title: Recognition and sequestration of ω-fatty acids by a cavitand receptor.
abstract: One of the largest driving forces for molecular association in aqueous solution is the hydrophobic effect, and many synthetic receptors with hydrophobic interiors have been devised for molecular recognition studies in water. Attempts to create the longer, narrower cavities appropriate for long-chain fatty acids have been thwarted by solvophobic collapse of the synthetic receptors, giving structures that have no internal spaces. The collapse generally involves the stacking of aromatic panels onto themselves. We describe here the synthesis and application of a deep cavitand receptor featuring "prestacked" aromatic panels at the upper rim of the binding pocket. The cavitand remains open and readily sequesters biologically relevant long-chain molecules-unsaturated ω-3, -6, and -9 fatty acids and derivatives such as anandamide-from aqueous media. The cavitand exists in isomeric forms with different stacking geometries and n-alkanes were used to characterize the binding modes and conformational properties. Long alkyl chains are accommodated in inverted J-shaped conformations. An analogous cavitand with electron-rich aromatic walls was prepared and comparative binding experiments indicated the role of intramolecular stacking in the binding properties of these deep container molecules.
authors: Department of Chemistry, Fudan University, Shanghai 200433, China; The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037; Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milano, Italy.
authors: Simone
authors: S
authors: Mosca
authors: The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037;
authors: Dariush
authors: D
authors: Ajami
authors: Department of Chemistry, Fudan University, Shanghai 200433, China; The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037; jrebek@scripps.edu.
authors: Julius
authors: J
authors: Rebek
mesh_terms: D001665:Binding Sites; D004988:Ethers, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000737:chemistry / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding; D012118:Resorcinols / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D004988:Ethers, Cyclic; D050556:Fatty Acid-Binding Proteins; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D012118:Resorcinols; C442939:cavitand
keywords: deep cavitands; fatty acids; molecular recognition; synthetic receptors; water-soluble cavitands