1.D.103. The Synthetic Pillararene-based Unimolecular Tubular Channel (PUC) Family
Pillararenes are macrocycles that have rigid pillar backbones composed of hydroquinone units linked at the para postitions with methylene groups. This family of rigid molecular tubes provide frameworks for the construction of long tubular structures by the attachment of linear segments of tunable length.These have been used to make transmembrane channels by appending peptides onto the pillararene backbones (see Fig 1a in Chen et al. 2018). Hydrogen bonding among the adjacent peptides enhanced the stability of the tubular conformation in lipid bilayers. The length of the unimolecular pillararene channels with tripeptides can match the thickness of the lipid bilayers. The interaction between the channels and the bilayer can be modulated by alternating the sequences of the peptides or terminal groups. Appropriate modifications allow these channels to be bacterial-specific or mammalian cell-specific (Hurdle et al. 2011). The bacterium-specific channels seem to target phosphatidyl glycerol and other anionic lipids, serving as antibiotics that however are not prone to resistance. The mamalian channels may be specific for phosphatidyl choline and other zwitterionic lipid-containing membranes, and they insert into membranes with high efficiency (Chen et al. 2018). They have been shown to kill certain cancer cells.
A class of artificial K+ channels formed by pillararene-cyclodextrin hybrid molecules have been designed and synthesized (Xin et al. 2019). These channels efficiently insert into lipid bilayers and display high selectivity for K+ over Na+ in fluorescence and electrophysiological experiments. The cation transport selectivity of the artificial channels is tunable by varying the length of the linkers between pillararene and cyclodexrin. The shortest channel (1) showed specific transmembrane transport preferences for K+ in all alkali metal ions (selective sequence: K+ > Cs+ > Rb+ > Na+ >Li+), which is rarely observed in reported artificial K+ channels. The high selectivity for K+ over Na+ ensures specific transmembrane translocation of K+, which can generate a stable membrane potential across lipid bilayers (Xin et al. 2019).