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Study of the Variation of the Electronic Distribution and Motional Dynamics of Two Independent Molecules of an Asymmetric Unit of Atorvastatin Calcium by Solid-State NMR Measurements

[Image: see text] Significant changes in the spin-lattice time and chemical shift anisotropy (CSA) parameters are observed in two independent molecules of an asymmetric unit of atorvastatin calcium (ATC-I) (which is referred to as “a”- and “b”-type molecules by following Wang et al.). The longitudin...

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Autores principales: Dey, Krishna Kishor, Lodhi, Lekhan, Ghosh, Manasi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427786/
https://www.ncbi.nlm.nih.gov/pubmed/34514246
http://dx.doi.org/10.1021/acsomega.1c03095
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author Dey, Krishna Kishor
Lodhi, Lekhan
Ghosh, Manasi
author_facet Dey, Krishna Kishor
Lodhi, Lekhan
Ghosh, Manasi
author_sort Dey, Krishna Kishor
collection PubMed
description [Image: see text] Significant changes in the spin-lattice time and chemical shift anisotropy (CSA) parameters are observed in two independent molecules of an asymmetric unit of atorvastatin calcium (ATC-I) (which is referred to as “a”- and “b”-type molecules by following Wang et al.). The longitudinal magnetization decay curve is fitted by two exponentials—one with longer relaxation time and another with shorter relaxation time for most of the carbon nuclei sites. The local correlation time also varies significantly. This is the experimental evidence of the coexistence of two different kinds of motional degrees of freedom within ATC-I molecule. The solubility and bioavailability of the drug molecule are enhanced due to the existence of two different kinds of dynamics. Hence, the macroscopic properties like solubility and bioavailability of a drug molecule are highly correlated with its microscopic properties. The motional degrees of freedom of “a”- and “b”-type molecules are also varied remarkably at certain carbon nuclei sites. This is the first time the change in the molecular dynamics of two independent molecules of an asymmetric unit of atorvastatin calcium is quantified using solid-state NMR methodology. These types of studies, in which the chemical shift anisotropy (CSA) parameters and spin-lattice relaxation time provide information about the change in electronic distribution and the spin dynamics at the various crystallographic location of the drug molecule, will enrich the field “NMR crystallography”. It will also help us to understand the electronic distribution around a nucleus and the nuclear spin dynamics at various parts of the molecule, which is essential to develop the strategies for the administration of the drug.
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spelling pubmed-84277862021-09-10 Study of the Variation of the Electronic Distribution and Motional Dynamics of Two Independent Molecules of an Asymmetric Unit of Atorvastatin Calcium by Solid-State NMR Measurements Dey, Krishna Kishor Lodhi, Lekhan Ghosh, Manasi ACS Omega [Image: see text] Significant changes in the spin-lattice time and chemical shift anisotropy (CSA) parameters are observed in two independent molecules of an asymmetric unit of atorvastatin calcium (ATC-I) (which is referred to as “a”- and “b”-type molecules by following Wang et al.). The longitudinal magnetization decay curve is fitted by two exponentials—one with longer relaxation time and another with shorter relaxation time for most of the carbon nuclei sites. The local correlation time also varies significantly. This is the experimental evidence of the coexistence of two different kinds of motional degrees of freedom within ATC-I molecule. The solubility and bioavailability of the drug molecule are enhanced due to the existence of two different kinds of dynamics. Hence, the macroscopic properties like solubility and bioavailability of a drug molecule are highly correlated with its microscopic properties. The motional degrees of freedom of “a”- and “b”-type molecules are also varied remarkably at certain carbon nuclei sites. This is the first time the change in the molecular dynamics of two independent molecules of an asymmetric unit of atorvastatin calcium is quantified using solid-state NMR methodology. These types of studies, in which the chemical shift anisotropy (CSA) parameters and spin-lattice relaxation time provide information about the change in electronic distribution and the spin dynamics at the various crystallographic location of the drug molecule, will enrich the field “NMR crystallography”. It will also help us to understand the electronic distribution around a nucleus and the nuclear spin dynamics at various parts of the molecule, which is essential to develop the strategies for the administration of the drug. American Chemical Society 2021-08-26 /pmc/articles/PMC8427786/ /pubmed/34514246 http://dx.doi.org/10.1021/acsomega.1c03095 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Dey, Krishna Kishor
Lodhi, Lekhan
Ghosh, Manasi
Study of the Variation of the Electronic Distribution and Motional Dynamics of Two Independent Molecules of an Asymmetric Unit of Atorvastatin Calcium by Solid-State NMR Measurements
title Study of the Variation of the Electronic Distribution and Motional Dynamics of Two Independent Molecules of an Asymmetric Unit of Atorvastatin Calcium by Solid-State NMR Measurements
title_full Study of the Variation of the Electronic Distribution and Motional Dynamics of Two Independent Molecules of an Asymmetric Unit of Atorvastatin Calcium by Solid-State NMR Measurements
title_fullStr Study of the Variation of the Electronic Distribution and Motional Dynamics of Two Independent Molecules of an Asymmetric Unit of Atorvastatin Calcium by Solid-State NMR Measurements
title_full_unstemmed Study of the Variation of the Electronic Distribution and Motional Dynamics of Two Independent Molecules of an Asymmetric Unit of Atorvastatin Calcium by Solid-State NMR Measurements
title_short Study of the Variation of the Electronic Distribution and Motional Dynamics of Two Independent Molecules of an Asymmetric Unit of Atorvastatin Calcium by Solid-State NMR Measurements
title_sort study of the variation of the electronic distribution and motional dynamics of two independent molecules of an asymmetric unit of atorvastatin calcium by solid-state nmr measurements
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427786/
https://www.ncbi.nlm.nih.gov/pubmed/34514246
http://dx.doi.org/10.1021/acsomega.1c03095
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