Conformational analysis of a cyclic nucleotide: 3′−5′‐Adenosine monophosphate. A study based on the extended Hückel theory

The extended Hückel theory (EHT) was used as a quantum mechanical approach for the determination of the best conformation of cyclic AMP. Both geometrical and quantum mechanical studies were necessary to ascertain the configuration of the sugar ring and phosphate ring. This was due to the fact that no crystallographic data are known for the ribose phosphate part of this nucleotide. The calculations have shown that the sugar ring takes a 3T4 (C3′‐endo–C4′‐exo) configuration while the phosphate ring exhibits a chair form. Once the geometry of the rigid ribose–phosphate block is resolved, the problem of the determination of the best conformation for cyclic AMP is reduced to the determination of the position of the adenine base with respect to this ribose phosphate part. The study of the rotation of the adenine base around the glycosidic bond C1′–N9 revealed that the two conformations anti (χ = 30°) and syn (ξ = 210°) are possible with an energy difference of only 1 kcal × mole−1. This theoretical calculation is in good agreement with experimental data.