title: Systematic investigation of DFT-GIAO15N NMR chemical shift prediction using B3LYP/cc-pVDZ: application to studies of regioisomers, tautomers, protonation states and N-oxides.
abstract: The calculation of15N 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 for15N 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 the15N 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 of15N prediction proved to be highly effective in identifying the correct regio-isomer, oxidation state, protonation state and preferred tautomer in solution.
authors.affiliation: Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA. nina.gonnella@boehringer-ingelheim.com.
authors.forename: Dongyue
authors.initials: D
authors.lastname: Xin
authors.affiliation: Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA. nina.gonnella@boehringer-ingelheim.com.
authors.forename: Charles Avery
authors.initials: CA
authors.lastname: Sader
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co.KG, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Fischer
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co.KG, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Wagner
authors.affiliation: Information Technology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA.
authors.forename: Paul-James
authors.initials: PJ
authors.lastname: Jones
authors.affiliation: Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA. nina.gonnella@boehringer-ingelheim.com.
authors.forename: Minli
authors.initials: M
authors.lastname: Xing
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fandrick
authors.affiliation: Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA. nina.gonnella@boehringer-ingelheim.com.
authors.forename: Nina C
authors.identifier: http://orcid.org/0000-0001-8944-7180
authors.initials: NC
authors.lastname: Gonnella
mesh_terms: D009682:Magnetic Resonance Spectroscopy / Q000592:standards; D009587:Nitrogen Isotopes; D010087:Oxides / Q000737:chemistry*; D011522:Protons; D011789:Quantum Theory; D012015:Reference Standards; D013237:Stereoisomerism
chemical_list: D009587:Nitrogen Isotopes; D010087:Oxides; D011522:Protons