Boronic acids facilitate the transport of ribonucleosides through lipid bilayers

Boronic acids were found to facilitate the transport of various ribonucleosides in and out of liposomes (artificial cells). Most experiments were conducted with large unilamellar vesicles composed of dipalmitoylphosphatidyl choline, cholesterol, and phosphatidic acid in the ratio 20:15:2. Rates of nucleoside efflux were determined by a UV assay, whereas the influx experiments used a radiotracer method. Five boronic acids were studied: 3,5-bis(trifluoromethyl)phenylboronic acid (1), 3,5-dichlorophenylboronic acid (2), 4-tert-butylphenylboronic acid (3), 1-butylboronic acid (4), and 4-carboxyphenylboronic acid (5). The order of carrier effectiveness was found to be 1 > 3 > 2 >> 4 >> 5. Efflux and influx experiments with mixtures of nucleosides and sucrose showed virtually complete transport selectivity in favor of the nucleosides. Mechanistic studies indicate that the nucleoside transport mechanism involves transient formation of a lipophilic, trigonal boronate ester.