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There has been a tremendous evolution for artificial ion transport systems, especially gated synthetic systems, which closely mimic their natural congeners. Herein, we demonstrate a trans‐azobenzene‐based photoregulatory anionophoric system that transports chloride by forming a sandwich dimeric complex. Further studies confirmed a carrier‐mediated chloride‐anion antiport mechanism, and the supramolecular interactions involved in chloride recognition within the sandwich complex were revealed from theoretical studies. Reversible trans–cis photoisomerization of the azobenzene was achieved without any significant contribution from the thermal cis→trans isomerization at room temperature. Photoregulatory transport activity across the lipid bilayer membrane inferred an outstanding off‐on response of the azobenzene photoswitch. [ABSTRACT FROM AUTHOR]

Acidic microenvironments in solid tumors are a hallmark of cancer. Inspired by that, we designed a family of pseudopeptidic cage‐like anionophores displaying pH‐dependent activity. When protonated, they efficiently bind chloride anions. They also transport chloride through lipid bilayers, with their anionophoric properties improving at acidic pH, suggesting an H+/Cl− symport mechanism. NMR studies in DPC micelles demonstrate that the cages bind chloride within the lipid phase. The chloride affinity and the chloride‐exchange rate with the aqueous bulk solution are improved when the pH is lowered. This increases cytotoxicity towards lung adenocarcinoma cells at the pH of the microenvironment of a solid tumor. These properties depend on the nature of the amino‐acid side chains of the cages, which modulate their lipophilicity and interactions with the cell membrane. This paves the way towards using pH as a parameter to control the selectivity of cytotoxic ionophores as anticancer drugs. [ABSTRACT FROM AUTHOR]