Conformation of nucleosides: circular dichroism study on the syn-anti conformational equilibrium of 2-substituted benzimidazole nucleosides.

The solution conformations of 2-substituted derivatives of 1-(beta-D-ribofuranosyl)benzimidazole have been determined by circular dichroism spectroscopy in aqueous solutions. It is shown that analogs with methyl, amino, or methylamino substituents at position 2 of the benzimidazole ring (position 8 of the purine ring) have predominantly anti conformations, whereas analogs with chloro, aza, methoxy, or methylmercapto substituents have predominantly syn conformations. The preferred solution conformations of the benzimidazole nucleosides and analogous purine nucleosides are compared. The results demonstrate that the replacement of nitrogen by carbon at position 3 of the purine ring of purine (beta) nucleosides leads to important conformational consequences, which are strengthened or neutralized by substituents at position 8 of the purine ring.