||Using the chemical versatility of the benzo[b]thiophene motif, an extensive library of 24 (thio)urea receptors, with different binding properties and lipophilicities, was prepared and included alpha,alpha-, alpha,beta-, beta,beta-, beta,gamma-, alpha,gamma-, and gamma,gamma-benzo[b]thiophene positional isomers, as well as beta or gamma-benzo[b]thiophene-based molecules decorated with aliphatic chains or aryl moieties with different fluorination degrees. H-1 NMR titrations, X-ray crystallo-graphic studies, and DFT calculations were used to study the chloride binding affinities between receptors and substrates. Experimental efflux studies suggested that the anion transmembrane transport activity is dependent on the receptors lipophilicity and hydrogen bonding ability. Moreover, LUV based assays indicated that anion efflux occurs mainly through an uniport mechanism. Further MD simulations showed that anion transport is highly dependent on the orientation and interactions of the receptors at the water/lipid interface.