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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/20/15091 |
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| author | Kindness L. Commey Akari Nakatake Airi Enaka Ryota Nakamura Koji Nishi Kenji Tsukigawa Hirohito Ikeda Koki Yamaguchi Daisuke Iohara Fumitoshi Hirayama Keishi Yamasaki Masaki Otagiri |
| author_facet | Kindness L. Commey Akari Nakatake Airi Enaka Ryota Nakamura Koji Nishi Kenji Tsukigawa Hirohito Ikeda Koki Yamaguchi Daisuke Iohara Fumitoshi Hirayama Keishi Yamasaki Masaki Otagiri |
| author_sort | Kindness L. Commey |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T21:12:30Z |
| format | Article |
| id | doaj.art-2859208fb89746b3823f4ef019660ac5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:12:30Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2859208fb89746b3823f4ef019660ac52023-11-19T16:41:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124201509110.3390/ijms242015091Study 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 DependencyKindness L. Commey0Akari Nakatake1Airi Enaka2Ryota Nakamura3Koji Nishi4Kenji Tsukigawa5Hirohito Ikeda6Koki Yamaguchi7Daisuke Iohara8Fumitoshi Hirayama9Keishi Yamasaki10Masaki Otagiri11Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Jonan-ku, Fukuoka 814-0180, JapanFaculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan4-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.https://www.mdpi.com/1422-0067/24/20/15091cyclodextrins4-phenylbutyrateinclusion complexationstructural chemistryinclusion modecavity size dependency |
| spellingShingle | Kindness L. Commey Akari Nakatake Airi Enaka Ryota Nakamura Koji Nishi Kenji Tsukigawa Hirohito Ikeda Koki Yamaguchi Daisuke Iohara Fumitoshi Hirayama Keishi Yamasaki Masaki Otagiri 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 International Journal of Molecular Sciences cyclodextrins 4-phenylbutyrate inclusion complexation structural chemistry inclusion mode 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 | cyclodextrins 4-phenylbutyrate inclusion complexation structural chemistry inclusion mode cavity size dependency |
| url | https://www.mdpi.com/1422-0067/24/20/15091 |
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