The majority of the tetralactam series possessed extremely high transport activity, particularly the transporters with the highest degree of fluorination. Transporters 1c-4c have exceptionally high transport activities and low EC50 values of 0.000078, 0.000028, 0.000044, and 0.00081 mol%, respectively (Table ). The inversion in activity of 2c > 3c is possibly due to the ability of 2c to competitively bind to a Cl -anion with slightly weaker binding interactions compared to 3c, allowing for easier guest capture and release as well as unhindered fatty acid flip-flop. Another possibility is that the decreased lipophilicity of 2c compared to 3c with CLogP values of 4.29 and 5.13, respectively (Table ), enhances membrane permeability. The natural H + /Cl -co-transporter prodigiosin has also been previously studied using the HPTS transport assay, with an EC50 value of 0.000061 mol%. The transport activities of 2c and 3c show a 2.2-and 1.4-fold increase in transport activity compared to prodigiosin, confirming the anionophores as the two most active H + /Cl -co-transporters explored using this assay.