Oxidative Transformation of Cephalosporin Antibiotics by Manganese Dioxides: Structure vs Reactivity
Date Issued
2015
Date
2015
Author(s)
Chen, Yung-En
Abstract
Oxidative transformation could be an important degradation pathway for cephalosporin antibiotics in natural surface water environments. Five cephalosporin antibiotics, cefotaxime (CTX), cephalexin (CFX), cephradine (CFD), cephapirin (CFP), and cefazolin (CFZ), were selected as target compounds to study their environmental fates. Synthetic δ-MnO2 was used in this study, and all reactions were conducted in batch experiments. Oxidation on the core structure (7-aminodesacetoxycephalosporanic acid, 7-ADCA) by MnO2 was the main degradation pathway for CFX; therefore, CFX was chosen as a representative compound for further reaction mechanism study. The results showed that the oxidation of CFX (at concentrations of 100 ppb to 2 ppm) fits the Langmuir-type equilibrium and reaction model, which was proposed based on the adsorption and electron transfer steps. The oxidation on the core and substructures by MnO2 was investigated, and the formed byproducts from oxidation were examined to elucidate the reactivities of the five target compounds and to identify the positions where oxidation occurs. The results indicated that the core structure (7-ADCA moiety) of cephalosporin is one oxidation site for MnO2 oxidation, and the oxidation on the core structure resulted in smaller fragments (shown in the case of CFX and CFZ). The substituent in the C-3 position of the cephem ring could change the reactivity of the core structure (i.e., 7-ADCA and CFZ); however, the substituent in the C-7 position does not change the reactivity of the core structure. The oxidation position of CFX mainly occurs in the core structure, while CTX, CFD, and CFP oxidation mainly occur in the substructures attached to the C-7 position of the cephem ring (2-amino-α-(methoxyimino)-4-thiazolylacetyl group (2-AMTA), dienylglycylamino group (DGA), 2-pyridin-4-ylsulfanylacetyl group (2-PSA), respectively). In CFP, bond breaking likely occurs at the amide bond of the C-7 substituent. In CFZ, the 1-M moiety is not the oxidation site of degradation. Furthermore, the reactivities of the substructures decrease as follows: 2-AMTA > 2-PSA > DGA > 7-ADCA > phenylglycylamino group ≈ 1-methyltetrazole (inert to oxidation). The total organic carbon content remained constant throughout the MnO2 reaction, indicating that no mineralization occurred and that the reaction was merely a transformation process. Although the resultant byproducts showed no Microtox toxicity, they were more resistant to further MnO2 oxidation. Sunlight, another important environmental factor that may affect the oxidation mechanisms of MnO2, was also studied in this work. For CFX, CFD, and CTX, photo-assisted oxidative degradation was predominated by MnO2 oxidation. However, for CFZ, the overall degradation was predominated by direct photolysis. Although enhanced CFX, CFD, CFZ, and CTX oxidation was not obvious under the current experimental conditions, sunlight significantly increased the initial dissolution rate of MnO2 (by a factor of eight).
Subjects
Cephalosporin
Manganese oxides
Oxidative degradation
Photo assisted oxidation
Cephem ring
Type
thesis
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