Ion channel formation from a calix[4]arene amide that binds HCl.
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.
Sidorov
Vladimir
V
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, USA.
Kotch
Frank W
FW
Abdrakhmanova
Galya
G
Mizani
Robert
R
Fettinger
James C
JC
Davis
Jeffery T
JT
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
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