X bond due to the electronegative character of the 3′-α-X substituent, the more than N ⇌ S equilibrium is biased toward the S-type conformation: 3′-O-S > 3′-O-H > 3′-N3 > 3′-NH2. (ii) The conformation about the C4′C5′ bond (γ) is also influenced by the gauche effect based on the nature of the 5′-substituent and by the ability of the 5′-substituent to form hydrogen bonding with the H6 of thymine. Thus, the population of the γ+ conformer follows the order: 5′-O > 5′-N > 5′-S > 5′-C. (iii) The C5′C6′ bond has a slight preference for the βt conformation (56 % βt in 1 and 58 % βt in 2), while in natural d(TpT) 3, the C5′O5′ bond accounts for 83% of βt conformation. Upon substitution of the 5′-oxygen by 5′-sulfur, as in d(TpST) 4, the population of βt conformer was found to decrease to 57 %. This decrease in the βt population in 1, 2 and 4 is a result of the reduced polarity of the 5′CX [X = CH2 in 1 and 2 and X S in 4] in comparaison to the 5′CO bond in 3, which weaken the gauche effect. © 1993.