An atomic resolution description of folic acid using solid state NMR measurements

Ghosh, Manasi; Gayen, Shovanlal; Dey, Krishna Kishor

doi:10.1039/d0ra03772a

Cited by 16 publications

(25 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29−32 Wang et al 1 evaluated the CSA tensor by DFT calculations. We have measured principal components of the CSA tensor of 33 crystallographically different carbon nuclei of "a"and "b"-type molecules by 13 C 2DPASS CP-MAS SSNMR experiments. We have also observed two well-resolved resonance lines for certain carbon nuclei sites corresponding to two different molecules of the asymmetric unit as previously reported by Wang et al 1 Figure 1a,b shows the structure and 13 C CP-MAS SSNMR spectrum of ATC-I at a MAS frequency of 10 kHz, respectively.…”

Section: Resultssupporting

confidence: 86%

“…4,5 13 C 2DPASS CP-MAS SSNMR spectroscopy was used to find the principal components of CSA parameters of charge-transfer co-crystal, biopolymers, and drug molecules. 6−16 The molecular dynamics of "a" and "b" types of molecules (the types "a" and "b" nomenclature is according to Wang et al 1 ) is determined by measuring 13 C spin-lattice relaxation time by the Torchia CP method and by calculating the molecular correlation time at crystallographically different locations of carbon nuclei.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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

2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…37 2DPASS CP-MAS ( two-dimensional phase adjusted spinning sideband cross-polarization magic angle spinning) SSNMR experiment 38,39 was developed to separate anisotropic and isotropic chemical shift interactions under low magic angle spinning (MAS) frequency using sequences of five pulses. The correlation between the structure and dynamics of biopolymer and drugs molecules [40][41][42][43][44][45][46][47][48][49][50][51] were studied by measuring principal components of CSA parameters and site specific spin-lattice relaxation time by applying 2DPASS CP-MAS SSNMR experiments 38,39 and Torchia CP experiment 52 respectively. The main focus of the present work is to study the structure and dynamics of antifungal agent ketoconazole by the 2DPASS CP-MAS SSNMR experiments 38,39 and the Torchia CP experiments.…”

Section: Because Of This Property Ketoconazole Is Used For the Treatmentioning

confidence: 99%

Study the Structure and Dynamics of Antifungal Agent Ketoconazole by CSA and Site-Specific Spin-Lattice Relaxation Time Measurements

Dey¹,

Ghosh²

2021

Preprint

Self Cite

View full text Add to dashboard Cite

An azole antifungal agent, ketoconazole, is widely used in the treatment of mucosal fungal infections related to AIDS immunosuppression, organ transplantation, and cancer chemotherapy. The structure and dynamics of ketoconazole are thoroughly studied by chemical shift anisotropy tensor and site-specific spin-lattice relaxation time measurements. The molecular correlation time at crystallographically different carbon sites is calculated by considering that the spin-lattice relaxation mechanism for the 13C nucleus is mainly governed by chemical shift anisotropy interaction and hetero-nuclear dipole-dipole coupling. The CSA parameters at the crystallographically distinct sites of ketoconazole are determined by two-dimensional phase adjusted spinning sideband (2D PASS) cross-polarization magic angle spinning (CP-MAS) solid-state NMR experiment. The site-specific spin-lattice relaxation time is measured by the Torchia CP experiment. The spin-lattice relaxation rate is slow for all the carbon nuclei sites except C2, C3, C4, C5, and C26 carbon nuclei reside on the piperazine ring and the methyl group. It suggests the close-pack arrangement of the molecule due to π-π stacking interaction. The molecular correlation time of all the carbon atoms reside on the benzene ring, 1,3-dioxolane ring, imidazole ring, and the 2,4-dichlorobenzene ring is of the order of 10-4 s, while it is of the order of 10-7 s for carbon atoms reside on the piperazine ring. The CSA parameters of the carbon nuclei on the piperazine ring (C2, C3, C4, C5), and the methyl group (C26) are very low compared to other carbon nuclei. The CSA parameters are very high for carbon nuclei reside on the benzene ring, imidazole ring, and the 2,4-dichlorobenzene ring due to the presence of π-electrons. A huge variation of the spin-lattice relaxation time and the molecular correlation time are observed for numerous carbon nuclei situated on the side-chain of ketoconazole. The spin-lattice relaxation time varies from 500 s to 8 s, and the molecular correlation time varies in the range of 10-4s to 10-7s. These types of investigations portrayed the correlation between the structure and dynamics of the antifungal drug ketoconazole, which will help to develop the advanced antifungal drugs. Additionally, the CSA information of the drug molecules will be immensely useful for NMR crystallography.

show abstract

“…The applications of the 2DPASS CP‐MAS SSNMR experiment on the natural abundance of the 13 C nucleus do not get affected by the hetero‐nuclear and homo‐nuclear dipolar couplings. The correlation between the structure and dynamics of biopolymer, cocrystal, and drug molecules [40–51] was determined by measuring principal components of CSA parameters and site‐specific spin‐lattice relaxation time by applying 2DPASS CP‐MAS SSNMR experiments [38,39] and Torchia CP experiment [52] respectively. Holmes et al [53] .…”

Section: Introductionmentioning

confidence: 99%

A Description of the Local Structure and Dynamics of Ketoconazole Molecule by Solid‐State NMR Measurements and DFT Calculations: Proposition for NMR Crystallography

Dey

Deshmukh

Ghosh³

2021

ChemistrySelect

Self Cite

View full text Add to dashboard Cite

An azole class antifungal agent, ketoconazole, is widely used in the treatment of mucosal fungal infections that arise due to AIDS immunosuppression, organ transplantation, and cancer chemotherapy. The structure and dynamics of various molecular moieties of ketoconazole are thoroughly studied by measuring chemical shift anisotropy tensor and site‐specific spin‐lattice relaxation time. The local correlation time at crystallographically different carbon nuclei sites is also calculated. The chemical shift anisotropy (CSA) parameters at the crystallographically distinct sites of ketoconazole are determined by the two‐dimensional phase‐adjusted spinning sideband (2D PASS) cross‐polarization magic angle spinning (CP‐MAS) solid‐state NMR experiment. The site‐specific spin‐lattice relaxation time is measured by the method outlined by Torchia (T1CP). The values of the principal components of CSA parameters extracted by the 2DPASS CP‐MAS ssNMR experiment are supported by density functional theory (DFT) calculations. The CSA parameters are high for those carbon nuclei, whose spin‐lattice relaxation rate is slow, and it is low for those carbon nuclei whose spin‐lattice relaxation rate is fast. It suggests that the spin‐lattice relaxation mechanism is mainly governed by chemical‐shift anisotropy interaction for these carbon nuclei. A huge variation of the spin‐lattice relaxation time and the local correlation time are observed for numerous carbon nuclei that reside on the side‐chain of the molecule. The spin‐lattice relaxation time varies from 500 s to 8 s, and the order of the local correlation time varies from 10-4 s to 10-7 s. These types of studies in which the chemical shift anisotropy (CSA) parameters and spin‐lattice relaxation time provide information about the electronic configuration and the spin dynamics at the various crystallographic locations of the drug molecule will enrich the field “NMR crystallography.” It will also help to develop the strategies for the administration of antifungal drugs by providing information about the structure and dynamics of various parts of the drug molecule.

show abstract

An atomic resolution description of folic acid using solid state NMR measurements

Abstract:
The chemical shift anisotropy tensor and site specific spin-lattice relaxation time of folic acid were determined by a ¹³C 2DPASS CP-MAS NMR experiment and Torchia CP experiment respectively.

Cited by 16 publications

References 34 publications

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

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

Study the Structure and Dynamics of Antifungal Agent Ketoconazole by CSA and Site-Specific Spin-Lattice Relaxation Time Measurements

A Description of the Local Structure and Dynamics of Ketoconazole Molecule by Solid‐State NMR Measurements and DFT Calculations: Proposition for NMR Crystallography

Contact Info

Product

Resources

About

An atomic resolution description of folic acid using solid state NMR measurements

Abstract: The chemical shift anisotropy tensor and site specific spin-lattice relaxation time of folic acid were determined by a 13C 2DPASS CP-MAS NMR experiment and Torchia CP experiment respectively.

Cited by 16 publications

References 34 publications

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

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

Study the Structure and Dynamics of Antifungal Agent Ketoconazole by CSA and Site-Specific Spin-Lattice Relaxation Time Measurements

A Description of the Local Structure and Dynamics of Ketoconazole Molecule by Solid‐State NMR Measurements and DFT Calculations: Proposition for NMR Crystallography

Contact Info

Product

Resources

About

Abstract:
The chemical shift anisotropy tensor and site specific spin-lattice relaxation time of folic acid were determined by a ¹³C 2DPASS CP-MAS NMR experiment and Torchia CP experiment respectively.