Researchers at the University of Brighton have investigated natural and synthetic transmembrane channel-forming molecules for the past two decades. This work suggested that it was possible to design compounds which would span a lipid bilayer and allow only one specific metal cation to pass through. The ability to control the passage of ions through a lipid – or cell – membrane has great therapeutic potential.
The project commenced in 2010 and ended in 2017.
A group of macrocyclic compounds together with their non-cyclic precursors was investigated using electrophysiological techniques with the aims of determining, if these compounds could allow cations to pass through a lipid bilayer and, if so, could they be modified to select only one cation in the manner observed for natural ion channel-forming protein-based molecules.
Sodium ion transport facilitated by a calixarene
Calixarene, oxacalixarene, pillararene and crown ether macrocycles were prepared from acyclic precursors. Their abilities to facilitate an ion flux were determined using two lipid mixtures for Na+ and K+. The most effective compound, a calixarene derivative, was tested with other cations and found to be Na+-selective in both lipid systems. Other macrocycles displayed a range of selectivities and the precursors were non-selective. The compounds were tested for antimicrobial and anticancer properties; some of the monomers were found to be bactericides.
Peter J Cragg
Pillararenes: fascinating cyclophanes with a bright future, PJ Cragg and K Sharma, Chem. Soc. Rev., 2012, 43, 597-607.