TRANSPORT OF GLYCOSIDES THROUGH LIQUID ORGANIC MEMBRANES MEDIATED BY REVERSIBLE BORONATE FORMATION IS A DIFFUSION-CONTROLLED PROCESS

The ability of phenylboronic acid, [3-(1-adamantylcarboxamido)phenyl]boronic acid, and diphenylborinic acid to extract and transport p-nitrophenyl beta-D-glucopyranoside (glucoside), p-nitrophenyl beta-D-galactopyranoside (galactoside), and p-nitrophenyl beta-D-mannopyranoside (mannoside) through a liquid organic membrane, in the presence of trioctylmethylammonium or tetrabutylammonium chloride, was determined. Under the conditions examined, glycoside transport was facilitated by the reversible formation of covalent tetrahedral, anionic glycoside-boronate complexes, which partitioned into the organic membrane as lipophilic ion pairs. The results of various experiments indicated the rate-limiting step in the transport process was diffusion of the solutes through the narrow unstirred boundary layers adjacent the organic/aqueous interfaces. A plot of glycoside transport rate versus glycoside extraction constant, K-ex, formed an approximate bell-shaped relationship. Maximal transport occurred when the carrier admixture had an extraction constant of log K-ex(max) similar to 2.2. Under low extraction conditions (K-ex < K-ex(max)), movement of the glycoside from the receiving phase into the organic membrane was the rate-determining step, and under high extraction conditions (K-ex > K-ex(max)), exit from the membrane into the receiving phase was rate-determining. Because transport was dependent on K-ex, an analysis of the structural and environmental factors that controlled transport could be reduced to an analysis of the factors that changed K-ex relative to K-ex(max). The factors examined included the following; pH, boron acid acidity, diol structure, polarity of the organic layer, boron acid lipophilicity, glycoside lipophilicity, quaternary ammonium lipophilicity, and the presence of competing lipophilic anions. The importance of K-ex(max) as the parameter determining transport stereoselectivity is discussed.