Acylated and alkylated benzo(crown-ethers) form ion-dependent ion channels in biological membranes

Synthetic ion channels based on benzo(crown-ether) compounds have been previously reported to function as ion-selective channels in planar lipid bilayers, with hydrogen bonding networks implicated in the formation of self-aggregated complexes. Herein, we report the synthesis and characterization of two new families of benzo(crown-ether) compounds, termed monoacylated and monoalkylated benzo(crown-ethers) (MABCE), both of which lack hydrogen bond donors. Depending on the length of alkyl chain substituent and the size of macrocycle, MABCE compounds inhibit bacterial growth and transport ions across biological membranes. Single-channel recordings show that the activity is higher in the presence of K thorn as compared with Na thorn ; however, under bionic conditions, open channels do not exhibit any preference between the two ions. These findings reveal that the ionic preference of benzo(crown-ether) compounds is either due to the regulation of assembly of ion-conducting supramolecular complexes or its membrane insertion by cations, as opposed to ion-selective transport through these scaffolds. Furthermore, our data show that the H-bonding network is not needed to form these assemblies in the membrane.

Automated summary

In this study, two new families of benzo(crown-ether) compounds, termed monoacylated and monoalkylated benzo(crown-ethers) (MABCE), were synthesized and characterized. These compounds can inhibit bacterial growth and transport ions across biological membranes. The results show that the preference of these compounds for specific ions is not achieved through ion-selective transport, but rather through the regulation of assembly of ion-conducting supramolecular complexes or its membrane insertion by cations. Additionally, the formation of these assemblies in the membrane does not require hydrogen bonding network.