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2.B.100.  The pH-sensitive Imidazole Derivitive Ion Carrier (IDIC) Family 

Imidazole-derivitized ion channels that transport chloride via self-assembly have been reported (Zheng et al. 2020, Kumar and Madhavan 2023). Based on single-crystal X-ray diffraction of imidazole derivative 3, an ion-binding channel formed by a hydrogen-bonding interaction between two histidine units. This self-assembly is capable of trapping water/chloride in a void of about 5 Å. The transport activities of imidazole derivatives 1 and 2 were found to be good at pH 7.4, decreased at pH 8.4 and maximal at pH 11.4. The transport mechanism was found to change with pH. At lower pH, the channels are protonated and show H+/Cl co-transport (symport), suggesting a carrier mechanism. At pH 8.4, the NH groups are deprotonated, and the ion-transport activity of the neutral molecules decreases. At pH 11.4, as the concentration of OH increases Cl/OH antiport was observed (Kumar and Madhavan 2023). The molecules also showed voltage-dependent ion transport, making them uniquely dual-responsive, analogous to the natural protein, ClIC1 (see TC# 1.A.12.1.2).