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Study of the Structural Chemistry of the Inclusion Complexation of 4-Phenylbutyrate and Related Compounds with Cyclodextrins in Solution: Differences in Inclusion Mode with Cavity Size Dependency
4-phenylbutyrate (PB) and structurally related compounds hold promise for treating many diseases, including cancers. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their evaluation and clinical use. This study explores cyclodextrin (CD) complexati...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606765/ https://www.ncbi.nlm.nih.gov/pubmed/37894771 http://dx.doi.org/10.3390/ijms242015091 |
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author | Commey, Kindness L. Nakatake, Akari Enaka, Airi Nakamura, Ryota Nishi, Koji Tsukigawa, Kenji Ikeda, Hirohito Yamaguchi, Koki Iohara, Daisuke Hirayama, Fumitoshi Yamasaki, Keishi Otagiri, Masaki |
author_facet | Commey, Kindness L. Nakatake, Akari Enaka, Airi Nakamura, Ryota Nishi, Koji Tsukigawa, Kenji Ikeda, Hirohito Yamaguchi, Koki Iohara, Daisuke Hirayama, Fumitoshi Yamasaki, Keishi Otagiri, Masaki |
author_sort | Commey, Kindness L. |
collection | PubMed |
description | 4-phenylbutyrate (PB) and structurally related compounds hold promise for treating many diseases, including cancers. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their evaluation and clinical use. This study explores cyclodextrin (CD) complexation as a strategy to address these limitations. The structural chemistry of the CD complexes of these compounds was analyzed using phase solubility, nuclear magnetic resonance (NMR) spectroscopic techniques, and molecular modeling to inform the choice of CD for such application. The study revealed that PB and its shorter-chain derivative form 1:1 αCD complexes, while the longer-chain derivatives form 1:2 (guest:host) complexes. αCD includes the alkyl chain of the shorter-chain compounds, depositing the phenyl ring around its secondary rim, whereas two αCD molecules sandwich the phenyl ring in a secondary-to-secondary rim orientation for the longer-chain derivatives. βCD includes each compound to form 1:1 complexes, with their alkyl chains bent to varying degrees within the CD cavity. γCD includes two molecules of each compound to form 2:1 complexes, with both parallel and antiparallel orientations plausible. The study found that αCD is more suitable for overcoming the pharmaceutical drawbacks of PB and its shorter-chain derivative, while βCD is better for the longer-chain derivatives. |
format | Online Article Text |
id | pubmed-10606765 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106067652023-10-28 Study of the Structural Chemistry of the Inclusion Complexation of 4-Phenylbutyrate and Related Compounds with Cyclodextrins in Solution: Differences in Inclusion Mode with Cavity Size Dependency Commey, Kindness L. Nakatake, Akari Enaka, Airi Nakamura, Ryota Nishi, Koji Tsukigawa, Kenji Ikeda, Hirohito Yamaguchi, Koki Iohara, Daisuke Hirayama, Fumitoshi Yamasaki, Keishi Otagiri, Masaki Int J Mol Sci Article 4-phenylbutyrate (PB) and structurally related compounds hold promise for treating many diseases, including cancers. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their evaluation and clinical use. This study explores cyclodextrin (CD) complexation as a strategy to address these limitations. The structural chemistry of the CD complexes of these compounds was analyzed using phase solubility, nuclear magnetic resonance (NMR) spectroscopic techniques, and molecular modeling to inform the choice of CD for such application. The study revealed that PB and its shorter-chain derivative form 1:1 αCD complexes, while the longer-chain derivatives form 1:2 (guest:host) complexes. αCD includes the alkyl chain of the shorter-chain compounds, depositing the phenyl ring around its secondary rim, whereas two αCD molecules sandwich the phenyl ring in a secondary-to-secondary rim orientation for the longer-chain derivatives. βCD includes each compound to form 1:1 complexes, with their alkyl chains bent to varying degrees within the CD cavity. γCD includes two molecules of each compound to form 2:1 complexes, with both parallel and antiparallel orientations plausible. The study found that αCD is more suitable for overcoming the pharmaceutical drawbacks of PB and its shorter-chain derivative, while βCD is better for the longer-chain derivatives. MDPI 2023-10-11 /pmc/articles/PMC10606765/ /pubmed/37894771 http://dx.doi.org/10.3390/ijms242015091 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Commey, Kindness L. Nakatake, Akari Enaka, Airi Nakamura, Ryota Nishi, Koji Tsukigawa, Kenji Ikeda, Hirohito Yamaguchi, Koki Iohara, Daisuke Hirayama, Fumitoshi Yamasaki, Keishi Otagiri, Masaki Study of the Structural Chemistry of the Inclusion Complexation of 4-Phenylbutyrate and Related Compounds with Cyclodextrins in Solution: Differences in Inclusion Mode with Cavity Size Dependency |
title | Study of the Structural Chemistry of the Inclusion Complexation of 4-Phenylbutyrate and Related Compounds with Cyclodextrins in Solution: Differences in Inclusion Mode with Cavity Size Dependency |
title_full | Study of the Structural Chemistry of the Inclusion Complexation of 4-Phenylbutyrate and Related Compounds with Cyclodextrins in Solution: Differences in Inclusion Mode with Cavity Size Dependency |
title_fullStr | Study of the Structural Chemistry of the Inclusion Complexation of 4-Phenylbutyrate and Related Compounds with Cyclodextrins in Solution: Differences in Inclusion Mode with Cavity Size Dependency |
title_full_unstemmed | Study of the Structural Chemistry of the Inclusion Complexation of 4-Phenylbutyrate and Related Compounds with Cyclodextrins in Solution: Differences in Inclusion Mode with Cavity Size Dependency |
title_short | Study of the Structural Chemistry of the Inclusion Complexation of 4-Phenylbutyrate and Related Compounds with Cyclodextrins in Solution: Differences in Inclusion Mode with Cavity Size Dependency |
title_sort | study of the structural chemistry of the inclusion complexation of 4-phenylbutyrate and related compounds with cyclodextrins in solution: differences in inclusion mode with cavity size dependency |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606765/ https://www.ncbi.nlm.nih.gov/pubmed/37894771 http://dx.doi.org/10.3390/ijms242015091 |
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