Small-molecule transmembrane anion transporters are promising anti-cancer drug candidates due to their ability to disrupt pH/anion gradients and membrane potential across cell membranes and in organelles. The research of synthetic anion transporters was initially inspired by the natural product prodigiosin which facilitates efficient H + /Cl -symport and as a result neutralizes acidic pH inside vacuolar organelles including lysosomes, endosomes and Golgi apparatus. While prodigiosin exhibits potent anion transport activity under both neutral and acidic conditions, synthetic anion transporters with pH-dependent transport activities have been designed with a potential to target the acidic intracellular environment of tumours and reduce the toxicity towards normal cells. Phenylthiosemicarbazones (PTSCs) are a class of pH-switchable anion transporters previously reported to exhibit up to 640-fold increase in chloride/nitrate exchange activity on going from pH 7.2 to 4.0. This pH dependence was regulated by protonation of the imine nitrogen at acidic pH, which led to a conformational switch of the thiourea motif from an inactive anti-conformation to an active anion binding syn-conformation (Fig. ). For a better understanding of anion transport and pH switching mechanism of this class of transporters, we decided to study an expanded library of PTSCs and here report our serendipitous discovery of their extremely high halide over oxyanion transport selectivity leading to the pH-switchable chloride/nitrate exchange being regulated by the rate-limiting nitrate transport process.