conformation of gemcitabine: an experimental nmr and theoretical dft study

The structural and conformational behavior of gemcitabine (2’, 2’-difluoro cytidine) was investigated by advanced nmr experiments and computational quantum mechanical method (dft) using potential energy scanning (pes) in gas and solution phases at polarizable continuum model (pcm). three stable conformers (g1, g2 and g3) were predicted from minimum points in potential energy diagram. in order to measure coupling constant values, a set of 2d spectra (hh cosy, hc hmqc and hc hmbc) were analyzed. optimized structures and spinspin coupling constant calculations in gas and solution phases were performed by b3lyp/6311++g(d,p) method. both energy and nmr parameters showed that g1form is more stable than other conformers. for coupling constant analysis, karplus equations for 1jch, 2jch, and 3jchwere derived. also, solvent effect investigation performed and results showed both inter and intramolecular interactions affect stability of g1 conformer.