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 a computational quantum mechanical method (DFT) using Potential Energy Scanning (PES) in gas and solution phases in the Polarizable Continuum Model (PCM). Three stable conformers (G1, G2, and G3) were predicted from minimum points in a 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) was 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 01-form is more stable than other conformers are. To analyze coupling constant, Karplus equations for (1)J(C-H), (2)J(C-H), and (3)J(C-H) were derived. In addition, the investigation of solvent effect was carried out, and obtained results showed that both inter- and intra-molecular interactions affected the stability of G1 conformer. (C) 2018 Sharif University of Technology. All rights reserved.