Interaction of the Macrolide Antimicrobial Clarithromycin with Dissolved Humic Acid

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 pK_a values of 4 and 6. Approximate order of magnitude increases in ionic strength produced 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 K_ow 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.