18 research outputs found
Ferrate(VI) Oxidation of β‑Lactam Antibiotics: Reaction Kinetics, Antibacterial Activity Changes, and Transformation Products
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 (<i>k</i><sub>app</sub>) 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
(<i>k</i><sub>app</sub> for pH 7 = 110–770 M<sup>–1</sup> s<sup>–1</sup>). The pH-dependent <i>k</i><sub>app</sub> 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 (<i>R</i>)- and (<i>S</i>)-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