Interaction of the Macrolide Antimicrobial Clarithromycin with Dissolved Humic Acid

Abstract

The association of the cationic macrolide antimicrobial clarithromycin (CLA) with dissolved Elliot soil humic acid (ESHA) was investigated as a function of solution chemistry. CLA-ESHA association was strongly pH-dependent, reaching a maximum near pH 6.5, and was modeled successfully using FITEQL as a 1:1 complexation reaction between CLA+ and discreet deprotonated acidic functional groups with pKa values of 4 and 6. Approximate order of magnitude increases in ionic strength produced approximately 10-fold decreases in CLA+ -ESHA association. Coefficients for CLA+ -ESHA association were significantly smaller in the presence of K+ vs Na+. Sorption data were well-fit by the Freundlich model; the Freundlich exponent was <1, suggesting CLA+ interacted with sites having a range of binding energies. Sorption appeared largely reversible; little sorption-desorption hysteresis was observed. The affinities of erythromycin and CLA+ for ESHA association sites were indistinguishable, suggesting interaction with specific sorption sites. Comparison of experimentally determined CLA-ESHA association coefficients with those predicted from single-parameter linear free energy relationships based on log Kow suggested limited contribution of hydrophobic interactions to CLA-ESHA association at environmentally relevant pH values. CLA-ESHA association constants were similar in magnitude (10(3.9)-10(4.6) to those of many nonpolar organic contaminants, and macroscopic binding data were consistent with cation exchange dominating CLA+ -ESHA association.