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

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• 作者：Michael C. Dodd ; Daniel Rentsch ; Heinz P. Singer ; Hans-Peter E. Kohler ; Urs von Gunten
• 刊名：Environmental Science & Technology
• 出版年：2010
• 出版时间：August 1, 2010
• 年：2010
• 卷：44
• 期：15
• 页码：5940-5948
• 全文大小：451K
• 年卷期：v.44,no.15(August 1, 2010)
• ISSN：1520-5851

文摘

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, C_DOC = 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.