title: Development of a13C NMR Chemical Shift Prediction Procedure Using B3LYP/cc-pVDZ and Empirically Derived Systematic Error Correction Terms: A Computational Small Molecule Structure Elucidation Method.
abstract: An accurate and efficient procedure was developed for performing13C NMR chemical shift calculations employing density functional theory with the gauge invariant atomic orbitals (DFT-GIAO). Benchmarking analysis was carried out, incorporating several density functionals and basis sets commonly used for prediction of13C NMR chemical shifts, from which the B3LYP/cc-pVDZ level of theory was found to provide accurate results at low computational cost. Statistical analyses from a large data set of13C NMR chemical shifts in DMSO are presented with TMS as the calculated reference and with empirical scaling parameters obtained from a linear regression analysis. Systematic errors were observed locally for key functional groups and carbon types, and correction factors were determined. The application of this process and associated correction factors enabled assignment of the correct structures of therapeutically relevant compounds in cases where experimental data yielded inconclusive or ambiguous results. Overall, the use of B3LYP/cc-pVDZ with linear scaling and correction terms affords a powerful and efficient tool for structure elucidation.
authors.affiliation: Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.
authors.forename: Dongyue
authors.initials: D
authors.lastname: Xin
authors.affiliation: Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.|Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.
authors.forename: C Avery
authors.initials: CA
authors.lastname: Sader
authors.affiliation: Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.|Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.
authors.forename: Om
authors.initials: O
authors.lastname: Chaudhary
authors.affiliation: Information Technology, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.
authors.forename: Paul-James
authors.initials: PJ
authors.lastname: Jones
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co.KG , 88397 Biberach an der Riss, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Wagner
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co.KG , 88397 Biberach an der Riss, Germany.
authors.forename: Christofer S
authors.initials: CS
authors.lastname: Tautermann
authors.affiliation: Information Technology, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Busacca
authors.affiliation: Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.
authors.forename: Reginaldo A
authors.initials: RA
authors.lastname: Saraceno
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.
authors.forename: Keith R
authors.identifier: 0000-0003-4875-3143
authors.initials: KR
authors.lastname: Fandrick
authors.affiliation: Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.
authors.forename: Nina C
authors.initials: NC
authors.lastname: Gonnella
authors.affiliation: Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.
authors.forename: Keith
authors.initials: K
authors.lastname: Horspool
authors.forename: Gordon
authors.initials: G
authors.lastname: Hansen
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut 06877, United States.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Senanayake