The comparative analysis by NMR and ab initio calculations of the energetics of North ⇄ South pseudorotational equilibrium in 4\u27-thio-nucleosides and in their natural 4\u27-oxo counterparts has shown that S-C-N anomeric effect in the former is weaker than O-C-N anomeric effect in the latter. The ΔΔH° values between 2\u27-deoxy-4\u27-thio analogues and their 4\u27-oxo counterparts after accounting for the drive by 3\u27-OH group have been attributed to the weakening of the nucleobase-dependent S4\u27-C1\u27-N9/1 anomeric effect by 3.3, 6.5, 8.5 and 9.2 kJ mol-1 in adenine, guanine, cytosine and thymine, respectively. In addition, S-C-N anomeric effect is stronger in purine than in pyrimidine 4\u27-thionucleosides and increases in the following order: thymine < cytosine < guanine < adenine, which is in contrast to natural nucleosides
