Insights into molecular structure of adenosine-boron cluster conjugates and theirs phenyl isosters as adenosine receptor ligands: Nuclear magnetic resonance, crystallographic and computational studies

Detailed nuclear magnetic resonance (NMR), crystallographic and ab initio studies were performed on derivatives of adenosine and 2′-deoxyadenosine modified with boron clusters or alternatively with a phenyl group at position C8. The conformational study of these compounds showed very good agreement between the results established by these three methods. Substitution with a bulky substituent at C8 of adenosine strongly increased the population of the syn orientation around the glycosidic bond, accompanied by a predominance of the South-type conformation between C2’-endo-C3’-exo and C2’-endo-C1’-exo as well as the presence of the +sc orientation of the exocyclic C(4′)-C(5′) bond. Interestingly, 5′O–H····N3 scalar coupling across hydrogen bonds was observed in the 1H-15N gHMBC spectrum, indicating intramolecular 5′ O–H···N3 hydrogen bond formation as a consequence of the coexistence of the syn orientation, South-type conformation and +sc rotamer. The crystal structures of 5 and 7 are the first reported crystal structures of adenosine-boron cluster derivatives.