Conformational Flexibility of Pyrimidine Ring in Nucleic Acid Bases

Abstract

Nucleic acid bases (NABs) have been considered for many years to be planar and conformationally rigid. However, recently, two possible sources of nucleobases nonplanarity have been found. Ab initio quantum-chemical calculations using large basis sets augmented by inclusion of electron correlation and recent experimental studies revealed that amino groups in isolated cytosine, guanine, and adenine adopt a nonplanar trigonal-pyramidal configuration. Since the values of amino group inversion barriers do not exceed approximately 1 kcal mol−1, this group possesses rather flexible geometry. A different source of nonplanarity of nucleobases originates from the high deformability of the pyrimidine ring. Transition of such a ring in uracil, thymine, cytosine, and guanine molecules from a planar equilibrium conformation to a sofa configuration characterized by a relevant torsion angle of ±20° entails an increase of energy by less than 1.5 kcal mol−1. Therefore, at room temperature, certain fraction of isolated DNA bases should possess nonplanar structure of the heterocyclic ring. This review summarizes recent theoretical studies on the flexibility of the NABs.