Membrane-active calixarenes: toward ‘gating’ transmembrane anion transport

This paper describes on-going efforts to develop calixarene amides as transmembrane anion transporters. We report on the transport of Cl⁻ anions across phospholipid membranes as mediated by some lipophilic calixarenes, all fixed in the cone conformation. We present significant findings regarding use of these calixarenes as transmembrane Cl⁻ transporters: (1) the cone conformer cone-H 2a, like its 1,3-alt and paco isomers, transports Cl⁻ across liposomal membranes; (2) the conformation of the calixarene (paco-H 1 vs cone-H 2a) is important for modulating Cl⁻ transport rates; (3) the substitution pattern on the calixarene's upper rim is crucial for Cl⁻ transport function; and (4) at least one of the four arms of the calixarene can be left unmodified without loss of function, enabling development of a pH-sensitive anion transporter (TAC-OH 3). This last finding is useful given the interest in gating the activity of synthetic ion transporters with external stimuli.