Comparison of theoretical and experimental approaches to determination of conformation of nucleosides about the glycosidic bond.
A study has been made by means of 1H-NMR spectroscopy of the syn in equilibrium anti dynamic equilibrium about the glycosidic bond for 5'-deoxyadenosine and some 8-substituted analogues, in different solvents. The results are compared with those previously obtained for the parent adenosine and its 8-substituted analogues. Quantum chemical calculations, with the aid of the Classical Potential and PCILO procedures, were applied to obtain the energies for different conformations of the base in adenosine and 5'-deoxyadenosine, and their 8-methyl and 8-halogeno derivatives. Good agreement was found between experimentally determined conformations in solution and those corresponding theoretically to the energy minima, particularly those calculated by the PCILO method. Comparison of the quantitative experimental data with the theoretical results was used to evaluate the validity of the latter and their applicability to studies of nucleoside conformation. The experimental and theoretical findings pointed to the existence of a marked flexibility about the glycosidic bond of the parent nucleosides and their 8-substituted analogues, when the 8-substituents were not too bulky, such as methyl or bromine. Considerations is given to possible correlations between conformational parameters in nucleosides and their 5'-deoxy analogues. It is shown that the proposed stabilization of the conformation syn by intramolecular hydrogen bonding, 5'-OH...N(3), is not in accord with the results of the present study.
D000241:Adenosine / Q000031:analogs & derivatives*; D003839:Deoxyadenosines / Q000031:analogs & derivatives*; D006027:Glycosides; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D003839:Deoxyadenosines; D006027:Glycosides; D000241:Adenosine