Transformation of β-Lactam Antibacterial Agents during Aqueous Ozonation: Reaction Pathways and Quantitative Bioassay of Biologically-Active Oxidation Products
Transformation of β-Lactam Antibacterial Agents during Aqueous Ozonation: Reaction Pathways and Quantitative Bioassay of Biologically-Active Oxidation Products
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DOI：
10.1021/es101061w
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发表时间：
2010-08-01
影响因子：
11.4
通讯作者：
von Gunten, Urs
中科院分区：
文献类型：
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作者：
Dodd, Michael C.;Rentsch, Daniel;von Gunten, Urs
臭氧（O-3）与β-内酰胺类抗生素青霉素G（PG）和头孢氨苄（CP）的反应先前已被发现产生保留抗菌活性的产物。这些产物在此明确鉴定为各母体分子的立体异构（R）-亚砜，并通过化学分析和抗菌活性测定的组合进行表征。PG-（R）-亚砜，其效力与PG本身的15%相似，以类似于55%的产率形成，而CP-（R）-亚砜，其活性与CP的83%相似，以最大类似于34%的产率形成。PG-（R）-亚砜不容易被O-3进一步氧化，但容易被羟基自由基（HO中心点）转化，k（HO中心点）（，app）（N）= 7.4 × 10（9）M（-1）s（-1），pH 7），导致其抗菌活性定量消除。相比之下，CP-（R）-亚砜被O-3和HO中心点降解（k”（O3，app）= 2.6 × 10（4）M-1 s（-1）和k”（HO中心点，app）= 7.6 × 10（9）M-1 s（-1），pH 7），导致其抗菌活性的定量消除。在臭氧氧化二级城市污水出水样品的过程中，（pH 8.1，C-DOC = 4.0 mg/L，[碱度] = 3.6 mM，以HCO 3-计）加标[PG]（0）= 1 μ M，O-3剂量高达100 μ M时，PG-（R）-亚砜产量不超过0.15 μ M（4.8 mg/L），但达到0.47 μ M与10 mM t-BuOH作为HO中心点清除剂添加。相比之下，在存在或不存在t-BuOH的情况下，对于加标[CP]（0）= 1 μ M的相同废水，CP-（R）-亚砜产率不超过0.1 μ M，表明CP-（R）-亚砜转化主要由与O-3的直接反应控制。这些发现表明，对于给定程度的母体化合物转化，PG-（R）-亚砜产率可能在以低O-3需求和高HO中心点清除率为特征的废水分区期间最大，而CP-（R）-亚砜产率将较少依赖于基质。在废水处理过程中青霉素的完全失活可能需要比头孢菌素失活所需的更高的O-3暴露。
Reactions of ozone (O-3) with the beta-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 similar to 15% as potent as PG itself, is formed in similar to 55% yield, whereas CP-(R)-sulfoxide, which is similar to 83% as active as CP, is formed with a maximum similar to 34% yield. PG-(R)-sulfoxide is recalcitrant toward further oxidation by O-3, but readily transformed by hydroxyl radical (HO center dot) k(HO center dot)(,app)(N) = 7.4 x 10(9) M(-1)s(-1), pH 7), resulting in quantitative elimination of its antibacterial activity. In contrast CP-(R)-sulfoxide is degraded by both O-3 and HO center dot (k"(O3,app) = 2.6 x 10(4) M-1 s(-1) and k"(HO center dot,app) = 7.6 x 10(9) M-1 s(-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 mu M, PG-(R)-sulfoxide yields did not exceed 0.15 mu M for O-3 doses up to 100 mu M (4.8 mg/L), but reached 0.47 mu M with 10-mM t-BuOH added as a HO center dot scavenger. In contrast, CP-(R)-sulfoxide yields did not exceed 0.1 mu M for the same wastewater spiked with [CP](0) = 1,mu M in either the presence or absence of t-BuOH, indicating that CP-(R)-sulfoxide transformation is governed primarily by direct reaction with O-3. These findings suggest that, for a given degree of parent compound transformation, PG-(R)-sulfoxide yields would likely be greatest during zonation of wastewaters characterized by low O-3 demands and high HO center dot 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 O-3 exposures than necessary for deactivation of cephalosporins.