Tuesday, November 14, 2006

Interaction of Clarithromycin with Dissolved Humic Acid.

Sam Sibley, Univ of Wisconsin, Environmental Chemistry and Technology Program, 1525 Observatory Drive, Madison, WI 53706-1299 and Joel Pedersen, Univ of Wisconsin, Dept of Soil Science, 1525 Observatory Drive, Madison, WI 53706-1299.

Macrolide antimicrobials are among the highest prescribed human pharmaceuticals and are employed both therapeutically and non–therapeutically (i.e., as feed additives) for livestock and poultry. These compounds have been detected increasingly in agricultural and environmental reservoirs from 0.1 – 1000 ng L-1. Their presence in these media may have negative ecological impacts and has been implicated as a potential agent in the spread of antibiotic resistance. However, the risk associated with the environmental occurrence of these compounds is unclear, in part, because an adequate database of fate and transport data is lacking. In particular, the influence of colloidal/dissolved organic matter (COM) on the environmental transport of these agents, especially those derived from carbon–rich agricultural sources, may be important but is largely unknown. Therefore, we investigated the interaction of H3–labeled clarithromycin, a semi-synthetic derivative of erythromycin, with dissolved Elliot soil humic acid. We determined Ddoc values using equilibrium dialysis over a range of environmentally relevant proton activities and solution chemistries. CLAR association with EHA (1) reaches a maximum at near-neutral pH values; (2) is well described by the Freundlich model; (3) is reversible; (4) decreases with increasing concentrations of competing molecules (e.g., erythromycin); and (5) is larger than predicted by hydrophobic partitioning alone. Overall, these trends suggest the importance of electrostatic interactions and hydrogen-bonding for CLAR association with COM. For example, CLAR association with EHA increases from pH 4–6.3, while CLAR remains predominately cationic and deprotonation of EHA carboxylic acids result in electrostatic attraction. Ddoc decreases above pH 6.3, as the neutral form of CLAR becomes more abundant and the charge of EHA carboxylic acid and phenolic moieties becomes increasingly negative. Furthermore, deprotonation of EHA diminishes its H–bond–donating capacity and decreases its interaction with CLAR, which possesses an abundance of H–bond accepting oxygen functional groups.