Multiple Roles of Cu(II) in Catalyzing Hydrolysis and Oxidation of β‑Lactam Antibiotics
2016-10-24T00:00:00Z (GMT) by
The widely used β-lactam antibiotics such as penicillins and cephalosporins are known to be susceptible to Cu<sup>II</sup>-catalyzed hydrolysis at their four-membered β-lactam ring. However, this study elucidates that Cu<sup>II</sup> 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 Cu<sup>II</sup> via this functional group. On the other hand, the β-lactam ring of penicillins is susceptible to Cu<sup>II</sup>-catalyzed hydrolysis, followed by oxidation of the hydrolysis product by Cu<sup>II</sup>. In contrast, the β-lactam ring of cephalosporins is susceptible to Cu<sup>II</sup>-catalyzed hydrolysis only. Solution pH influences the Cu<sup>II</sup>-promoted transformation by affecting the β-lactam and Cu<sup>II</sup> complexation through protonation/deprotonation of critical organic functional groups. When Cu<sup>II</sup> acts as an oxidant to promote the transformation of β-lactam antibiotics to yield Cu<sup>I</sup>, the overall role of Cu<sup>II</sup> appears catalytic if the reaction occurs under ambient atmospheric condition, due to quick oxidation of Cu<sup>I</sup> by oxygen to regenerate Cu<sup>II</sup>. Compared to earlier literature that largely assumed only the hydrolytic catalyst role of Cu<sup>II</sup> in promoting degradation of β-lactam antibiotics, the oxidative roles of Cu<sup>II</sup> identified by this study mark important contributions to a more accurate mechanistic understanding.