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Enhanced NMR Discrimination of Pharmaceutically Relevant Molecular Crystal Forms through Fragment-Based Ab Initio Chemical Shift Predictions
[Image: see text] Chemical shift prediction plays an important role in the determination or validation of crystal structures with solid-state nuclear magnetic resonance (NMR) spectroscopy. One of the fundamental theoretical challenges lies in discriminating variations in chemical shifts resulting fr...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095663/ https://www.ncbi.nlm.nih.gov/pubmed/27829821 http://dx.doi.org/10.1021/acs.cgd.6b01157 |
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author | Hartman, Joshua D. Day, Graeme M. Beran, Gregory J. O. |
author_facet | Hartman, Joshua D. Day, Graeme M. Beran, Gregory J. O. |
author_sort | Hartman, Joshua D. |
collection | PubMed |
description | [Image: see text] Chemical shift prediction plays an important role in the determination or validation of crystal structures with solid-state nuclear magnetic resonance (NMR) spectroscopy. One of the fundamental theoretical challenges lies in discriminating variations in chemical shifts resulting from different crystallographic environments. Fragment-based electronic structure methods provide an alternative to the widely used plane wave gauge-including projector augmented wave (GIPAW) density functional technique for chemical shift prediction. Fragment methods allow hybrid density functionals to be employed routinely in chemical shift prediction, and we have recently demonstrated appreciable improvements in the accuracy of the predicted shifts when using the hybrid PBE0 functional instead of generalized gradient approximation (GGA) functionals like PBE. Here, we investigate the solid-state (13)C and (15)N NMR spectra for multiple crystal forms of acetaminophen, phenobarbital, and testosterone. We demonstrate that the use of the hybrid density functional instead of a GGA provides both higher accuracy in the chemical shifts and increased discrimination among the different crystallographic environments. Finally, these results also provide compelling evidence for the transferability of the linear regression parameters mapping predicted chemical shieldings to chemical shifts that were derived in an earlier study. |
format | Online Article Text |
id | pubmed-5095663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-50956632016-11-07 Enhanced NMR Discrimination of Pharmaceutically Relevant Molecular Crystal Forms through Fragment-Based Ab Initio Chemical Shift Predictions Hartman, Joshua D. Day, Graeme M. Beran, Gregory J. O. Cryst Growth Des [Image: see text] Chemical shift prediction plays an important role in the determination or validation of crystal structures with solid-state nuclear magnetic resonance (NMR) spectroscopy. One of the fundamental theoretical challenges lies in discriminating variations in chemical shifts resulting from different crystallographic environments. Fragment-based electronic structure methods provide an alternative to the widely used plane wave gauge-including projector augmented wave (GIPAW) density functional technique for chemical shift prediction. Fragment methods allow hybrid density functionals to be employed routinely in chemical shift prediction, and we have recently demonstrated appreciable improvements in the accuracy of the predicted shifts when using the hybrid PBE0 functional instead of generalized gradient approximation (GGA) functionals like PBE. Here, we investigate the solid-state (13)C and (15)N NMR spectra for multiple crystal forms of acetaminophen, phenobarbital, and testosterone. We demonstrate that the use of the hybrid density functional instead of a GGA provides both higher accuracy in the chemical shifts and increased discrimination among the different crystallographic environments. Finally, these results also provide compelling evidence for the transferability of the linear regression parameters mapping predicted chemical shieldings to chemical shifts that were derived in an earlier study. American Chemical Society 2016-10-04 2016-11-02 /pmc/articles/PMC5095663/ /pubmed/27829821 http://dx.doi.org/10.1021/acs.cgd.6b01157 Text en Copyright © 2016 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
spellingShingle | Hartman, Joshua D. Day, Graeme M. Beran, Gregory J. O. Enhanced NMR Discrimination of Pharmaceutically Relevant Molecular Crystal Forms through Fragment-Based Ab Initio Chemical Shift Predictions |
title | Enhanced NMR Discrimination of Pharmaceutically Relevant
Molecular Crystal Forms through Fragment-Based Ab Initio Chemical
Shift Predictions |
title_full | Enhanced NMR Discrimination of Pharmaceutically Relevant
Molecular Crystal Forms through Fragment-Based Ab Initio Chemical
Shift Predictions |
title_fullStr | Enhanced NMR Discrimination of Pharmaceutically Relevant
Molecular Crystal Forms through Fragment-Based Ab Initio Chemical
Shift Predictions |
title_full_unstemmed | Enhanced NMR Discrimination of Pharmaceutically Relevant
Molecular Crystal Forms through Fragment-Based Ab Initio Chemical
Shift Predictions |
title_short | Enhanced NMR Discrimination of Pharmaceutically Relevant
Molecular Crystal Forms through Fragment-Based Ab Initio Chemical
Shift Predictions |
title_sort | enhanced nmr discrimination of pharmaceutically relevant
molecular crystal forms through fragment-based ab initio chemical
shift predictions |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095663/ https://www.ncbi.nlm.nih.gov/pubmed/27829821 http://dx.doi.org/10.1021/acs.cgd.6b01157 |
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