Conformation of adenosine 5′‐phosphate in solution, deduced from experimental and simulated proton T₁ values

A computer program developed for the simulation of proton spin‐lattice relaxation times ( T 1 ) was applied to the conformational analysis of adenosine 5′‐phosphate (5′‐AMP) in neutral D 2 O solution. The T 1 values of all the non‐exchangeable protons of 5′‐AMP were calculated from the atomic coordinates of the hydrogens and the rotational correlation times by numerically solving a simultaneous differential equation for all the proton magnetizations of the molecule. However, no single conformation gave a good enough agreement between the calculated and observed T 1 values. 5′‐AMP in solution must therefore be in conformational equilibrium. The equilibrium around the C‐4′–C‐5′ bond was fixed as gauche ‐ trans (16%), gauche ‐ gauche (68%) and trans ‐ gauche (16%) from the spin coupling constant. A correlation was found to exist between two conformational equilibria, anti ⇌ syn and 2′‐ endo ⇌ 3′‐ endo . The best agreement between the calculated and observed T 1 values was obtained for an equilibrium between three conformers, 2′‐ endo ‐ anti (Z = 60°) 40–53%, 3′‐ endo ‐ anti (Z = 30°) 18–28% and 2′‐ endo ‐ syn (Z = 220–260°) 27–30%. This equilibrium was consistent with all the currently available information about the conformation of 5′‐AMP in solution. 5′‐AMP exists only in the anti conformation in the crystal. This is similar to our results that the anti is the major conformation at 58–81%, but the syn conformer also exists as 19–42% in solution.