Study of free nitrous acid (FNA)-based elimination of sulfamethoxazole: Kinetics, transformation pathways, and toxicity assessment

Highlights

• FNA-based elimination of SMX was comprehensively evaluated.

• FNA showed specific efficacy on sulphonamides.

• SMX degradation was described by $d\left[SMX\right]/\text{dt}=-0.29e^{-1.69pH}{\left[SMX\right]}^{0.945}{\left[FNA\right]}^{1.35}$.

• Nitrosubstitution, deamination, and sulfonamide bond cleavage were dominant transformation pathways.

• Transformation products showed toxicity, but no antibacterial activity.

Abstract

Free nitrous acid (FNA)-based applications have been broadly adopted in the development of novel wastewater management technologies, but a basic understanding of the effect of the chemical properties of FNA on the elimination of micropollutants is still lacking. This study aims to comprehensively evaluate FNA-based elimination of sulfamethoxazole (SMX), which is a typical species of sulphonamide antibiotics. Batch experiments were conducted under different influencing factors to investigate the antibiotics elimination processes. We found that FNA showed specific efficacy on sulphonamides characterized by sulfonamide and aniline functional groups, such as SMX. SMX degradation was affected by the initial SMX concentration, FNA concentration and solution pH and described by $d\left[SMX\right]/\text{dt}=-0.29e^{-1.69pH}{\left[SMX\right]}^{0.945}{\left[FNA\right]}^{1.35}$. The cationic forms of SMX were more reactive towards FNA-based active components. Sulfonamide bond (S-N or C-S bonds) cleavage, nitrosubstitution, deamination and radical oxidation were proposed to be the relevant transformation pathways. The FNA-based technique was not effective for diminishing toxicity, but this process could strongly control antibacterial activity.

Introduction

Antibiotics are effective agents for killing or inhibiting microbes, and therefore, large quantities of antibiotics have been produced and consumed to control infections in humans and animals since the discovery of penicillin in 1929 (Fleming 1929). Global antibiotics usage has been estimated to be 300,000 tons per year, with approximately 1/3 of this total used to treat humans (Wise 2002). The average metabolic rate of all antibiotics used for humans is approximately 30% (Kümmerer and Henninger 2003), so a large amount of residual antibiotics have been excreted and have entered the sewage system in either parent or metabolic forms. It is estimated that more than 8000 t of 36 commonly used antibiotics are excreted annually in China (Zhang et al. 2015). Although the removal efficiency for most antibiotics in wastewater treatment facilities is higher than 80%, their concentrations in effluent still range from ng·L⁻¹ to μg·L⁻¹ (Wu et al. 2016, Ben et al. 2018). The toxic byproducts of antibiotics may lead to changes of aquatic microbes (Yu et al. 2014), and nonbiodegradable antibiotics also increase the selective pressure for the transfer and mutations of antibiotics resistance genes in the whole water cycle (Zhao et al. 2019), weakening the antibacterial action of antibiotics and threatening ecological safety (Hao et al. 2015). Thus, in addition to advanced techniques coupled to conventional treatment processes (Moreira et al. 2016, Li et al. 2014), novel methods should be developed to promote antibiotics degradation in wastewater treatment plants (WWTPs).

Researchers found free nitrous acid (FNA), the protonated form of nitrite (Jiang et al. 2011), can react with pollutants such as sulfide (Jiang et al. 2013a), catechols (Khalafi et al. 2010), and phenols (Ridd et al. 1991) via direct hydroxylation, deamination, and nitrosubstitution (Sun et al. 2019). In recent years, the FNA-based technologies have been broadly developed in wastewater management to obtain effects such as controlling corrosion and odor in sewers, achieving carbon and energy-efficient nitrogen removal during wastewater treatment, and improving waste activated sludge reduction and energy recovery (Duan et al. 2020). Sun et al. found that FNA interfered with sulfamethoxazole degradation in the nitrification process but did not fully evaluate the chemical efficacy of FNA for antibiotics because the low FNA concentration (0.04 mg-N/L) presented a limited sulfamethoxazole removal of 6-16% (Sun et al. 2019). In fact, a large amount of FNA can be accumulated during the nitritation of anaerobic digestion liquor, source-separated urine, and landfill leachate (Zheng et al. 2017, Law et al. 2015). However, the chemical efficacy and the underlying mechanism of the effect of high FNA concentrations on antibiotics are still unclear. Thus, it is essential to investigate the optimal reaction conditions, develop a kinetics model, analyze the reaction pathway, and evaluate the toxicity of byproducts to obtain a deeper understanding of FNA-based elimination on antibiotics.

Generally, aromatic amines readily react with nitric oxide (NO) to form diazonium cations (Brückner 2004), and the unstable diazonium cations undergo consecutive reactions to form aromatic nitro-(NO₂) species in the presence of excess nitrite (Nödler et al. 2012, Itoh et al. 1996). In addition, it is reported that the derivatives of FNA, i.e., NO, N₂O₃, NO₂ and N₂O₄, and the reactive nitrogen intermediates, i.e., ·NO and ·NO₂, are hypothesized to intervene with pollutants transformation (Jiang and Yuan 2013b, Park and Lee 1988). The chemical degradation pathway of antibiotics exposed to FNA is not determined. Thus, the potential pathways should be inferred according to detectable abundant products.

Currently, toxicological evaluation of degradation products is recommended if the transformation products become more or less biologically active than the original chemicals. A previous study showed that the transformation products obtained via UV/PDS oxidation treatment were more toxic than the parent forms (Zhang et al. 2016), whereas the toxicity of the products obtained by FNA chemical treatment is unknown. In addition, since the antibacterial activity of sulfonamides originates from the sulfanilamide toxicophore structure of the sulfonamide group bound to aniline in the para position (Majewsky et al. 2014), the changes of antibacterial activity upon the change of partial functional moieties are unknown. Thus, it is essential to evaluate the biological toxicity and antibacterial properties of the antibiotics byproducts.

In this work, sulfamethoxazole (SMX) is selected as the target micropollutant due to its heavy consumption, frequent detection and widespread distribution in natural waters. A comprehensive evaluation of FNA-based elimination of SMX is conducted, including specific elimination identification, kinetics construction, transformation pathways inference, and toxicity and antibacterial property evaluation. The present study is the first to provide a comprehensive understanding of FNA-based technology for antibiotics control.