Anomeric effect in purine nucleosides. Evaluation of the steric effect of a purinic aglycon from the pseudorotational equilibrium of cyclopentane in carbocyclic C-nucleoside 1

A variable temperature 600 MHz H-1 NMR conformational analysis of (3)J(HH) coupling constants in pyrazolo[4,3-c]pyridine carbaribo-C-nucleoside 1 in D2O has shown that the carbocyclic nucleoside analogues in which the furanose ring is replaced by a cyclopentane are involved in a two-state N reversible arrow S (north reversible arrow south) pseudorotational equilibrium, which is in the case of 1 strongly biased toward an S-type conformation (P = 137 degrees, Psi(m) = 37 degrees, 90% at 298 K). The van't Hoff analysis of the population changes with temperature has shown that the pseudorotational equilibrium in 1 is driven toward S by a Delta H degrees of -11.6 kJ mol(-1). The two-state dynamic equilibrium is supported by ab initio calculations at HF, DFT, and MP2 levels which showed two energy wells in the N and S regions of conformational space. At the MP2/6-31(d) level the S-type conformer is preferred by 10.9 kJ mol(-1) over the local minimum in the N region of conformational space, which is in excellent agreement with our experimental value from the conformational analysis of (3)J(HH), The N and S energy minima are separated with the energy barrier of 24.0 kJ mol(-1) at the MP2 level, which suggests a rapid exchange on the NMR time scale between the interconverting conformers. The experimental quantitative estimate of Delta H(steric)degrees (-12.0 kJ mol(-1)) of the pyrazolopyridine moiety, which has been assumed to be isosteric with the purine moiety, has been used to calculate the energetic strengths of the O4'-Cl'-N9 anomeric effects of adenine and guanine in N-nucleosides: 16.4 kJ mol(-1) in ddA and ddG, 14.7 kJ mol(-1) in dA, 16.4 kJ mol(-1) in dG, 13.9 kJ mol(-1) in A, and 15.3 kJ mol(-1) in G.