Document Type: Article
Department of chemistry, Sharif University of Technology, Tehran, Iran P.O.Box 11365-9516
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 (H-H COSY, H-C HMQC and H-C HMBC) were analyzed. Optimized structures and spin-spin coupling constant calculations in gas and solution phases were performed by B3LYP/6-311++G(d,p) method. Both energy and NMR parameters showed that G1-form is more stable than other conformers. For coupling constant analysis, Karplus equations for 1JC-H, 2JC-H, and 3JC-Hwere derived. Also, solvent effect investigation performed and results showed both inter- and intra-molecular interactions affect stability of G1 conformer.