Multiple Roles of Cu(II) in Catalyzing Hydrolysis and Oxidation of β-Lactam Antibiotics
Multiple Roles of Cu(II) in Catalyzing Hydrolysis and Oxidation of β-Lactam Antibiotics
复制标题
DOI：
10.1021/acs.est.6b02702
复制
发表时间：
2016-11-15
影响因子：
11.4
通讯作者：
Huang, Ching-Hua
中科院分区：
文献类型：
--
作者：
Chen, Jiabin;Sun, Peizhe;Huang, Ching-Hua
广泛使用的β-内酰胺类抗生素，如青霉素和头孢菌素，在其四元β-内酰胺环上对铜-II催化的水解很敏感。然而，这项研究阐明了在环境水生条件下(pH 5.0-9.0和22℃)，根据β-内酰胺类抗生素的结构特征和溶液pH，铜-II实际上可以在促进β-内酰胺类抗生素的水解和/或氧化方面发挥多重作用。最重要的是，侧链上含有苯甘氨酸伯胺基团的β-内酰胺类抗生素可以通过这个官能团被铜-II直接氧化。另一方面，青霉素类的β-内酰胺环容易被铜-Ⅱ催化的水解，然后被铜-Ⅱ氧化。相反，头孢菌素的β-内酰胺环只对铜-II催化的水解敏感。溶液pH通过影响β-内酰胺和关键有机官能团的质子化/去质子化来影响铜-II促进的转化。当铜-II作为氧化剂促进β-内酰胺类抗生素转化为铜-I时，如果反应发生在常压条件下，由于铜-I被氧气快速氧化生成铜-II，铜-II的总体作用表现为催化作用。与早期文献大多假设铜-II在促进β-内酰胺类抗生素降解中只起水解性催化剂作用不同，本研究确定的铜-II的氧化作用标志着对更准确的机理理解的重要贡献。
The widely used beta-lactam antibiotics such as penicillins and cephalosporins are known to be susceptible to Cu-II-catalyzed hydrolysis at their four-membered beta-lactam ring. However, this study elucidates that Cu-II can in fact play multiple roles in promoting the hydrolysis and/or oxidation of beta-lactam antibiotics under environmental aquatic conditions (pH 5.0-9.0 and 22 degrees C), depending on beta-lactams' structural characteristics and solution pH. Most significantly, the beta-lactam antibiotics that contain a phenylglycine primary amine group on the side chain can undergo direct oxidation by Cu-II via this functional group. On the other hand, the beta-lactam ring of penicillins is susceptible to Cu-II-catalyzed hydrolysis, followed by oxidation of the hydrolysis product by Cu-II. In contrast, the beta-lactam ring of cephalosporins is susceptible to Cu-II-catalyzed hydrolysis only. Solution pH influences the Cu-II-promoted transformation by affecting the beta-lactam and Cu-II complexation through protonation/deprotonation of critical organic functional groups. When Cu-II acts as an oxidant to promote the transformation of beta-lactam antibiotics to yield Cu-I, the overall role of Cu-II appears catalytic if the reaction occurs under ambient atmospheric condition, due to quick oxidation of Cu-I by oxygen to regenerate Cu-II. Compared to earlier literature that largely assumed only the hydrolytic catalyst role of Cu-II in promoting degradation of beta-lactam antibiotics, the oxidative roles of Cu-II identified by this study mark important contributions to a more accurate mechanistic understanding.