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 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.
Sibley
Samuel D
SD
Environmental Chemistry and Technology Program, and Department of Soil Science, University of Wisconsin, Madison, Wisconsin 53706, USA.
Pedersen
Joel A
JA
D020003:1-Octanol / Q000737:chemistry; D000327:Adsorption; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D017291:Clarithromycin / Q000737:chemistry*; D004917:Erythromycin / Q000737:chemistry; D006812:Humic Substances; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D014867:Water / Q000737:chemistry
D000900:Anti-Bacterial Agents; D006812:Humic Substances; D014867:Water; D004917:Erythromycin; D017291:Clarithromycin; D020003:1-Octanol