Anion Transport in Red Blood Cells I. Chemical Properties of Anion Recognition Sites as Revealed by Structure-Activity Relationships of Aromatic Sulfonic Acids

Abstract

The present study is concerned with the chemical factors that determine the inhibitory properties of reversible aromatic sulfonic acids on sulfate exchange system of human red blood cells. Two series of compounds were tested for in hibitory potencies: benzene sulfonic acid (BS) and 2,2′-disulfonic stilbene (DS) derivatives, each series with substituent groups such as C1, OH, NHz, NOz, N″, N-acetamido, and N-benzoamido. As judged by various kinetic criteria, all congeners of BS and DS appear to have common sites of action in the anion transport system. The range of inhibitory potencies, as defined by the concentration required to produce 50% inhibition (ID50), varied over a lo4 range (ID5,: 2-50,000 PM). The degree of inhibition was correlated with two physicochemical properties of the substituent groups: (a) lipophilicity, as judged by the T values (Hansch factor) of the groups; and (b) the electronic character, as judged by u values (Hammett factor) of the groups. Optimal correlations were obtained with a linear combination of the two factors. Based on the above structure-activity relationships and on a comparison between the inhibitory properties of congeners of BS and DS, we suggest that the microenvironment of substrate recognition sites bears a positive multipolar character and possesses functionally essential groups with electron donor capacity embedded in a hydrophobic area.

Key Words:

• anion transport
• red blood cells
• membranes
• structure-activity relationships
• chemical probes
• membrane structure function