The abovementioned selectivity results indicate the rate-limiting NO3 -transport process as the determinant for the pH switchable Cl -/NO3 -exchange by PTSCs. We here propose three mechanisms that likely contribute to the high Cl -/NO3 -exchange activities of PTSCs at pH 4.5 and inhibition of Cl - /NO3 -exchange at pH 7.2. (1) In lipid-water biphasic systems, NO3 -binding to the protonated PTSCs is expected to be drastically weaker than Cl -binding. As a result, a lower solution pH is required to shift the equilibrium from the free neutral PTSC to the PTSCH + •••X -ion pair complex for NO3 -binding than for Cl -binding and therefore significant NO3 -transport only occurs at pH 4.5. (2) Alternatively, the PTSCH + might not need to facilitate NO3 -transport to give Cl -/NO3 -exchange at pH 4.5. By using an osmotic response assay, we found that HNO3 (pKa = -1.4) can diffuse through the membrane without any anion transporter at pH 4.5 (Fig. ). This process is negligible at pH 7.2 due to the low concentration of HNO3 in equilibrium with NO3 -(Fig. ). Given the extremely low NO3 -transport activities of PTSCH + (Fig.