Dodd Michael C, Shah Amisha D, von Gunten Urs, Huang Ching-Hua
Swiss Federal Institute of Aquatic Science and Technology (EAWAG), Duebendorf, Switzerland.
Environ Sci Technol. 2005 Sep 15;39(18):7065-76. doi: 10.1021/es050054e.
Kinetics, products, and mechanistic aspects of reactions between free available chlorine (HOCl/OCl-), ciprofloxacin (CF), and enrofloxacin (EF) were extensively investigated to elucidate the behavior of fluoroquinolone antibacterial agents during water chlorination processes. Although the molecular structures of these two substrates differ only with respect to degree of N(4) amine alkylation, CF and EF exhibit markedly different HOCl reaction kinetics and transformation pathways. HOCI reacts very rapidly at CF's secondary N(4) amine, forming a chloramine intermediate that spontaneously decays in aqueous solution by concerted piperazine fragmentation. In contrast, HOCl reacts relatively slowly at EF's tertiary N(4) amine, apparently forming a highly reactive chlorammonium intermediate (R3N-(4)Cl+) that can catalytically halogenate EF or other substrates present in solution. Flumequine, a fluoroquinolone that lacks the characteristic piperazine ring, exhibits no apparent reactivity toward HOCI but appears to undergo facile halodecarboxylation in the presence of R3N(4)-Cl+ species derived from EF. Measured reaction kinetics were validated in real water matrixes by modeling CF and EF losses in the presence of free chlorine residuals. Combined chlorine (CC) kinetics were determined under selected conditions to evaluate the potential significance of reactions with chloramines. CF's rapid kinetics in direct reactions with HOCl, and relatively high reactivity toward CC, indicate that secondary amine-containing fluoroquinolones should be readily transformed during chlorination of real waters, whether applied chlorine doses are present as free or combined residuals. However, EF's slower HOCl reaction kinetics, recalcitrance toward CC, and participation in the catalytic halogenation cycle described herein suggest that tertiary amine-containing fluoroquinolones will be comparatively stable during most full-scale water chlorination processes.
为阐明氟喹诺酮类抗菌剂在水氯化过程中的行为，对游离有效氯（HOCl/OCl-）、环丙沙星（CF）和恩诺沙星（EF）之间反应的动力学、产物及机理进行了广泛研究。尽管这两种底物的分子结构仅在N(4)胺烷基化程度上有所不同，但CF和EF表现出明显不同的HOCl反应动力学和转化途径。HOCl在CF的仲N(4)胺处反应非常迅速，形成一种氯胺中间体，该中间体在水溶液中通过协同的哌嗪断裂自发衰变。相比之下，HOCl在EF的叔N(4)胺处反应相对较慢，显然形成了一种高活性的氯铵中间体（R3N-(4)Cl+），它可以催化卤化EF或溶液中存在的其他底物。氟甲喹是一种缺乏特征性哌嗪环的氟喹诺酮，对HOCl没有明显的反应活性，但在存在源自EF的R3N(4)-Cl+物种时似乎容易发生卤代脱羧反应。通过模拟游离氯残留存在下CF和EF的损失，在实际水基质中验证了测得的反应动力学。在选定条件下测定了结合氯（CC）动力学，以评估与氯胺反应的潜在重要性。CF与HOCl直接反应的快速动力学以及对CC的相对高反应活性表明，含仲胺的氟喹诺酮在实际水氯化过程中应易于转化，无论应用的氯剂量是以游离残留还是结合残留形式存在。然而，EF较慢的HOCl反应动力学、对CC的顽固性以及参与本文所述的催化卤化循环表明，含叔胺的氟喹诺酮在大多数全规模水氯化过程中将相对稳定。
