Interfacial properties of most monofluorinated bile acids deviate markedly from the natural congeners
We characterized the air-water interfacial properties of four monofluorinated bile acids alone and in binary mixtures with a common lecithin, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), using an automated Langmuir-Pockels surface balance. We compared 7α-fluoromurocholic acid (FMCA), 7α-...
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| Format: | Article |
| Language: | English |
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Elsevier
2005-03-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520340414 |
| _version_ | 1818728302587674624 |
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| author | John M. Kauffman Roberto Pellicciari Martin C. Carey |
| author_facet | John M. Kauffman Roberto Pellicciari Martin C. Carey |
| author_sort | John M. Kauffman |
| collection | DOAJ |
| description | We characterized the air-water interfacial properties of four monofluorinated bile acids alone and in binary mixtures with a common lecithin, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), using an automated Langmuir-Pockels surface balance. We compared 7α-fluoromurocholic acid (FMCA), 7α-fluorohyodeoxycholic acid (FHDCA), 6α-fluoroursodeoxycholic acid (FUDCA), and 6α-fluorochenodeoxycholic acid (FCDCA) with their natural dihydroxy homologs, murocholic acid (MCA), hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA). For further comparison, two trihydroxy bile acids, 3α,6β,7α-trihydroxycholanoic acid [α-muricholic acid (α-MCA)] and 3α,6α,7β-trihydroxycholanoic acid [ω-muricholic acid (ω-MCA)], with isologous OH polar functions to FMCA and FUDCA were also studied. Pressure-area isotherms of MCA, HDCA, UDCA, CDCA, and FMCA displayed sharp collapse points. In contrast, FHDCA, FUDCA, and FCDCA formed monolayers that were less stable than the trihydroxy bile acids, displaying second-order phase transitions in their isotherms. All natural and fluorinated bile acids condensed mixed monolayers with POPC, with maximal effects at molar bile acid concentrations between 30 and 50 mol%. Examination of molecular models revealed that the 7α-F atom of the interfacially stable FMCA projects away from the 6β-OH function, resulting in minimal steric interactions, whereas in FHDCA, FUDCA, and FCDCA, close vicinal interactions between OH and F polar functions result in progressive bulk solubility upon monolayer compression.These results provide a framework for designing F-modified bile acids to mimic or diverge from the natural compounds in vivo. |
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| id | doaj.art-97eab2897a0944c6b6df3b55120464bd |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T22:27:50Z |
| publishDate | 2005-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-97eab2897a0944c6b6df3b55120464bd2022-12-21T21:30:19ZengElsevierJournal of Lipid Research0022-22752005-03-01463571581Interfacial properties of most monofluorinated bile acids deviate markedly from the natural congenersJohn M. Kauffman0Roberto Pellicciari1Martin C. Carey2Department of Medicine, Harvard Medical School, Harvard Digestive Diseases Center, and Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA; Dipartimento di Chimica é Tecnologia del Farmaco, Università di Perugia, Perugia, ItalyDepartment of Medicine, Harvard Medical School, Harvard Digestive Diseases Center, and Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA; Dipartimento di Chimica é Tecnologia del Farmaco, Università di Perugia, Perugia, ItalyDepartment of Medicine, Harvard Medical School, Harvard Digestive Diseases Center, and Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA; Dipartimento di Chimica é Tecnologia del Farmaco, Università di Perugia, Perugia, ItalyWe characterized the air-water interfacial properties of four monofluorinated bile acids alone and in binary mixtures with a common lecithin, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), using an automated Langmuir-Pockels surface balance. We compared 7α-fluoromurocholic acid (FMCA), 7α-fluorohyodeoxycholic acid (FHDCA), 6α-fluoroursodeoxycholic acid (FUDCA), and 6α-fluorochenodeoxycholic acid (FCDCA) with their natural dihydroxy homologs, murocholic acid (MCA), hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA). For further comparison, two trihydroxy bile acids, 3α,6β,7α-trihydroxycholanoic acid [α-muricholic acid (α-MCA)] and 3α,6α,7β-trihydroxycholanoic acid [ω-muricholic acid (ω-MCA)], with isologous OH polar functions to FMCA and FUDCA were also studied. Pressure-area isotherms of MCA, HDCA, UDCA, CDCA, and FMCA displayed sharp collapse points. In contrast, FHDCA, FUDCA, and FCDCA formed monolayers that were less stable than the trihydroxy bile acids, displaying second-order phase transitions in their isotherms. All natural and fluorinated bile acids condensed mixed monolayers with POPC, with maximal effects at molar bile acid concentrations between 30 and 50 mol%. Examination of molecular models revealed that the 7α-F atom of the interfacially stable FMCA projects away from the 6β-OH function, resulting in minimal steric interactions, whereas in FHDCA, FUDCA, and FCDCA, close vicinal interactions between OH and F polar functions result in progressive bulk solubility upon monolayer compression.These results provide a framework for designing F-modified bile acids to mimic or diverge from the natural compounds in vivo.http://www.sciencedirect.com/science/article/pii/S0022227520340414phosphatidylcholinecondensationpressure-area isothermorientationbulk solubilityfarnesoid X receptor |
| spellingShingle | John M. Kauffman Roberto Pellicciari Martin C. Carey Interfacial properties of most monofluorinated bile acids deviate markedly from the natural congeners Journal of Lipid Research phosphatidylcholine condensation pressure-area isotherm orientation bulk solubility farnesoid X receptor |
| title | Interfacial properties of most monofluorinated bile acids deviate markedly from the natural congeners |
| title_full | Interfacial properties of most monofluorinated bile acids deviate markedly from the natural congeners |
| title_fullStr | Interfacial properties of most monofluorinated bile acids deviate markedly from the natural congeners |
| title_full_unstemmed | Interfacial properties of most monofluorinated bile acids deviate markedly from the natural congeners |
| title_short | Interfacial properties of most monofluorinated bile acids deviate markedly from the natural congeners |
| title_sort | interfacial properties of most monofluorinated bile acids deviate markedly from the natural congeners |
| topic | phosphatidylcholine condensation pressure-area isotherm orientation bulk solubility farnesoid X receptor |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520340414 |
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