A study of Li+-selective permeation through lipid bilayer membranes mediated by a new ionophore (AS701)

The neutral, noncyclic, imide and ether containing ionophore AS701, has been developed as Li+-selective molecule, to be used potentially as an aid in the Li+-therapy of manic-depressive illness. The present report is a characterization of this molecule in neutral lipid bilayer membranes. This ionophore was found to render the bilayers Li+-selective, acting as a selective carrier of monovalent cations. In addition, this molecule was found to be capable of acting as a selective carrier of monovalent anions. For both types of ions, the rate-limiting step in the process of permeation was found to be the diffusion of the carrier-ion complex through the membrane. The membrane-permeating species were found to be 2 : 1 carrier-ion complexes, carrying either a monovalent cation or a monovalent anion. The selectivity sequence among the ions studied being: Li+(1) greater than ClO4-(0.7) greater than Na+(0.07) greater than K+(0.016) greater than Rb+(0.0095) greater than Cs+(0.0083) greater than Cl-(0.001). Mg2+ and SO42- were found to be impermeant (under present experimental conditions). This sequence shows that the AS701 molecule has low selectivity for ions present in biological media, among those studied (i.e. Na+, K+, Mg2+, Cl- and SO42-). This indicates that these ions will not interfere in the Li+ permeability induced by this carrier in vivo, and that the carrier will not interfere in the normal transport processes of these ions.