Does lipophilicity affect the effectiveness of a transmembrane anion transporter? Insight from squaramido-functionalized bis(choloyl) conjugates.

Six squaramido-functionalized bis(choloyl) conjugates were synthesized and fully characterized on the basis of NMR ((1)H and (13)C) and ESI MS (LR and HR) data. Their transmembrane anionophoric activity was investigated in detail by means of chloride ion selective electrode technique and pyranine assay. The data indicate that this set of compounds is capable of promoting the transmembrane transport of anions presumably via proton/anion symport and anion exchange processes, and that lipophilicity in terms of clog P from 3.90 to 8.32 affects the apparent ion transport rate in a concentration-dependent fashion. Detailed kinetic analysis on the data obtained from both the chloride efflux and pH discharge experiments reveals that there may exist an optimum clog P range for the intrinsic ion transport rate. However, lipophilicity exhibits little effect on the effectiveness of this set of compounds in terms of either k2/Kdiss or EC50 values.