13C NMR can be a useful tool to determine the structure of unknown compounds, but it can be difficult to ascertain the correct assignment especially when the peaks of chemically similar sites overlap in the spectra. Molecular modeling and its relative theories such as Density Functional Theory (DFT) have advanced further in recent years and can be used to combat this ambiguity of NMR spectral assignment. DFT, the method employed here with the Castep module of Materials Studio software, can accurately refine crystal structures and predict NMR properties. The chemical of our group’s interest was cimetidine, a pharmaceutical polymorph with a well-researched X-ray diffraction pattern for its form A. Six different functionals with a plane-wave basis set were examined with dispersion interactions accounted for by using the Grimme D2* method. The damping parameter of D2* was also varied. The NMR parameters were calculated using the Gauge Included Plane Augmented Wave method. The agreement between experimental and predicted 13C chemical shift anisotropy values were used to assess the models. The Perdue-Wang 91 functional with dispersion corrections was found to be the best for optimizing the X-ray structure, outperforming other functionals with a rmsd of 3.2 ppm for the carbon peak assignment. Our solution to the 13C spectral assignment disagrees with the spectral assignment previously reported in the literature.

Predicting NMR chemical shift anisotropy of cimetidine with dispersion corrected plane-wave DFT

2019 Spring National Meeting

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