title: Ion channel formation from a calix[4]arene amide that binds HCl.
abstract: The ion transport activity of calix[4]arene tetrabutylamide 1,3-alt 2 was studied in liposomes, planar lipid bilayers, and HEK-293 cells. These experiments, when considered together with (1)H NMR and X-ray crystallography data, indicate that calix[4]arene tetrabutylamide 2 (1) forms ion channels in bilayer membranes, (2) mediates ion transport across cell membranes at positive holding potential, (3) alters the pH inside liposomes experiencing a Cl(-) gradient, and (4) shows a significant Cl(-)/SO(4)(2)(-) transport selectivity. An analogue, calix[4]arene tetramethylamide 1, self-assembles in the presence of HCl to generate solid-state structures with chloride-filled and water-filled channels. Structureminus signactivity studies indicate that the hydrophobicity, amide substitution, and macrocyclic framework of the calixarene are essential for HCl binding and transport. Calix[4]arene tetrabutylamide 2 is a rare example of an anion-dependent, synthetic ion channel.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sidorov
authors.forename: Frank W
authors.initials: FW
authors.lastname: Kotch
authors.forename: Galya
authors.initials: G
authors.lastname: Abdrakhmanova
authors.forename: Robert
authors.initials: R
authors.lastname: Mizani
authors.forename: James C
authors.initials: JC
authors.lastname: Fettinger
authors.forename: Jeffery T
authors.initials: JT
authors.lastname: Davis
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism; D047250:Calixarenes; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002712:Chlorides / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006851:Hydrochloric Acid / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008081:Liposomes; D008564:Membrane Potentials; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000737:chemistry* / Q000378:metabolism; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism
chemical_list: D000577:Amides; D002712:Chlorides; D007473:Ion Channels; D008051:Lipid Bilayers; D008081:Liposomes; D010636:Phenols; D013431:Sulfates; C121325:calix(4)arene; D047250:Calixarenes; D006851:Hydrochloric Acid