Membrane activity of isophthalic acid derivatives:: Ion channel formation by a low molecular weight compound

A suite of 17 alkoxy-substituted isophthalic acid derivatives has been assessed for the ability to open well-defined ion channels in planar and vesicle bilayer membranes. One compound, 5-(12-tricosanoxy)-isophthalic acid, forms nonrectified cation selective channels with open lifetimes of the order of seconds and with mean specific conductance ranging from 9.2 pS for NaCl and 15.4 pS for KCl to 31.0 pS for CsCl. In addition to this dominant channel behavior, occasional variations in conductance levels suggest that related oligomeric channel structures can form. Channel formation is under close structural control as a compound bearing only two more methylene groups is significantly less active. The active compound has the lowest molecular weight of any known ion channel forming compound.