title: Ferrate(VI) oxidation of β-lactam antibiotics: reaction kinetics, antibacterial activity changes, and transformation products.
abstract: Oxidation of β-lactam antibiotics by aqueous ferrate(VI) was investigated to determine reaction kinetics, reaction sites, antibacterial activity changes, and transformation products. Apparent second-order rate constants (kapp) were determined in the pH range 6.0-9.5 for the reaction of ferrate(VI) with penicillins (amoxicillin, ampicillin, cloxacillin, and penicillin G), a cephalosporin (cephalexin), and several model compounds. Ferrate(VI) shows an appreciable reactivity toward the selected β-lactams (kapp for pH 7 = 110-770 M(-1) s(-1)). The pH-dependent kapp could be well explained by considering species-specific reactions between ferrate(VI) and the β-lactams (with reactions occurring at thioether, amine, and/or phenol groups). On the basis of the kinetic results, the thioether is the main reaction site for cloxacillin and penicillin G. In addition to the thioether, the amine is a reaction site for ampicillin and cephalexin, and amine and phenol are reaction sites for amoxicillin. HPLC/MS analysis showed that the thioether of β-lactams was transformed to stereoisomeric (R)- and (S)-sulfoxides and then to a sulfone. Quantitative microbiological assay of ferrate(VI)-treated β-lactam solutions indicated that transformation products resulting from the oxidation of cephalexin exhibited diminished, but non-negligible residual activity (i.e., ∼24% as potent as the parent compound). For the other β-lactams, the transformation products showed much lower (<5%) antibacterial potencies compared to the parent compounds. Overall, ferrate(VI) oxidation appears to be effective as a means of lowering the antibacterial activities of β-lactams, although alternative approaches may be necessary to achieve complete elimination of cephalosporin activities.
authors: Department of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST) , Gwangju, 500-712, Republic of Korea.
authors: Anggita
authors: A
authors: Karlesa
authors: Glen Andrew D
authors: GA
authors: De Vera
authors: Michael C
authors: MC
authors: Dodd
authors: Jihye
authors: J
authors: Park
authors: Maria Pythias B
authors: MP
authors: Espino
authors: Yunho
authors: Y
authors: Lee
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D001711:Biotransformation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry; D062065:Wastewater / Q000737:chemistry; D047090:beta-Lactams / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D007501:Iron; D010636:Phenols; D062065:Wastewater; D047090:beta-Lactams; C017311:ferrate ion