Systematic investigation of DFT-GIAO N NMR chemical shift prediction using B3LYP/cc-pVDZ: application to studies of regioisomers, tautomers, protonation states and N-oxides.

The calculation of N NMR chemical shifts has been systematically investigated using density functional theory-gauge including/invariant atomic orbitals (DFT-GIAO) approximation at the B3LYP/cc-pVDZ level of theory. General linear regression terms for N chemical shift predictions were calculated for nitromethane and liquid ammonia references in DMSO. Both aliphatic and aromatic nitrogens were studied using a diverse set of molecular scaffolds. Statistical error analysis between experiment and prediction revealed that, with the exception of primary amines, 95% of linear scaled N-15 chemical shifts are within a ±9.56 ppm range. Comparison of the N calculated isotropic chemical shifts with the experimentally determined chemical shifts provided accurate assignment of the correct structure in cases where experimental data was ambiguous or inconclusive. Application of N prediction proved to be highly effective in identifying the correct regio-isomer, oxidation state, protonation state and preferred tautomer in solution.