Radical fluorine transfer catalysed by an engineered nonheme iron enzyme.

Nonheme iron enzymes stand out as one of the most versatile biocatalysts for molecular functionalization. They facilitate a wide array of chemical transformations within biological processes, including hydroxylation, chlorination, epimerization, desaturation, cyclization, and more. Beyond their native biological functions, these enzymes possess substantial potential as powerful biocatalytic platforms for achieving abiological metal-catalyzed reactions, owing to their functional and structural diversity and high evolvability. To this end, our group has recently engineered a series of nonheme iron enzymes to employ non-natural radical-relay mechanisms for abiological radical transformations not previously known in biology. Notably, we have demonstrated that a nonheme iron enzyme, (S)-2-hydroxypropylphosphonate epoxidase from Streptomyces viridochromogenes (SvHppE), can be repurposed into an efficient and selective biocatalyst for radical fluorine transfer reactions. This marks the first known instance of a redox enzymatic process for C(sp3)F bond formation. This chapter outlines the detailed experimental protocol for engineering SvHPPE for fluorination reactions. Furthermore, the provided protocol could serve as a general guideline that might facilitate other engineering endeavors targeting nonheme iron enzymes for novel catalytic functions.

Fluorination of porphyrin ß-periphery boosts nickel(II)-catalyzed hydrogen evolution reaction.

Tunichlorin, the naturally occurring chlorophyll cofactor containing Ni(II) ion, sets up a golden standard for designing the electrocatalysts for hydrogen evolution reaction (HER) via ß-peripheral modification. Besides the fine-tuning of the porphyrin ß-periphery such as adjusting the aromatics (the saturated level of tetrapyrrole) or installing hydroxyl group (hydrogen bond network) to enhance the catalytic HER efficiency, here we report that ß-fluorination of porphyrin is also an important approach to increase the reactivity of Ni(II) center. Benefiting the previously reported derivatization of ß-fluorinated porpholactones, we constructed a ß-fluorinated tunichlorin mimic (6). Compared with the non-fluorinated analogs (1, 3, and 5), we found that 2, 4, and 6 exhibit significant electrocatalytic HER reactivity acceleration (in terms of turnover frequencies, TOF, s-1) of ca. 37, 170, 133-fold, respectively. Mechanism studies suggested that ß-fluorination negatively shifts the metal complexes' reduction potentials and accelerates the electron transfer process, both contributing to the boosting of HER reaction. Notably, 6 showed an 890-fold increase of TOFs than 1, demonstrating the combining advantages of the of fluorination, hydrogenation, and hydroxylation at porphyrin ß-periphery.

Expeditious Synthesis of Gwanakoside A and the Chloronaphthol Glycoside Congeners.

The synthesis of gwanakoside A, a chlorinated naphthol bis-glycoside, and its analogues was achieved through stepwise chlorination and donor-equivalent controlled regioselective phenol glycosylation with glycosyl N-phenyltrifluoroacetimidates as donors. Gwanakoside A displayed considerable inhibitory effects against various cancer cells and Staphylococcus aureus strains.

Identification of reaction sites and chlorinated products of purine bases and nucleosides during chlorination: a computational study.

Hypochlorous acid (HOCl) released from activated leukocytes plays a significant role in the human immune system, but is also implicated in numerous diseases due to its inappropriate production. Chlorinated nucleobases induce genetic changes that potentially enable and stimulate carcinogenesis, and thus have attracted considerable attention. However, their multiple halogenation sites pose challenges to identify them. As a good complement to experiments, quantum chemical computation was used to uncover chlorination sites and chlorinated products in this study. The results indicate that anion salt forms of all purine compounds play significant roles in chlorination except for adenosine. The kinetic reactivity order of all reaction sites in terms of the estimated apparent rate constant kobs-est (in M-1 s-1) is heterocyclic NH/N (102-107) > exocyclic NH2 (10-2-10) > heterocyclic C8 (10-5-10-1), but the order is reversed for thermodynamics. Combining kinetics and thermodynamics, the numerical simulation results show that N9 is the most reactive site for purine bases to form the main initial chlorinated product, while for purine nucleosides N1 and exocyclic N2/N6 are the most reactive sites to produce the main products controlled by kinetics and thermodynamics, respectively, and C8 is a possible site to generate the minor product. The formation mechanisms of biomarker 8-Cl- and 8-oxo-purine derivatives were also investigated. Additionally, the structure-kinetic reactivity relationship study reveals a good correlation between lg kobs-est and APT charge in all purine compounds compared to FED2 (HOMO), which proves again that the electrostatic interaction plays a key role. The results are helpful to further understand the reactivity of various reaction sites in aromatic compounds during chlorination.

Fluorination of a conserved tyrosine in POR offers new clues for proton transfer.

Reduction of the 17,18-double bond in the D-ring during chlorophyll biosynthesis is catalyzed by the rare, naturally occurring photoenzyme protochlorophyllide oxidoreductase (POR). A conserved tyrosine residue has been suggested to donate a proton to C18 of the substrate in the past decades. Taylor and colleagues scrutinized the model with a powerful tool that utilized a modified genetic code to introduce fluorinated tyrosine analogues into POR. The presented results show that the suggested catalytically critical tyrosine is unlikely to participate in the reaction chemistry but is required for substrate binding, and instead, a cysteine residue preceding the lid helix is proposed to have the role of proton donor.

The influence of backbone fluorination on the helicity of α/γ-hybrid peptides.

Peptides that are composed of an alternating pattern of α- and γ-amino acids are potentially valuable as metabolism-resistant bioactive agents. For optimal function, some kind of conformational restriction is usually required to either stabilize the dominant 12-helix, or else to divert the peptide away from this conformation in a controlled way. Herein, we explore stereoselective fluorination as a method for controlling the conformations of α/γ-hybrid peptides. We show through a combination of X-ray, NMR and CD analyses that fluorination can either stabilize or disrupt the 12-helix, depending on the fluorine stereochemistry. These findings could inform the ongoing development of diverse functional hybrid peptides.

Copper ion affects oxidant decay and combined aspartic acid transformation during chlorination in water pipes: Differentiated action on the yield of trihalomethanes and haloacetonitriles.

The chlorination of extracellular polymeric substances (EPS) secreted by biofilm often induces the formation of high-toxic disinfection byproducts (DBPs) in drinking water distribution systems. The protein components in EPS are the main precursors of DBPs, which mostly exist in the form of combined amino acids. The paper aimed to study the action of a pipe corrosion product (Cu2+) on the formation of DBPs (trihalomethanes, THMs; haloacetonitriles, HANs) with aspartic acid tetrapeptide (TAsp) as a precursor. Cu2+ mainly promoted the reaction of oxidants with TAsp (i.e., TAsp-induced decay) to produce DBPs, rather than self-decay of oxidants to generate BrO3‒ and ClO3‒. Cu2+ increased THMs yield, but decreased HANs yield due to the catalytic hydrolysis. Cu2+ was more prone to promote the reaction of TAsp with HOCl than with HOBr, leading to a DBPs shift from brominated to chlorinated species. The chemical characterizations of Cu2+-TAsp complexations demonstrate that Cu2+ combined with TAsp at the N and O sites in both amine and amide groups, and the intermediate identification suggests that Cu2+ enhanced the stepwise chlorination process by promoting the substitution of chlorine and the breakage of CC bonds. The effect of Cu2+ on THMs yield changed from promoting to inhibiting with the increase of pH, while that on HANs yield was inhibiting regardless of pH variation. Additionally, the impact of Cu2+ on the formation of DBPs was also affected by Cu2+ dose, Cl2/C ratio and Br- concentration. This study helps to understand the formation of EPS-derived DBPs in water pipes, and provides reference for formulating control strategies during biofilm outbreaks.

Structural and functional insights into the self-sufficient flavin-dependent halogenase.

Flavin-dependent halogenases (FDHs) have tremendous applications in synthetic chemistry. A single-component FDH, AetF, exhibits both halogenase and reductase activities in a continuous polypeptide chain. AetF exhibits broad substrate promiscuity and catalyzes the two-step bromination of l-tryptophan (l-Trp) to produce 5-bromotryptophan (5-Br-Trp) and 5,7-dibromo-l-tryptophan (5,7-di-Br-Trp). To elucidate the mechanism of action of AetF, we solved its crystal structure in complex with FAD, FAD/NADP+, FAD/l-Trp, and FAD/5-Br-Trp at resolutions of 1.92-2.23 Å. The obtained crystal structures depict the unprecedented topology of single-component FDH. Structural analysis revealed that the substrate flexibility and dibromination capability of AetF could be attributed to its spacious substrate-binding pocket. In addition, highly-regulated interaction networks between the substrate-recognizing residues and 5-Br-Trp are crucial for the dibromination activity of AetF. Several Ala variants underwent monobromination with >98 % C5-regioselectivity toward l-Trp. These results reveal the catalytic mechanism of single-component FDH for the first time and contribute to efficient FDH protein engineering for biocatalytic halogenation.

Using machine learning to trace the pollution sources of disinfection by-products precursors compared to receptor models.

To increase the efficiency of managing backup water resources, it is critical to identify and allocate pollution sources. Source apportionment of dissolved organic matter (DOM) was investigated in our work. Parallel factor analysis (PARAFAC) and the Spearman correlation analysis were used for source identification. After that, a newly hybrid model applying the fuzzy c-means and support vector regression (FCM-SVR) was employed for source apportionment compared to receptor models. The results demonstrated that the FCM-SVR model exhibited excellent generalization, and only required standardization and normalization as pre-processing steps for dataset. According to the results, microbial sources played a key role (28.1 %) in the formation potential of disinfection byproducts (DBPFPs). Additionally, shipping marine sources exhibited a substantial contribution (21.2 %) to DBPFPs. The prediction accuracy of DBPFPs was matched or exceeded receptor models, and the R2 of DOC (0.884) was significantly high. Therefore, we recommend the FCM-SVR model combined with PARAFAC to trace the source of DBPFPs as its significant effectiveness in source identification, source apportionment, and prediction accuracy, possessing the potential for further applicability in tracking more organic compounds. ENVIRONMENTAL IMPLICATION: The disinfection byproducts precursors in water sources, which were thought to be hazardous materials in this study, are proved to be chlorinated into carcinogenic disinfection byproducts (DBPs) during drinking water treatment, However, the source apportionment methods of DBPs are not well developed compared to other inorganic matter, e.g., heavy metals and ammonia nitrogen. We proposed a new FCM-SVR model to trace the source of DBPs, which required easier pre-treatment and resulted a better source apportionment and prediction accuracy. As a result, it could provide a different prospect and useful management advices to trace the source of DBPs.

Formation and toxicity contribution of chlorinated and dechlorinated halobenzoquinones from dichlorophenols after ozonation.

Halobenzoquinones (HBQs) are a class of disinfection byproducts with high cytotoxicity and potential carcinogenicity, which have been widely detected in chlorination of drinking water and swimming pool water. However, to date, the formation of HBQs upon ozonation and the HBQ precursors have been overlooked. This study investigated the formation of chlorinated and dechlorinated HBQs from six dichlorophenol (DCP) isomers. The monomeric and dimeric HBQs were identified in all the ozonation effluents, exhibiting 1-100 times higher toxicity levels than their precursors. The sum of detected HBQs intensity had a satisfactory linear relation with the maximum toxic unit (R2 = 0.9657), indicating the primary toxicity contribution to the increased overall toxicity of effluents. Based on density functional theory calculations, when ozone attacks the para carbon to the hydroxyl group of 2,3-DCP, the probability of producing chlorinated HBQs is 80.41 %, indicating that the para carbon attack mainly resulted in the formation of monomeric HBQs. 2,3-dichlorophenoxy radicals were successfully detected in ozonated 2,3-DCP effluent through electron paramagnetic resonance and further validated using theoretical calculation, revealing the formation pathway of dimeric HBQs. The results indicate that chlorinated phenols, regardless of the positions of chlorine substitution, can potentially serve as precursors for both chlorinated and dechlorinated HBQs formation during ozonation.

Network Toxicology Prediction and Molecular Docking-based Strategy to Explore the Potential Toxicity Mechanism of Metformin Chlorination Byproducts in Drinking Water.

BACKGROUND: Metformin (MET), a worldwide used drug for treating type 2 diabetes but not metabolized by humans, has been found with the largest amount in the aquatic environment. Two MET chlorination byproducts, including Y and C, were transformed into drinking water during chlorination. However, the potential toxicity of the byproducts in hepatotoxicity and reproduction toxicity remains unclear. METHODS: The TOPKAT database predicted the toxicological properties of metformin disinfection by-products. The targets of metformin disinfection by-products were mainly obtained from the PharmMapper database, and then the targets of hepatotoxicity and reproductive toxicity were screened from GeneCards. The overlapping targets of toxic component targets and the hepatotoxicity or reproduction toxicity targets were regarded as the key targets. Then, the STRING database analyzed the key target to construct a protein-protein interaction network (PPI) and GO, and KEGG analysis was performed by the DAVID platform. Meanwhile, the PPI network and compound- target network were constructed by Cytoscape 3.9.1. Finally, Discovery Studio 2019 software was used for molecular docking verification of the two toxic compounds and the core genes. RESULTS: Y and C exhibited hepatotoxicity, carcinogenicity, and mutagenicity evaluated by TOPKAT. There were 22 potential targets relating to compound Y and hepatotoxicity and reproduction toxicity and 14 potential targets relating to compound C and hepatotoxicity and reproduction toxicity. PPI network analysis showed that SRC, MAPK14, F2, PTPN1, IL2, MMP3, HRAS, and RARA might be the key targets; the KEGG analysis indicated that compounds Y and C caused hepatotoxicity through Hepatitis B, Pathways in cancer, Chemical carcinogenesis-reactive oxygen species, Epstein-Barr virus infection; compound Y and C caused reproduction toxicity through GnRH signaling pathway, Endocrine resistance, Prostate cancer, Progesterone-mediated oocyte maturation. Molecular docking results showed that 2 compounds could fit in the binding pocket of the 7 hub genes. CONCLUSION: This study preliminarily revealed the potential toxicity and possible toxicity mechanism of metformin disinfection by-products and provided a new idea for follow-up research.

Cocamidopropyl betaine - a potential source of nitrogen-containing disinfection by-products in pool water.

Water treatment for most public pools involves disinfection with active chlorine leading to the formation of disinfection by-products (DBPs). Among them, nitrogen-containing compounds (N-DBPs) having increased toxicity and adverse effects on human health are of the greatest concern. Being the major component of various body washers for swimmers, cocamidopropyl betaine (CAPB) represents a potential and still underestimated anthropogenic precursor of N-DBPs in pool water. The purpose of this study was to investigate CAPB transformation pathways and mechanisms under the aqueous chlorination conditions. High-performance liquid and two-dimensional gas chromatography hyphenated with high-resolution mass spectrometry were used for the search and tentative identification of the primary and final CAPB transformation products. A wide range of DBPs containing up to five chlorine atoms including these in combination with hydroxyl and additional carbonyl groups has been revealed in model chlorination experiments for the first time. The proposed mechanism of their formation involves nucleophilic substitution of the secondary amide hydrogen atom at the first stage with subsequent free radical and electrophilic addition reactions resulting in non-selective introduction of halogen atoms and hydroxyl groups in the alkyl chain. The deep transformation products include short-chain chlorinated hydrocarbons and their oxidation products as well as dimethylcarbamoyl chloride possessing high toxicity and carcinogenic properties. Targeted analysis of real swimming pool water samples confirmed the results of model experiments enabling semi-quantitative determination of CAPB (0.8 µg L-1) and 18 primary DBPs, including 10 chlorine-containing compounds with the total concentration of 0.1 µg L-1. Among them, monochloro (50%) and hydroxydichloro (25%) derivatives predominate. The toxicity and health of the main DBPs has been estimated using QSAR/QSTR approach. Thus, the possibility of formation of new classes of potentially toxic chlorine-containing DBPs associated with the widespread use of detergents and cosmetics was shown.

Insight into the chemical transformation and organic release of polyurethane microplastics during chlorination.

The ubiquitous occurrence of microplastics in water and wastewater is a growing concern. In this study, the chemical transformation and organic release of virgin and UV-aged thermoplastic polyurethane (TPU) polymers during chlorination were investigated. As compared to virgin TPU polymer, the UV-aged TPU polymer exhibited high chlorine reactivity with noticeable destruction on its surface functional groups after chlorination, which could be ascribed to the UV-induced activation of hard segment of TPU backbone and increased contact area. The concentrations of leached organics increased by 1.6-fold with obviously high abundances of low-molecular-weight components. Additives, monomers, compounds relating to TPU chain extension, and their chlorination byproducts contributed to the increased organic release. Meanwhile, the formation of chloroform, haloacetic acids, trichloroacetaldehyde, and dichloroacetonitrile increased by 3.8-, 1.7-, 4.9-, and 2.4-fold, respectively. Two additives and six chlorination byproducts in leachate from chlorinated UV-aged TPU were predicted as highly toxic, e.g., butyl octyl phthalate, palmitic acid, 2,6-di-tert-butyl-1,4-benzoquinone, and chlorinated aniline. Evaluated by human hepatocarcinoma cells, the 50% lethal concentration factor of organics released from chlorinated UV-aged TPU was approximately 10% of that from its virgin counterpart, indicating a substantially increased level of cytotoxicity. This study highlights that the release of additives and chlorination byproducts from the chemical transformation of UV-aged microplastics during chlorination may be of potentially toxic concern.

Enzymatic Peptide and Protein Bromination: The BromoTrp Tag.

Bio-orthogonal reactions for modification of proteins and unprotected peptides are of high value in chemical biology. The combination of enzymatic halogenation with transition metal-catalyzed cross-coupling provides a feasible approach for the modification of proteins and unprotected peptides. By a semirational protein engineering approach, variants of the tryptophan 6-halogenase Thal were identified that enable efficient bromination of peptides with a C-terminal tryptophan residue. The substrate scope was explored using di-, tri-, and tetrapeptide arrays, leading to the identification of an optimized peptide tag we named BromoTrp tag. This tag was introduced into three model proteins. Preparative scale post-translational bromination was possible with only a single cultivation and purification step using the brominating E. coli coexpression system Brocoli. Palladium-catalyzed Suzuki-Miyaura cross-coupling of the bromoarene was achieved with Pd nanoparticle catalysts at 37 °C, highlighting the rich potential of this strategy for bio-orthogonal functionalization and conjugation.

Increasing the Stability of Flavin-Dependent Halogenases by Disulfide Engineering.

Flavin-dependent halogenases allow halogenation of electron-rich aromatic compounds under mild reaction conditions even at electronically unfavored positions with high regioselectivity. In order to expand the application of halogenases, the enzymes need to be improved in terms of stability and efficiency. A previous study with the tryptophan 6-halogenase Thal demonstrated that thermostable Thal variants tend to form dimers in solution while the wild type is present as a monomer. Based on this a dimeric Thal variant was generated that is covalently linked by disulfide bonds. Introducing two cysteine residues at the dimer interface resulted in the variant Thal CC with significantly increased thermostability (▵T50 =15.7 K) and stability over time at elevated temperature compared to the wild type. By introducing the homologous mutations into the tryptophan 5-halogenase PyrH, we were able to show that the stabilization by covalent dimerization can also be transferred to other halogenases. Moreover, it was possible to further increase the thermostability of PyrH by inserting cysteine mutations at alternative sites of the dimer interface.

Environmental fate and risk evolution of calcium channel blockers from chlorine-based disinfection to sunlit surface waters.

Organic micropollutants present in disinfected wastewater and discharged to sunlit surface waters may be transformed by multiple processes, such as chlorination due to the presence of chlorine residuals, solar irradiation as well as solar-irradiated chlorine residues. This study reports, for the first time, the multi-scenario degradation kinetics, transformation products, and risk evolution of calcium channel blockers (CCBs), a class of emerging pharmaceutical contaminants with worldwide prevalence in natural waters and wastewater. It was found that the chlorination of the studied CCBs (amlodipine (AML) and verapamil (VER)) was dominated by the reaction of HOCl with their neutral species, with second-order rate constants of 6.15×104 M-1 s-1 (AML) and 7.93×103 M-1 s-1 (VER) at pH 5.0-11.0. Bromination is much faster than chlorination, with the measured kapp,HOBr values of 2.94×105 M-1 s-1 and 6.58×103 M-1 s-1 for AML and VER, respectively, at pH 7.0. Furthermore, both CCBs would undergo photolytic attenuations with hydroxyl and carbonate radicals as the dominant reactive species in water. Notably, free chlorine mainly contributed to their abatement during the solar/chlorine treatment. Additionally, the halogen addition on the aromatic ring was observed during chlorination and bromination of the two CCBs. Cyclization was observed under solar irradiation only, while the aromatic ring was opened in the solar/chlorine system. Some products generated by the three transformation processes exhibited non-negligible risks of high biodegradation recalcitrance and toxicity, potentially threatening the aquatic environment and public health. Overall, this study elucidated the environmental fate of typical CCBs under different transformation processes to better understand the resulting ecological risks in these environmental scenarios.

Non-regulated haloaromatic water disinfection byproducts act as endocrine and lipid disrupters in human placental cells.

The disinfection of drinking water generates hundreds of disinfection byproducts (DBPs), including haloaromatic DBPs. These haloaromatic DBPs are suspected to be more toxic than haloaliphatic ones, and they are currently not regulated. This work investigates their toxicity and ability to interfere with estrogen synthesis in human placental JEG-3 cells, and their genotoxic potential in human alveolar A549 cells. Among the haloaromatic DBPs studied, halobenzoquinones (2,6-dichloro-1,4-benzoquinone (DCBQ) and 2,6-dibromo-1,4-benzoquinone (DBBQ)) showed the highest cytotoxicity (EC50: 18-26 µg/mL). They induced the generation of very high levels of reactive oxygen species (ROS) and up-regulated the expression of genes involved in estrogen synthesis (cyp19a1, hsd17b1). Increased ROS was linked to significant depletion of polyunsaturated lipid species from inner cell membranes. The other DBPs tested showed low or no significant cytotoxicity (EC50 ≥ 100 µg/mL), while 2,4,6-trichloro-phenol (TCP), 2,4,6-tribromo-phenol (TBP) and 3,5-dibromo-4-hydroxybenzaldehyde (DCHB) induced the formation of micronuclei at concentrations much higher than those typically found in water (100 µg/mL). This study reveals the different modes of action of haloaromatic DBPs, and highlights the toxic potential of halobenzoquinones, which had a significant impact on the expression of placenta steroid metabolism related genes and induce oxidative stress, implying potential adverse health effects.

Chlorination of Emerging Contaminants for Application in Potable Wastewater Reuse: Disinfection Byproduct Formation, Estrogen Activity, and Cytotoxicity.

With increasing water scarcity, many utilities are considering the potable reuse of wastewater as a source of drinking water. However, not all chemicals are removed in conventional wastewater treatment, and disinfection byproducts (DBPs) can form from these contaminants when disinfectants are applied during or after reuse treatment, especially if applied upstream of advanced treatment processes to control biofouling. We investigated the chlorination of seven priority emerging contaminants (17ß-estradiol, estrone, 17α-ethinylestradiol, bisphenol A (BPA), diclofenac, p-nonylphenol, and triclosan) in ultrapure water, and we also investigated the impact of chlorination on real samples from different treatment stages of an advanced reuse plant to evaluate the role of chlorination on the associated cytotoxicity and estrogenicity. Many DBPs were tentatively identified via liquid chromatography (LC)- and gas chromatography (GC)-high resolution mass spectrometry, including 28 not previously reported. These encompassed chlorinated, brominated, and oxidized analogs of the parent compounds as well as smaller halogenated molecules. Chlorinated BPA was the least cytotoxic of the DBPs formed but was highly estrogenic, whereas chlorinated hormones were highly cytotoxic. Estrogenicity decreased by ∼4-6 orders of magnitude for 17ß-estradiol and estrone following chlorination but increased 2 orders of magnitude for diclofenac. Estrogenicity of chlorinated BPA and p-nonylphenol were ∼50% of the natural/synthetic hormones. Potential seasonal differences in estrogen activity of unreacted vs reacted advanced wastewater treatment field samples were observed.

Adsorption, boiling or membrane filtration for disinfection by-product removal: How to make our drinking water safer?

Disinfection by-products (DBPs) generated in drinking water have become a global concern due to their potential harm to human health. Nevertheless, there are few studies about different point-of-use water treatments in household drinking water. The study aims to compare the effectiveness of three point-of-use water treatments: adsorption, boiling, and membrane filtration. The experimental results showed that the initial average concentration of volatile DBPs and non-volatile DBPs for tap water were 63.71 µg/L and 6.33 µg/L. The removal efficiency of DBPs for adsorption which were 75.6 % (the filter volumes from 0 L to 20 L) and 45.4 % (the filter volumes from 20 L to 50 L) during the service life of the filter element (50 L). Boiling had a high removal efficiency for volatile DBPs like trihalomethanes (THMs), haloacetaldehydes (HALs), haloacetonitriles (HANs), and haloketones (HKs) (90.5 %, 100 %, 100 %, and 100 %, respectively). However, boiling had a low removal efficiency which was 15 % in removing non-volatile DBPs like haloacetic acids (HAAs). Membrane filtration had a middle removal efficiency for THMs, HAAs, HALs, HKs, and HANs (45.3 %, 75.2 %, 46.5 %, 47.6 %, and 100 %, respectively). Through analysis of the correlation between dissolved organic matter (DOM) removal efficacy and DBP removal efficiency, it was found that the strongest correlation was observed between UV254 and DBP removal efficiency. Boiling showed a lower estimated cytotoxicity of DBPs compared to adsorption and membrane filtration. Cancer risk assessment of DBPs was below the specified risk range for three point-of-use water treatments. This study provides a reference for choosing point-of-use water treatments in household drinking water.

Trihalomethanes in developed and developing countries.

The reactions between natural organic matter, anthropogenic contaminants, ions, and disinfectants lead to the formation of disinfection by-products (DBPs) such as trihalomethanes (THMs) in drinking water. The formation of THMs is strongly related to the chlorination of water. The study's central objective was to compare the concentration of THMs in twenty developed and developing countries and their disinfection techniques. The THM concentration in 11 developed and 9 developing countries ranged from 0.5 µg/L (Germany) to 215 µg/L (Russia) and 3 µg/L (China) to 439.2 µg/L (Bangladesh), respectively. The developed country has partially succeeded in reducing THM concentration in drinking water, whereas significant steps are needed in developing countries to reduce the existing high THM concentration. The concentration of THMs in water varies among these countries because of the different water sources, water quality, environmental conditions, and efficiency of water treatment technologies. A meaningful relationship has been observed between the properties of water and the THM formation. The use of chemical disinfectants will result in new forms of DBPs that are undesirable due to their carcinogenic and mutagenic effects on human health. The DBP guidelines by various national and international agencies have helped to control and manage the THM concentration in drinking water. However, these regulatory standards are not continuously monitored. Therefore, the formation of these compounds should be prevented either by removing THMs forming precursors or by using an integrated approach for controlling THM formation by implementing advanced water treatment technology. Extensive research is desirable in domains like THM minimization strategies which are easy to deploy, scalable, and cost-effective.