The addition of the series to vesicles not treated with an additional cationophore resulted in negligible enhancements in Cl - efflux. The kini rates were shown to increase concordantly with the Cl -binding constants, most likely due to stronger binding affinities, which allowed for better anion recognition and binding in a competitive environment. As a result, each sub-series conformed to the kini rate order of 4,5-difluorophenylene-> phenylene-> naphthalene-linked tetralactams (c > a > b). Over the series, only the t-Bu-phenylene-linked transporter (4a) had an ENC factor below 1.3, indicating that the main transport pathway was via the electroneutral co-transport mechanism (Table ). The kini rates obtained in untreated vesicles and vesicles treated with Vln were very similar for most of the series, indicating that the series does not operate via an electrogenic Cl -pathway. Interestingly, the transporters containing higher degrees of fluorination displayed ENC factors of ≥ 3 (Table ). The CF3substituted transporter containing the 4,5-difluorophenylene-linker (3c) was highly active and had to be tested at a 100-fold lower concentration of 0.0005 mol% compared to 3a or 3b (0.05 mol%). Even at a reduced concentration, tests still resulted in extremely high electroneutral transport activity with a kini = 0.25 mol% (Table ).