Novel quinazoline-based dual EGFR/c-Met inhibitors overcoming drug resistance for the treatment of NSCLC: Design, synthesis and anti-tumor activity.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have demonstrated the ability to impede tumor cell proliferation by suppressing EGFR expression. Nonetheless, patients undergoing treatment may acquire resistance, which may occur through an EGFR-dependent (such as T790M mutation) or an EGFR-independent (such as c-Met amplification) manner. Therefore, developing dual-target inhibitors might present a potential avenue for addressing treatment-acquired resistance in patients. Herein, we designed, synthesized, and screened several novel 4-phenoxyquinazoline derivatives, aiming to identify a potent dual EGFR/c-Met inhibitor for the treatment of NSCLC, among which H-22 emerged as the most promising candidate exhibiting significant antitumor properties. Moreover, we assessed the in vitro inhibitory effect of H-22 on EGFR kinase and c-Met kinase in five cancer cell lines. In addition, a series of functional experiments (cell cycle, apoptosis assays, in vitro/in vivo animal model, etc.) were conducted to further investigate the anti-tumor mechanisms of H-22. The present study revealed that H-22 exhibited strong antitumor activity both in vitro and in vivo. Interestingly, H-22 exhibited anti-proliferative activity (2.27-3.35 µM) similar to Afatinib against all five cancer cells, with inhibitory functions against EGFRWT, EGFRL858R/T790M, and c-Met kinases at a concentration of 64.8, 305.4 and 137.4 nM, respectively. Cell cycle analysis indicated that the antiproliferative activity of H-22 was associated with its ability to cause G2/M arrest. Furthermore, in vivo data showed that H-22 could inhibit tumor growth in our xenograft models and induce apoptosis. Collectively, our findings uncovered that H-22 is a novel dual EGFR and c-Met inhibitor and a prospective anti-tumor therapeutic drug.

Discovery of novel 4-arylamino-quinazoline derivatives as EGFRL858R/T790M inhibitors with the potential to inhibit the non-small cell lung cancers.

Three series of quinazoline derivatives (7a-j, 8a-o, 9a-l) were designed and synthesized as EGFRL858R/T790M inhibitors. Series 7a-j and 8a-o are urea and thiourea derivatives while category 9a-l contain the Michael receptor active warhead. Most of the compounds exhibited excellent anti-proliferative activity in vitro against several cancer cell lines, including non-small cell lung cancer (NSCLC) cell lines A549 and H1975, among which 14 compounds had strong antiproliferative activity against A549 and H1975 cancer cells. What's more, they also showed moderate to excellent kinase inhibitory activity against EGFRWT and EGFRL858R/T790M. 8o exhibited the best kinase inhibitory activity with IC50 values of 0.8, 2.7 nM against EGFRWT and EGFRL858R/T790M, respectively. Moreover, AO single staining and Annexin V-FITC/PI staining results also indicated that both 8o and 9b significantly induced apoptosis in A549 cells. 8o arrested the cell cycle at S phase and 9b arrested the cell cycle at G1 phase.

Exploration of reaction rates of chlorine dioxide with tryptophan residue in oligopeptides and proteins.

Chlorine dioxide (ClO2), an alternative disinfectant to chlorine, has a superior ability to inactivate microorganisms, in which protein damage has been considered as the main inactivation mechanism. However, the reactivity of ClO2 with amino acid residues in oligopeptides and proteins remains poorly investigated. In this research, we studied the reaction rate constants of ClO2 with tryptophan residues in five heptapeptides and four proteins using stopped-flow or competition kinetic method. Each heptapeptide and protein contain only one tryptophan residue and the reactivity of tryptophan residue with ClO2 was lower than that of free tryptophan (3.88 × 104 (mol/L)-1sec-1 at pH 7.0). The neighboring amino acid residues affected the reaction rates through promoting inter-peptide aggregation, changing electron density, shifting pKa values or inducing electron transfer via redox reactions. A single amino acid residue difference in oligopeptides can make the reaction rate constants differ by over 60% (e.g. 3.01 × 104 (mol/L)-1sec-1 for DDDWNDD and 1.85 × 104 (mol/L)-1sec-1 for DDDWDDD at pH 7.0 (D: aspartic acid, W: tryptophan, N: asparagine)). The reaction rates of tryptophan-containing oligopeptides were also highly pH-dependent with higher reactivity for deprotonated tryptophan than the neutral specie. Tryptophan residues in proteins spanned a 4-fold range reactivity toward ClO2 (i.e. 0.84 × 104 (mol/L)-1sec-1 for ribonuclease T1 and 3.21 × 104 (mol/L)-1sec-1 for melittin at pH 7.0) with accessibility to the oxidant as the determinating factor. The local environment surrounding the tryptophan residue in proteins can also accelerate the reaction rates by increasing the electron density of the indole ring of tryptophan or inhibit the reaction rates by inducing electron transfer reactions. The results are of significance in advancing understanding of ClO2 oxidative reactions with proteins and microbial inactivation mechanisms.

Role of Chlorine Dioxide in N-Nitrosodimethylamine Formation from Oxidation of Model Amines.

N-Nitrosodimethylamine (NDMA) is an emerging disinfection byproduct, and we show that use of chlorine dioxide (ClO2) has the potential to increase NDMA formation in waters containing precursors with hydrazine moieties. NDMA formation was measured after oxidation of 13 amines by monochloramine and ClO2 and pretreatment with ClO2 followed by postmonochloramination. Daminozide, a plant growth regulator, was found to yield 5.01 ± 0.96% NDMA upon reaction with ClO2, although no NDMA was recorded during chloramination. The reaction rate was estimated to be ∼0.0085 s(-1), and on the basis of our identification by mass spectrometry of the intermediates, the reaction likely proceeds via the hydrolytic release of unsymmetrical dimethylhydrazine (UDMH), with the hydrazine structure a key intermediate in NDMA formation. The presence of UDMH was confirmed by gas chromatography-mass spectrometry analysis. For 10 of the 13 compounds, ClO2 preoxidation reduced NDMA yields compared with monochloramination alone, which is explained by our measured release of dimethylamine. This work shows potential preoxidation strategies to control NDMA formation may not impact all organic precursors uniformly, so differences might be source specific depending upon the occurrence of different precursors in source waters. For example, daminozide is a plant regulator, so drinking water that is heavily influenced by upstream agricultural runoff could be at risk.

A bibliometric perspective on the occurrence and migration of microplastics in soils amended with sewage sludge.

The land application of sewage sludge from wastewater treatment plants has been recognized as a major source of microplastic contamination in soil. Nevertheless, the fate and behavior of microplastics in soil remain uncertain, particularly their distribution and transport, which are poorly understood. This study does a bibliometric analysis and visualization of relevant research publications using the CiteSpace software. It explores the limited research available on the topic, highlighting the potential for it to emerge as a research hotspot in the future. Chinese researchers and institutions are paying great attention to this field and are promoting close academic cooperation among international organizations. Current research hot topics mainly involve microplastic pollution caused by the land application of sewage sludge, as well as the detection, environmental fate, and removal of microplastics in soil. The presence of microplastics in sludge, typically ranging from tens of thousands to hundreds of thousands of particles (p)/kg, inevitably leads to their introduction into soil upon land application. In China, the estimated annual accumulation of microplastics in the soil due to sludge use is approximately 1.7 × 1013 p. In European countries, the accumulation ranges from 8.6 to 71 × 1013 p. Sludge application has significantly elevated soil microplastic concentrations, with higher application rates and frequencies resulting in up to several-fold increases. The primary forms of microplastics found in soils treated with sludge are fragments and fibers, primarily in white color. These microplastics consist primarily of components such as polyamide, polyethylene, and polypropylene. The vertical transport behavior of microplastics is influenced by factors such as tillage, wind, rainfall, bioturbation, microplastic characteristics (e.g., fraction, particle size, and shape), and soil physicochemical properties (e.g., organic matter, porosity, electrical conductivity, and pH). Research indicates that microplastics can penetrate up to 90 cm into the soil profile and persist for decades. Microplastics in sewage sludge-amended soils pose potential long-term threats to soil ecosystems and even human health. Future research should focus on expanding the theoretical understanding of microplastic behavior in these soils, enabling the development of comprehensive risk assessments and informed decision-making for sludge management practices. PRACTITIONER POINTS: Microplastics in sewage sludge range from tens to hundreds of thousands per kilogram. Sludge land application contributes significantly to soil microplastic pollution. The main forms of microplastics in sludge-amended soils are fragments and fibers. Microplastics are mainly composed of polyamide, polyethylene, and polypropylene. Microplastics can penetrate up to 90 cm into the soil profile and persist for decades.

Biomimetic cytotoxicity control of select nitrogenous disinfection byproducts in water.

Nitrogenous disinfection byproducts (N-DBPs) in water are carcinogenic, teratogenic, and mutagenic. In this work, we developed a biomimetic reduction approach based on the cysteine thiol that destructed the highly toxic, select nitrogenous haloacetamides (HAMs) and haloacetonitriles (HANs) while effectively controlling the cytotoxicity of the degradation products to serve as a basis for further technological applications (e.g. immobilized contact bed for terminal users). Mechanisms on toxicity control were elucidated. Results showed the degradation and cytotoxicity control of HAMs as more efficient than that of the HANs. The cytotoxicity of the chlorinated, brominated, and iodinated HAMs and HANs was reduced to 25 %- 0.25 % of the original after biomimetic reduction using a reasonable concentration ratio. Through a combination of thiol-specific reactivity, dehalogenation, and quantitative structure-activity relationship analyses, the major toxicity control mechanisms were found to be the reductive dehalogenation of the N-DBPs. The halogenated functional groups on the N-DBPs had a more pronounced effect than the amide and nitrile groups on the cytotoxicity and detoxification effect. Patterns of toxicity interaction variations with DBPs concentrations were identified to detect possible synergistic cytotoxicity interactions under various combinations of HAMs and HANs in the presence of the cysteine thiol. Results could benefit future N-DBPs control efforts.

Depth profiles of microplastics in sediments from inland water to coast and their influential factors.

Microplastics, plastic particles with a size smaller than 5 mm, are widely observed in the global environments and pose a growing threat as they accumulate and affect the environments in numerous ways. These particles can be transported from inland water to coast and disperse from surface water to deep sediments, especially the latter, while knowledge of the hidden microplastics in sediment layers is still lacking. Understanding the characteristics and behavior of microplastics in deep sediments from inland water to coast is crucial for estimating the present and future global plastic budget from land to seas. Herein, present knowledge of microplastic sedimentation from inland water to coast is reviewed, with a focus on the physical characteristics of microplastics and environmental factors that affect sedimentation. The abundance, shape, composition, and timeline of microplastics in sediment layers in rivers, floodplains, lakes, estuaries and coastal wetlands are presented. The abundance of microplastics in sediment layers varies across sites and may exhibit opposite trends along depth, and generally the proportion of relatively small microplastics increases with depth, while less is known about the vertical trends in the shape and composition of microplastics. Timeline of microplastics is generally linked to the sedimentation rate, which varies from millimeters to centimeters per year in the reviewed studies. The spatiotemporal characteristics of microplastic sedimentation depend on the settling and erosion of microplastics, which are determined by two aspects, microplastic characteristics and environmental factors. The former aspect includes size, shape and density influenced by aggregation and biofouling, and the latter includes dynamic forces, topographic features, bioturbation and human activities. The comprehensive review of these factors highlights the needs to further quantify the characteristics of microplastic sedimentation and explore the role of these factors in microplastic sedimentation on various spatiotemporal scales.

New insights into thiamphenicol biodegradation mechanism by Sphingomonas sp. CL5.1 deciphered through metabolic and proteomic analysis.

Biological treatment is an efficient and economical process to remove thiamphenicol (TAP) residues from the environment. The discovery of TAP-degrading bacteria and the decryption of its biodegradation mechanism will be beneficial to enhance the biological removal of TAP. In this study, Sphingomonas sp. CL5.1 was found to be capable of catabolizing TAP as the sole carbon, nitrogen, and energy source. This strain could degrade 93.9% of 25 mg/L TAP in 36 h, and remove about 11.9% of the total organic carbon of TAP. A novel metabolism pathway of TAP was constructed, and the enzymes involved in TAP metabolism in strain CL5.1 were predicted via proteomic and metabolic analysis. TAP was proposed to be transformed to O-TAP via oxidation of C3-OH and DD-TAP via dehydration of C3-OH and dehydrogenation of C1-OH. A novel glucose-methanol-choline (GMC) family oxidoreductase CapO was predicted to be involved in the oxidation of C3-OH. O-TAP was supposed to be further cleaved into DCA, glycine, and PMB. Glycine might be a pivotal direct nitrogen source for strain CL5.1, and it could be involved in nitrogen metabolism through the glycine cleavage system or directly participate in the biosynthetic processes.

XS-2, a novel potent dual PI3K/mTOR inhibitor, exhibits high in vitro and in vivo anti-breast cancer activity and low toxicity with the potential to inhibit the invasion and migration of triple-negative breast cancer.

Breast cancer has become the most commonly diagnosed cancer, surpassing lung cancer, with 2.26 million new breast cancers worldwide in 2020. Hence, there is an urgent need to develop effective molecularly targeted therapeutic drugs to treat breast cancer. In this paper, we designed, synthesized and screened a novel thiophene-triazine derivative, XS-2, as a potent dual PI3K/mTOR inhibitor for the treatment of breast cancer. Also, XS-2 was found to be potentially effective against triple-negative breast cancer (TNBC) in vitro during the investigation. We evaluated the in vitro inhibitory effect of XS-2 on 10 cancer cell lines by MTT and 6 kinases to investigated its in vivo antitumor activity in MCF-7 xenograft tumor-bearing BALB/c nude mice. In addition, the in vitro/in vivo toxicity to mice was also assessed by hemolytic toxicity, H&E staining and blood biochemical analysis. In order to investigate the antitumor mechanism of XS-2, a series of experiments were carried out in vitro/in vivo animal model and molecular biological levels such as the cell cycle and the apoptosis assay, real-time PCR, western blot, docking and molecular simulations analysis, etc. What's more, wound healing assay, Transwell and Western Blot were applied to explore the ability of XS-2 to inhibit the cell invasion and migration. The results showed that XS-2 exhibited strong antitumor activity both in vitro and in vivo. The inhibitory activities of XS-2 on ten cancer cell lines were ranging from 1.07 ± 0.11 to 0.002 ± 0.001 µM, which were 1565 times better than that of the lead compound GDC-0941, inhibitory activities against PI3Kα and mTOR kinases were 291.0 and 60.8 nM, respectively. Notably, XS-2 not only showed significant in vivo antitumor activity and low toxicity, with the tumor inhibition rate of 57.0 %, but also exhibited strong inhibitory in the expression of related proteins of PI3K pathway in tumor tissues. In addition, XS-2 significantly inhibited breast cancer MCF-7 and MDA-MB-231 cells in a concentration- and time-dependent manner, and inhibited the migration and invasion ability of MDA-MB-231 and MCF-7 cells. More than that, XS-2 could inhibit the increase of the expression levels of N-cadherin and vimentin upregulated by EGF and reversed the E-cadherin expression down regulated by EGF, resulting in inhibiting EMT in MCF-7 and MDA-MB-231 cells. The results showed that XS-2 was expected to be successfully developed as a high-efficiency and low-toxicity breast cancer therapeutic drug with the potential to inhibit the invasion and migration of TNBC. This provides a new research idea for the treatment of TNBC, which is of great significance.

Chloramphenicol biodegradation by enriched bacterial consortia and isolated strain Sphingomonas sp. CL5.1: The reconstruction of a novel biodegradation pathway.

Figuring out the comprehensive metabolic mechanism of chloramphenicol (CAP) is critical to improving CAP removal in the bioremediation process. In this study, CAP biodegradation by six consortia and isolated Sphingomonas sp. CL5.1 were systematically investigated using the combination of high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, second-generation, and third-generation sequencing technologies. The CAP-degrading capability of six consortia was enhanced while CAP mineralization rate declined after long-term enrichment. The microbial community structures of six consortia were all simplified with 69%-82% decline in species richness after continuous passages for one year. The core genera of consortia CL and CH included Sphingomonas, Cupriavidus, Burkholderia, Chryseobacterium, and Pigmentiphaga, which accounted for over 98% of the total population. Sphingomonas was discovered as a new CAP degrader that could subsist on CAP as the sole carbon, nitrogen, and energy sources. Sphingomonas sp. CL5.1 was able to completely remove 120 mg/L CAP within 48 hours with a mineralization rate of 50.4%. The presence of acetate or nitrite could inhibit CAP metabolization by strain CL5.1. Four CAP metabolic pathways were constructed, including modification of the C3 hydroxyl group of CAP via acetylation, oxidization, dehydration and the bond cleavage between C1 and C2. C3 hydroxyl group dehydration and C1-C2 bond-cleavage were first reported regarding to CAP biotransformation. Strain CL5.1 played a core role in the consortia and was responsible for C3 hydroxyl oxidation, C3 dehydration, and C1-C2 bond cleavage. Genomic information of strain CL5.1 revealed the further mineralization pathways of downstream product p-nitrobenzoic acid via ortho- and meta-cleavage.

Discovery of Triazolo-pyridazine/-pyrimidine Derivatives Bearing Aromatic (Heterocycle)-Coupled Azole Units as Class II c-Met Inhibitors.

Two series of novel triazolo-pyridazine/-pyrimidine derivatives were designed, synthesized, and evaluated for their inhibitory activity against c-Met kinase, as well as three c-Met overexpressed cancer cell lines (A549, MCF-7, and HeLa) and one normal human hepatocytes cell line LO2 in vitro. The pharmacological data indicated that most of the tested compounds showed moderate cytotoxicity, and the most promising compound 12e exhibited significant cytotoxicity against A549, MCF-7, and HeLa cell lines with IC50 values of 1.06 ± 0.16, 1.23 ± 0.18, and 2.73 ± 0.33 µM, respectively. Moreover, the inhibitory activity of compound 12e against c-Met kinase (IC50 = 0.090 µM) was equal to that of Foretinib (IC50 = 0.019 µM). The result of the acridine orange (AO) single staining test demonstrated that compound 12e could remarkably induce apoptosis of A549 cells. The results of apoptosis and cycle distribution of cells showed that compound 12e could induce late apoptosis of A549 cells and stimulate A549 cells arresting in the G0/G1 phase. Structure-activity relationships (SARs), pharmacological results, and docking studies indicated that the introduction of 5-methylthiazole fragment to the five-atom moiety was beneficial for the activity. So far, the existing data indicated that compound 12e may become a potential class II c-Met inhibitor.

ClO2 pre-oxidation changes the yields and formation pathways of chloroform and chloral hydrate from phenolic precursors during chlorination.

Phenolic moieties in natural organic matter (NOM) are important precursors of disinfection by-products (DBPs). In this study, the formation of chloral hydrate from chlorination of seventeen phenolic compounds, including mono-, di- and tri-hydroxybenzenes, were evaluated and the role of chlorine dioxide (ClO2) pre-oxidation on its formation pathways was explored. Chloroform, was also evaluated for comparison. Chlorination of resorcinol exhibited the highest chloral hydrate yield (2.83 ±â€¯0.13%) followed by chlorination of 2,4,6-trichlorophenol (0.61 ±â€¯0.03%). The median of chloral hydrate yields from the tested phenolic compounds was 0.22%. ClO2 pre-oxidation reduced the yields of chloroform from phenol derivatives by 37-97%, except 4-methoxyphenol, catechol and 2,3-dihydroxyphenol. On the contrary, ClO2 pre-oxidation of di- and tri-hydroxybenzenes tended to increase chloral hydrate yields in post-chlorination. Mixed results (both increases and decreases) were observed in chloral hydrate formation from chlorination of mono-hydroxybenzenes after ClO2 pre-oxidation. The changes of their formation were dependent on ClO2 pre-oxidation time and dosages. Identification of transformation products suggested that phenolic compounds were mainly converted to unsaturated carbonyl structures by ClO2. Chlorine substituted benzoquinones and cyclopent-4-ene-1,3-diones were important transformation products after a series of ring open, decarboxylation, hydrolysis and chlorine substitution reactions. The changes in the formation yields of chloral hydrate and chloroform were governed by the difference in initial phenolic precursors and the transformation products after ClO2 pre-oxidation. ClO2 pre-oxidation in water treatment can effectively reduce chloroform formation but may have a risk of increasing chloral hydrate formation.

Chlorite formation during ClO2 oxidation of model compounds having various functional groups and humic substances.

Chlorine dioxide (ClO2) has been used as an alternative to chlorine in water purification to reduce the formation of halogenated by-products and give superior inactivation of microorganisms. However, the formation of chlorite (ClO2-) is a major consideration in the application of ClO2. In order to improve understanding in ClO2- formation kinetics and mechanisms, this study investigated the reactions of ClO2 with 30 model compounds, 10 humic substances and 2 surface waters. ClO2- yields were found to be dependent on the distribution of functional groups. ClO2 oxidation of amines, di- and tri-hydroxybenzenes at pH 7.0 had ClO2- yields >50%, while oxidation of olefins, thiols and benzoquinones had ClO2- yields <50%. ClO2- yields from humic substances depended on the ClO2 dose, pH and varied with different reaction intervals, which mirrored the behavior of the model compounds. Phenolic moieties served as dominant fast-reacting precursors (during the first 5 min of disinfection). Aromatic precursors (e.g., non-phenolic lignins or benzoquinones) contributed to ClO2- formation over longer reaction time (up to 24  h). The total antioxidant capacity (indication of the amount of electron-donating moieties) determined by the Folin-Ciocalteu method was a good indicator of ClO2-reactive precursors in waters, which correlated with the ClO2 demand of waters. Waters bearing high total antioxidant capacity tended to generate more ClO2- at equivalent ClO2 exposure, but the prediction in natural water should be conservative.

Disinfection byproducts and their toxicity in wastewater effluents treated by the mixing oxidant of ClO2/Cl2.

Mixing oxidant of chlorine dioxide (ClO2) and chlorine (Cl2) often applied in water disinfection. Two secondary wastewater effluents at different ammonium-N levels (0.1 and 1.6 mg N L-1) were treated with the mixing oxidant (ClO2/Cl2) to evaluate the formation of disinfection byproducts (DBPs) and the associated cytotoxicity of treated wastewaters. The total chlorine concentrations of ClO2 and Cl2 were maintained at 10 mg L-1 as Cl2 with varied mixing ratios of ClO2 to Cl2. The formation of 37 halogenated DBPs, including nitrogenous, brominated and iodinated analogues, and 2 inorganic DBPs (chlorite and chlorate) was examined. The sum concentrations of the halogenated DBPs were reduced remarkably with decreasing Cl2 percentages, but each individual DBP group had distinct features. The regulated trihalomethanes reduced the most when ClO2 was present in chlorination, but decreasing Cl2 percentage from 70% to 30% was not quite effective to reduce the formation of iodinated trihalomethanes, haloacetic acids and haloacetontriles in low ammonium-N wastewater. The bromine and iodine substitution factors tend to increase with decreasing Cl2 percentages, indicating that destruction of DBP precursors by ClO2 favored bromine and iodine incorporation. Additionally, decreasing Cl2 percentages in the mixing oxidant (ClO2/Cl2) was often accompanied with lower chlorate formation but higher chlorite formation. The toxicity of treated wastewaters was evaluated through two approaches: the calculated cytotoxicity based on the concentrations of detected DBPs and the experimental cytotoxicity using the Chinese hamster ovary (CHO) cells. The calculated cytotoxicity decreased with decreasing Cl2 percentages, with haloacetonitriles and haloacetaldehydes as predominate contributors. However, the experimental cytotoxicity tests showed that treatment of high ammonium-N wastewater with ClO2/Cl2 exhibited considerable higher (> 3 times) cytotoxicity potency than using single disinfectant.

Size exclusion chromatography with online ICP-MS enables molecular weight fractionation of dissolved phosphorus species in water samples.

Phosphorus (P) is an important and often limiting element in terrestrial and aquatic ecosystem. A lack of understanding of its distribution and structures in the environment limits the design of effective P mitigation and recovery approaches. Here we developed a robust method employing size exclusion chromatography (SEC) coupled to an ICP-MS to determine the molecular weight (MW) distribution of P in environmental samples. The most abundant fraction of P varied widely in different environmental samples: (i) orthophosphate was the dominant fraction (93-100%) in one lake, two aerosols and DOC isolate samples, (ii) species of 400-600 Da range were abundant (74-100%) in two surface waters, and (iii) species of 150-350 Da range were abundant in wastewater effluents. SEC-DOC of the aqueous samples using a similar SEC column showed overlapping peaks for the 400-600 Da species in two surface waters, and for >20 kDa species in the effluents, suggesting that these fractions are likely associated with organic matter. The MW resolution and performance of SEC-ICP-MS agreed well with the time integrated results obtained using conventional ultrafiltration method. Results show that SEC in combination with ICP-MS and DOC has the potential to be a powerful and easy-to-use method in identifying unknown fractions of P in the environment.

Differential UV-vis absorbance can characterize the reaction of organic matter with ClO2.

UV-vis differential spectroscopy was applied to characterize and quantify the spectral changes after ClO2 oxidation of ten humic substances, seven aromatic model compounds and four surface waters. The differential spectra of ten humic substances after ClO2 oxidation all exhibited a peak near 230 nm and a broad absorbance band with a maximum at around 316 nm. The differential spectra after ClO2 oxidation were distinguished from the one after chlorination, which was indicative of their different oxidation mechanisms. The differential spectra after ClO2 treatment were well fitted by seven Gaussian bands with maxima at about 200, 225, 240, 276, 316, 385 and 457 nm. Differential absorbance at 316 nm and 400 nm (denoted as DA316 and DA400, respectively) were found to best quantify the degradation of organic matters during ClO2 oxidation with negligible interferences from water matrixes. Oxidation of substituted functional groups on aromatic structures, rather than destruction of aromatic rings, was more responsible for chlorite formation. Spectral parameters-DA316 and DA400 showed strong correlations with ClO2 consumption and chlorite formation during ClO2 oxidation of humic substances and surface water samples. The results demonstrate that DA316 and DA400 can serve as promising indicators of chlorite formation and ClO2 consumption, which provide a practical approach for online water quality monitoring during ClO2 water purification.

Occurrence of nitrogenous and carbonaceous disinfection byproducts in drinking water distributed in Shenzhen, China.

A 12-month sampling program was conducted throughout a drinking water distribution system in Shenzhen and the data from 251 samples provide a comprehensive picture of the spatial and seasonal variability of 17 species disinfection by-products (DBPs) in a city with subtropical monsoon climate. The carbonaceous disinfection by-product (C-DBPs) included four trihalomethanes (THMs), three trihaloacetaldehydes (THAs) and two haloketones (HKs). Their median concentrations over the entire period were 19.9 µg/L, 3.4 µg/L and 1.4 µg/L, respectively. The nitrogenous DBPs (N-DBPs) monitored were four haloacetonitriles (HANs) and four haloacetamides (HAcAms). Their median levels were 2.0 µg/L and 1.5 µg/L, respectively. Low levels of brominated DBP species (bromine substitution factors ≤ 0.5) were observed. The BSF of each DBP class followed the trend: THMs ≈ DHAcAms > DHANs > THAs. All the DBP concentrations showed clear seasonal variations with the highest average concentrations in spring. Correlation analyses showed that the THMs and CH levels in Shenzhen drinking water could be used as statistical indicators of the levels of unregulated N-DBPs (0.4 < r < 0.7, p < 0.5). The results supplement the database of DBP occurrence in drinking water in China, and provide an important reference data set for DBP occurrence in cities with a subtropical monsoon climate around the world.

PPCP degradation by UV/chlorine treatment and its impact on DBP formation potential in real waters.

The ultraviolet/chlorine (UV/chlorine) water purification process was evaluated for its ability to degrade the residues of pharmaceuticals and personal care products (PPCPs) commonly found in drinking water sources. The disinfection byproducts (DBPs) formed after post-chlorination were documented. The performance of the UV/chlorine process was compared with that of the UV/hydrogen peroxide (UV/H2O2) process in treating three types of sand-filtered natural water. Except caffeine and carbamazepine residues, the UV/chlorine process was found to be 59-99% effective for feed water with a high level of dissolved organic carbon and alkalinity, and 27-92% effective for water with a high ammonia content. Both chlorine radicals and hydroxyl radicals were found to contribute to the observed PPCP degradation. The removal efficiencies of chlorine- and UV-resistant PPCPs such as carbamazepine and caffeine were 2-3 times greater than in the UV/H2O2 process in waters not enriched with ammonia. UV/chlorine treatment slightly enhanced the formation chloral hydrate (CH), haloketone (HK) and trichloronitromethane (TCNM). It reduced haloacetonitrile (HAN) formation during the post-chlorination in comparison with the UV/H2O2 process. In waters with high concentrations of ammonia, the UV/chlorine process was only 5-7% more effective than the UV/H2O2 process, and it formed slightly more THMs, HKs and TCNM along with reduced formation of CH and HAN. The UV/chlorine process is thus recommended as a good alternative to UV/H2O2 treatment for its superior PPCP removal without significantly enhancing DBP formation.

Investigation of disinfection byproducts formation in ferrate(VI) pre-oxidation of NOM and its model compounds followed by chlorination.

This study investigated the effect of disinfection by-products (DBPs) formation in pre-oxidation with ferrate(VI) (Fe(VI)O4(2-), Fe(VI)) and relationship between subsequent chlorination of Suwannee river natural organic matter (SRNOM) and eight model compounds containing moieties of alcohol, aldehyde, amines, amino acids, and phenol. The DBPs studied were trihalomethanes (THMs), chloral hydrate (CH), haloacetonitriles (HANs), and trichloronitromethane (TCNM). When the interaction of Fe(VI) and SRNOM was independently examined at pH 7.0, a decrease was seen in dissolved organic carbon and in the hydrophobic and hydrophilic fractions of NOM. With the model compounds, the results showed that Fe(VI) pre-oxidation and subsequent chlorination decreased the formation of THMs with most of the compounds except amines and glycine. The effect of Fe(VI) preoxidation on CH and HANs formation from model compounds varied and was dependent on ferrate doses. Fe(VI) pre-oxidation significantly enhanced TCNM formation, compared to without pre-oxidation, from subsequent chlorination of methylamine, dimethylamine and glycine and the formation increased with increasing doses of ferrate. Correlations of DBPs formation between SRNOM and model compounds were sought to identify the moieties involved in influencing the formation of DBPs. The generation of DBPs is described using the parent molecules and the kinetics and reaction products of Fe(VI)/chlorine oxidation.

The occurrence of disinfection by-products in municipal drinking water in China's Pearl River Delta and a multipathway cancer risk assessment.

Disinfection byproducts were measured in the finished drinking water from ten water treatment plants in three Chinese cities - Guangzhou, Foshan and Zhuhai. A total of 155 water samples were collected in 2011 and 2012. The median (range) of trihalomethane (THM) and haloacetic acid (HAA) levels were 17.7 (0.7-62.7) µg/L and 8.6 (0.3-81.3) µg/L, respectively. Chloroform, dichloroacetic acid and trichloroacetic acid were the dominant species observed in Guangzhou and Foshan water, while brominated THMs predominated in water from Zhuhai. Haloacetonitriles, haloketones, chloral hydrate and trichloronitromethane were usually detected at levels ranging from unquantifiable (<0.2µg/L) to 12.2µg/L (choral hydrate). THMs and HAAs showed clear seasonal variations with the total concentrations higher in winter than in summer. Correlations among DBP levels varied, with the strongest linear correlation observed between chloroform and chloral hydrate levels (R(2)=0.77). The risk of cancer from ingestion, inhalation and dermal contact exposure to THMs was estimated. CHCl2Br contributed the highest percentage of the cancer risk from ingestion pathway and CHCl3 contributed the highest of cancer risk from inhalation pathway.