Source: School of Chemistry
Written by: School of Chemistry
Edited by: Wang Dongmei

Recently foreign guest professor Mihail Barboiu and his PhD student Shaoping Zheng from Lehn Institute of Functional Materials, School of Chemistry, Sun Yat-sen University reported the first example of synergetic H-bonding/anion-π anion channel based on self-assembled columnar triazole-quartets. Their work was published as the back cover paper in scientific journal Angew. Chem. Int. Ed., also recognized as VIP (Very Important Paper, 5%).

Ion transmembrane translocation through protein channels is of great significance for regulating the cellular signalling pathways. A number of clinical diseases, arising from dysfunction of biological channels, known as “channelopathies” are related to defects observed in the protein structures. Synthetic ion-channels can replace them as a novel medical therapy, having great potential in anticancer treatment.

In protein channels, the alignment of binding sites pointing toward a central pore is used to combine selectivity via precise bonding in the selectivity filters with high speed multi-ion hopping translocation along pore-aligned recognition sites, as mostly demonstrated within cation-channels. However, so far the combination of selective anion recognition via hydrogen bonding, ion-pairing and anion-dipole interaction with high rate anion-π oriented translocation is not known among artificial anion channels. The possibility to create synergetic selectivity/translocation functions within anion channels is therefore attractive and interesting.

Within this context, Prof. Barboiu and coworkers discovered that protonated amino-triazole (TH+) amphiphiles could form self-assembled anion channels of stacked triazole-quartets T4 mutually stabilized by inner H-bonded anions. As shown in Figure [left], the templating H-bonded anions are strongly interacting via anion-π interactions with triazoles of vicinal quartets that self-direct their translocation along anion-selective T4 pores. The distance between anions and triazole centroid is 3.2-3.7 Å, indicating rather strong anion-π contacts. This amazing combination of classical H-bonding/ion pairing with non-classical anion-π interactions generates channels with interior free void pore openings for anion binding averaging 3 to 4 Å wide and 9-10 Å length. The robustness of the pores is simultaneously strengthened by an environmentally hydrophobic and protective outshell.

Subsequently they studied the transport activity of channels by protonated triazoles with different size through vesicle-based fluorescence assays, and hence concluded channels’ transport mechanism [Figure right a, b]. Patch-Clamp experiments also unambiguously evidenced the existence of channel pore within the lipid membrane. These results suggest a significant step forward toward the development of electrogenic anion channels with high selectivity.

This work was well supported by NSFC (National Natural Science Foundation of China, 21720102007), Agence Nationale de la Recherche ANR-15-CE29-0009 DYNAFUN and Lehn Institute of Functional Materials.

Access to this paper: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201904808