New Li+-selective ionophores with the potential ability to mediate Li+-transport in vivo

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Abstract
A series of structurally-related Li+-selective ionophores were studied in planar lipid bilayer membranes, to assess their potential ability to act as Li+-selective carriers in vivo. The ionophores are acyclic, neutral molecules of similar structure: N,N′-diheptyl-N,N′-diR-5,5-dimethyl-3,7-dioxanonane diamide. The structural differences among them are the N-amide substituents (the R residues) as follows: an aliphatic ether (AS 701), tetrahydrofuran (AS 706), furan (AS 708), an ester (AS 702) and an amide (AS 704) For each ionophore, the steady-state, single salt, membrane conductances and conductance-voltage behaviors were determined in the presence of LiCl, NaCl and MgCl2. Membrane zero-current potentials were measurd for NaCl/LiCl and MgCl2/LiCl mixtures. All five ionophores were found to operate as “equilibrium-domain” carriers of monovalent ions. All select lithium over sodium, but with different magnitudes of selectivity, ranging from PLi/PNa of 13 (for AS 701) to PLi/PNa of 2 (for AS 708). The ionophores also differ in their ability to mediate Li+ membrane permeation, the order of decreasing potency being: AS 701≧AS 706>AS 702>AS 704≧AS 708. Of the five molecules studied, the AS 701 molecule was found to have the best Li+ over Na+ selectivity and highest potency. These findings indicate that this molecule has the best potential for mediating lithium-selective membrane permeation in vivo, among the group studied.

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