Consistent with previous findings, the new PTSCs 1-9 induced efficient Cl -efflux with monensin and low-to-negligible Cl -efflux with valinomycin at pH 4.5 (Fig. blue, Table ), indicating the strong preference for H + /Cl -symport over Cl -uniport for these transporters. Significant Cl -uniport activities (relative to H + /Cl -symport activities), however, could be observed for polyfluorinated transporters 6, 8 and 9 at pH 7.2. This can be attributed to the neutral form of PTSCs facilitating Cl -uniport via Cl - binding in the anti-conformation (Fig. left) followed by transmembrane diffusion of the anionic complex, release of Cl -and the back diffusion of the neutral uncomplexed PTSC. This alternative mechanism required a significant anion binding affinity of the neutral form (in which only one thiourea NH and a weak imine CH donor are available for anion binding) and therefore was only observed for the more acidic transporters in the series. Surprisingly, while these PTSCs are inactive Cl -/NO3 -exchangers at pH 7.2, we observed significant H + /Cl -symport (coupling to monensin) for all transporters at pH 7.2 (Fig. red, Table ). Notably for transporters 1, 2, 3 and 7 (the best pH-switchable Cl -/NO3 -exchangers among transporters studied in this paper), the rate of H + /Cl -symport at pH 7.2 is similar to or even faster than Cl -/NO3 -exchange at pH 4.5 (Figs. S56, S57, S58, S62). These results suggest that the PTSCs are already capable of H + /Cl - symport at pH 7.2, contrasting the "switch-OFF" of Cl -/NO3 -exchange at pH 7.2 (Fig. , Table ).