Comparison of chlorination behaviors between norfloxacin and ofloxacin: Reaction kinetics, oxidation products and reaction pathways

Highlights

• The maximum k_app of NOR were 4 orders of magnitude higher than that of OFL.

• The reactions of deprotonated FQs species with HClO dominant the total reaction.

• The quinolone ring of tertiary amine FQ opened after halodecarboxylation.

Abstract

Fluoroquinolones (FQs) are very ubiquitous in water environment in China. The commonly application of free available chlorine (FAC) during water treatment stimulated the focus on the transformation of FQs during chlorination. Among these FQs, norfloxacin (NOR) and ofloxacin (OFL) are the representatives of secondary amine FQs and tertiary amine FQs, respectively. To better understand the difference between secondary amine FQs and tertiary amine FQs during chlorination, reaction kinetics, products and mechanisms were determined. The maximum k_app of NOR were four orders of magnitude higher than that of OFL. Moreover, eleven products of NOR and twelve products of OFL were obtained by LC−MS/MS analysis. For the two FQs, the common reactive sites were three nitrogen atoms, benzene ring, carboxyl group and double bond by chlorination. For OFL, the ether ring was also active in aqueous system. The formation mechanisms of these products were presented in this study. The main reaction pathways were electrophilic addition to nitrogen, nucleophilic substitution to benzene ring, halodecarboxylation of carboxyl group and hydrolysis of ether ring. Na₂S₂O₃ as a reducing agent had large effect on the chlorination of secondary amine FQ, but no effect on tertiary amine FQ. Be different to secondary amine FQ, the opening of quinolone ring happened in tertiary amine FQ after halodecarboxylation of carboxyl group.

Introduction

Fluoroquinolones (FQs), piperazinyl derivatives of quinolone, are a group of broad spectrums of antibiotics clinically prescribed (Sayin et al., 2018). The total usage of FQs was about 27300 tons each year in seven regions of China (Zhang et al., 2015). Due to mass production and abuse and incomplete metabolism in creature body, a large fraction of FQs were discharged into municipal wastewater systems (Van Doorslaer et al., 2014). The most frequently detected FQs in aquatic environment were norfloxacin (NOR) and ofloxacin (OFL) and ciprofloxacin (CIP) in China (Wang et al., 2014). It was showed that the concentrations of OFL and NOR were 438–1106 ng/L and 227–708 ng/L respectively in municipal wastewater effluent (Li et al., 2014; Archer et al., 2017). The discharge of wastewater resulted in frequent detection of FQs in surface water of 66–460 ng/L (Xu et al., 2007), groundwater of ND-16249 ng/L (Sui et al., 2015), even drinking source water of 90–216 ng/L (Jiang et al., 2018) and tap water of 1–680 ng/L (Yiruhan et al., 2010). All the quinoline compounds showed significant genotoxic potential (Hu et al., 2007), which might expose human beings to potential risks.

Significant removals of FQs were observed during oxidation treatment such as ozone (Ling et al., 2018), chlorine dioxide (Wang et al., 2010), free chlorine (FAC) (Dodd et al., 2005; Yassine et al., 2017; Zhang et al., 2017) and potassium permanganate (Xu et al., 2016), though the removal of FQs was not considered intentionally in the design of treatment unit. Considering the prevalence of chlorine in municipal wastewater and drinking water treatment process, chlorination reaction would be very important for the fate of FQs in the water environment. The degradation of NOR by FAC disinfection was surveyed in municipal wastewater and in marine water (Li and Zhang, 2012; Zhang et al., 2017). The degradation of OFL by chlorination was also be investigated (Li and Zhang, 2012; Gudaganatti et al., 2012; El Najjar et al., 2013; Yassine et al., 2017). Dodd et al. (2005) reported that species-specific reaction kinetics of CIP and ENR with aqueous chlorine containing FAC and combined chlorine (CC).

Abia et al. (1998) compared the chlorination behaviors of secondary and tertiary aliphatic amines and found that the k values of secondary amines were at least 2 orders of magnitude higher than that of tertiary amines. In addition, it was found that the k value usually reached the maximum value when the pH value was between the pKa value of HClO and the pKa value of phenol or amines (Pinkston and Sedlak, 2004).

A slower removal of OFL (k_app = 26 M-1s-1) was noted when Na₂S₂O₃ was used to stop the chlorination reaction compared to the degradation observed without using a reducing agent (k_app = 4400 M-1s-1) (Negreira et al., 2015). Moreover, Pinkston and Sedlak, 2004 mentioned that the chlorinated products of secondary amine-containing pharmaceuticals would convert back into the parent compounds by reaction with Na₂S₂O₃. However, Na₂S₂O₃ has no effect on the chlorination kinetic of OFL in Yassine's et al. (2017) experiment results. It might be due to the different reducing reaction mechanisms by for the chlorination products of secondary and tertiary amines with Na₂S₂O₃.

Almost all fluoroquinolones contain the structures of aromatic amines (Hu et al., 2007). It is significant to compare the chlorination behaviors of secondary and tertiary amine based FQs. During chlorination, pharmaceuticals may undergo oxidation/substitution reactions yielding disinfection byproducts. Halogenated aromatic DBPs were detected in the chlorinated saline secondary sewage effluent by UPLC/ESI-tqMS (Yang and Zhang, 2013) Brominated disinfection byproducts were measured during chlorination of saline sewage effluents (Ding et al., 2013). Transformation of tamoxifen and its major metabolites was investigated during chlorination (Negreira et al., 2015). In this research, the reaction kinetics, oxidation products and reaction pathways were determined to elucidate the fate of NOR and OFL during chlorination. As shown in Table 1, each FQ has two pKas related to carboxyl and N4 atom in piperazine moiety. The “species-specific” second-order rate constants with FAC were also determined. The effects of FAC concentration, reaction time and nucleophilic sulfur compound of Na₂S₂O₃, on the formation of oxidation products were also discussed.