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Multiple Roles of Cu(II) in Catalyzing Hydrolysis and Oxidation of β‑Lactam Antibiotics
journal contribution
posted on 2016-10-24, 00:00 authored by Jiabin Chen, Peizhe Sun, Yalei Zhang, Ching-Hua HuangThe widely used β-lactam antibiotics
such as penicillins
and cephalosporins are known to be susceptible to CuII-catalyzed
hydrolysis at their four-membered β-lactam ring. However, this
study elucidates that CuII can in fact play multiple roles
in promoting the hydrolysis and/or oxidation of β-lactam antibiotics
under environmental aquatic conditions (pH 5.0–9.0 and 22 °C),
depending on β-lactams’ structural characteristics and
solution pH. Most significantly, the β-lactam antibiotics that
contain a phenylglycine primary amine group on the side chain can
undergo direct oxidation by CuII via this functional group.
On the other hand, the β-lactam ring of penicillins is susceptible
to CuII-catalyzed hydrolysis, followed by oxidation of
the hydrolysis product by CuII. In contrast, the β-lactam
ring of cephalosporins is susceptible to CuII-catalyzed
hydrolysis only. Solution pH influences the CuII-promoted
transformation by affecting the β-lactam and CuII complexation through protonation/deprotonation of critical organic
functional groups. When CuII acts as an oxidant to promote
the transformation of β-lactam antibiotics to yield CuI, the overall role of CuII appears catalytic if the reaction
occurs under ambient atmospheric condition, due to quick oxidation
of CuI by oxygen to regenerate CuII. Compared
to earlier literature that largely assumed only the hydrolytic catalyst
role of CuII in promoting degradation of β-lactam
antibiotics, the oxidative roles of CuII identified by
this study mark important contributions to a more accurate mechanistic
understanding.