Configurational effects on conformational properties of cyclic nucleotides. I. Theoretical calculations of conformer preferences in α‐nucleoside 3′,5′ cyclic monophosphates

Abstract

AbstractA comparative study has been made of the configurational effects on the conformational properties of α‐ and β‐anomers of purine and pyrimidine nucleoside 3′,5′,‐cyclic monophosphates and their 2′‐arabino epimers. Correlation between orientation of the base and the 2′‐hydroxyl group have been studied theoretically using the PCILO (Perturbative Configuration Interaction using Localized Orbitals) method. The effect of change in ribose puckering on the base‐hydroxyl interaction has also been studied. The result show that steric repulsions and stabilizing effects of intramolecular hydrogen bonding between the base and the 2′‐hydroxyl (OH) group are of major importance in determining configurations of α‐anomers and 2′‐arabino‐β‐epimers. For example, hydrogen bonding between the 2′‐hydroxyl group and polar centers on the base ring is clearly implicated as a determinant of syn‐anti preferences of the purine (adenine) or pyrimidine (uracil) bases in α‐nucleoside 3′,5′‐cyclic monophosphates. Moreover, barrier heights for interconversion between conformers are sensitive to ribose pucker and 2′‐OH orientations. The result clearly show that a change in ribose‐ring pucker plays an essential role in relieving repulsive interaction between the base and the 2′‐hydroxyl group. Thus a C2′‐exo‐C3′‐endo (2T3) pucker is favored for α‐anomers in contrast with the C4′‐exo‐C3′‐endo (4T3) from found in β‐compounds.