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 FITEQLas 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 similar to 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.