Transformation of β-Lactam Antibacterial Agents during Aqueous Ozonation: Reaction Pathways and Quantitative Bioassay of Biologically-Active Oxidation Products

• Published in: Environmental science & technology Vol. 44; no. 15; pp. 5940 - 5948
• Main Authors: Dodd, Michael C, Rentsch, Daniel, Singer, Heinz P, Kohler, Hans-Peter E, von Gunten, Urs
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-08-2010
• Subjects: Anti-Bacterial Agents - chemistry; Applied sciences; Biotransformation; Cephalexin - chemistry; Exact sciences and technology; Hydroxyl Radical - chemistry; Oxidation-Reduction; Ozone - chemistry; Penicillin G - chemistry; Pollution; Remediation and Control Technologies; Waste Disposal, Fluid - methods; Drug; Chemical analysis; Bioassay; Scavenging; Ozone; Waste water; Ozonization; Antibiotic; Reaction mechanism; Hydroxyl radicals; Urban waste water; Oxidation; Antibacterial agent; Organic compounds
• ISSN: 0013-936X; 1520-5851
• DOI: 10.1021/es101061w

Reactions of ozone (O3) with the β-lactam antibiotics penicillin G (PG) and cephalexin (CP) have previously been found to yield products retaining antibacterial activities. These products are unequivocally identified here as the stereoisomeric (R)-sulfoxides of each parent molecule and characterized by a combination of chemical analysis and an antibacterial activity assay. PG-(R)-sulfoxide, which is ∼15% as potent as PG itself, is formed in ∼55% yield, whereas CP-(R)-sulfoxide, which is ∼83% as active as CP, is formed with a maximum ∼34% yield. PG-(R)-sulfoxide is recalcitrant toward further oxidation by O3, but readily transformed by hydroxyl radical (HO•) (k HO•,app ” = 7.4 × 109 M−1s−1, pH 7), resulting in quantitative elimination of its antibacterial activity. In contrast, CP-(R)-sulfoxide is degraded by both O3 and HO• (k O3,app ” = 2.6 × 104 M−1s−1 and k HO•,app ”= 7.6 × 109 M−1s−1, pH 7), leading to quantitative elimination of its antibacterial activity. During ozonation of a secondary municipal wastewater effluent sample (pH 8.1, CDOC = 4.0 mg/L, [alkalinity] = 3.6 mM as HCO3 −) spiked with [PG]0 = 1 μM, PG-(R)-sulfoxide yields did not exceed 0.15 μM for O3 doses up to 100 μM (4.8 mg/L), but reached 0.47 μM with 10-mM t-BuOH added as a HO• scavenger. In contrast, CP-(R)-sulfoxide yields did not exceed 0.1 μM for the same wastewater spiked with [CP]0 = 1 μM in either the presence or absence of t-BuOH, indicating that CP-(R)-sulfoxide transformation is governed primarily by direct reaction with O3. These findings suggest that, for a given degree of parent compound transformation, PG-(R)-sulfoxide yields would likely be greatest during ozonation of wastewaters characterized by low O3 demands and high HO• scavenging rates, whereas CP-(R)-sulfoxide yields would be less matrix-dependent. In general, complete deactivation of penicillins during wastewater treatment will likely require higher O3 exposures than necessary for deactivation of cephalosporins.