Comparative analysis of chlorine-resistant bacteria after chlorination and chloramination in drinking water treatment plants.

Chlorine-resistant bacteria (CRB) in drinking water treatment plants (DWTPs) jeopardize water quality and pose a potential risk to human health. However, the specific response of CRB to chlorination and chloramination remains uncharacterized. Therefore, we analyzed 16 S rRNA sequencing data from water samples before and after chlorination and chloramination taken between January and December 2020. Proteobacteria and Firmicutes dominated all finished water samples. After chloramination, Acinetobacter, Pseudomonas, Methylobacterium, Ralstonia, and Sphingomonas were the dominant CRB, whereas Ralstonia, Bacillus, Acinetobacter, Pseudomonas, and Enterococcus were prevalent after chlorination. Over 75% of the CRB e.g. Acinetobacter, Pseudomonas, Bacillus, and Enterococcus were shared between the chlorination and chloramination, involving potentially pathogens, such as Acinetobacter baumannii and Pseudomonas aeruginosa. Notably, certain genera such as Faecalibacterium, Geobacter, and Megasphaera were enriched as strong CRB after chloramination, whereas Vogesella, Flavobacterium, Thalassolituus, Pseudoalteromonas, and others were enriched after chlorination according to LEfSe analysis. The shared CRB correlated with temperature, pH, and turbidity, displaying a seasonal pattern with varying sensitivity to chlorination and chloramination in cold and warm seasons. These findings enhance our knowledge of the drinking water microbiome and microbial health risks, thus enabling better infectious disease control through enhanced disinfection strategies in DWTPs.

Biofilm formation and antioxidation were responsible for the increased resistance of N. eutropha to chloramination for drinking water treatment.

Chloramination is an effective strategy for eliminating pathogens from drinking water and repressing their regrowth in water distribution systems. However, the inevitable release of NH4+ potentially promotes nitrification and associated ammonia-oxidizing bacteria (AOB) contamination. In this study, AOB (Nitrosomona eutropha) were isolated from environmental water and treated with two disinfection stages (chloramine disinfection and chloramine residues) to investigate the occurrence mechanisms of AOB in chloramination. The results showed that N. eutropha had considerable resistance to monochloramine compared to Escherichia coli, whose inactivation rate constant was 19.4-fold lower. The higher resistance was attributed to high levels of extracellular polymer substances (EPS) in AOB, which contribute to AOB surviving disinfection and entering the distribution system. In AOB response to the chloramine residues stage, the respiratory activity of N. eutropha remained at a high level after three days of continuous exposure to high chloramine residue concentrations (0.5-1.5 mg/L). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) suggested that the mechanism of N. eutropha tolerance involved a significantly high expression of the intracellular oxidative stress-regulating (sodB, txrA) and protein-related (NE1545, NE1546) genes. Additionally, this process enhanced EPS secretion and promoted biofilm formation. Adhesion predictions based on the XDLVO theory corroborated the trend of biofilm formation. Overall, the naturally higher resistance contributed to the survival of AOB in primary disinfection; the enhanced antioxidant response of surviving N. eutropha accompanied by biofilm formation was responsible for their increased resistance to the residual chloramines.

Closing Dichloramine Decomposition Nitrogen and Oxygen Mass Balances: Relative Importance of End-Products from the Reactive Nitrogen Species Pathway.

In drinking water chloramination, monochloramine autodecomposition occurs in the presence of excess free ammonia through dichloramine, the decay of which was implicated in N-nitrosodimethylamine (NDMA) formation by (i) dichloramine hydrolysis to nitroxyl which reacts with itself to nitrous oxide (N2O), (ii) nitroxyl reaction with dissolved oxygen (DO) to peroxynitrite or mono/dichloramine to nitrogen gas (N2), and (iii) peroxynitrite reaction with total dimethylamine (TOTDMA) to NDMA or decomposition to nitrite/nitrate. Here, the yields of nitrogen and oxygen-containing end-products were quantified at pH 9 from NHCl2 decomposition at 200, 400, or 800 µeq Cl2·L-1 with and without 10 µM-N TOTDMA under ambient DO (∼500 µM-O) and, to limit peroxynitrite formation, low DO (≤40 µM-O). Without TOTDMA, the sum of free ammonia, monochloramine, dichloramine, N2, N2O, nitrite, and nitrate indicated nitrogen recoveries ±95% confidence intervals were not significantly different under ambient (90 ± 6%) and low (93 ± 7%) DO. With TOTDMA, nitrogen recoveries were less under ambient (82 ± 5%) than low (97 ± 7%) DO. Oxygen recoveries under ambient DO were 88-97%, and the so-called unidentified product of dichloramine decomposition formed at about three-fold greater concentration under ambient compared to low DO, like NDMA, consistent with a DO limitation. Unidentified product formation stemmed from peroxynitrite decomposition products reacting with mono/dichloramine. For a 2:2:1 nitrogen/oxygen/chlorine atom ratio and its estimated molar absorptivity, unidentified product inclusion with uncertainty may close oxygen recoveries and increase nitrogen recoveries to 98% (ambient DO) and 100% (low DO).

Antiplatelet Action of Chloramine Derivatives of Adenosine Phosphates and Their Chemical Activity in Relation to Sulfur-Containing Compounds.

We studied the properties of N6-chloroadenosine phosphates (ATP, ADP, and AMP chloramines) as compounds with potentially increased antiplatelet efficacy determined by their binding to the plasma membrane of platelets. Chloramine derivatives of ATP, ADP, and AMP do not differ in their optical absorption characteristics: their absorption spectra are in the range of 220-340 nm with a maximum at 264 nm. Chloramines of adenosine phosphates are characterized by high reactivity with respect to thiol compounds. In particular, the rate constants of the reaction of N6-chloroadenosine-5'-diphosphate with N-acetylcysteine, reduced glutathione, dithiothreitol, and cysteine reach 59,000, 250,000, 340,000, and 1,250,000 M-1×sec-1, respectively, and only 1.10±0.02 M-1×sec-1 with methionine. It has been found that N6-chloradenosine-5'-triphosphate is a strong inhibitor of platelet functions: it effectively suppresses ADP-induced cell aggregation (IC50 in the whole blood is 5 µM) and inhibits aggregation of preactivated platelets and induces dissociation of their aggregates.

Pre-oxidation coupled with charged covalent organic framework membranes for highly efficient removal of organic chloramines precursors in algae-containing water treatment.

Organic chloramines in water would pose both chemical and microbiological risks. It is essential to remove the precursors of organic chloramine (amino acids and decomposed peptides/proteins) to limit its formation in disinfection. In our work, nanofiltration was chosen to remove organic chloramines precursors. To solve the "trade-off" effect and low rejection of small molecules in algae organic matter, we synthesized a thin film composite (TFC) nanofiltration (NF) membrane with a crumpled polyamide (PA) layer via interfacial polymerization on polyacrylonitrile (PAN) composite support loaded with covalent organic framework (COF) nanoparticles (TpPa-SO3H). The obtained NF membrane (PA-TpPa-SO3H/PAN) increased the permeance from 10.2 to 28.2 L m-2 h-1 bar-1 and the amino acid rejection from 24% to 69% compared to the control NF membrane. The addition of TpPa-SO3H nanoparticles decreased the thickness of PA layers, increased the hydrophilicity of the membrane, and increased the transition energy barrier for amino acids transferring through the membrane, which was identified by scanning electron microscope, contact angle test, and density functional theory computations, respectively. Finally, pre-oxidation coupled with PA-TpPa-SO3H/PAN membrane nanofiltration on the limitation of organic chloramines formation was evaluated. We found that the combined application of KMnO4 pre-oxidation and PA-TpPa-SO3H/PAN membranes nanofiltration in algae-containing water treatment could minimize the formation of organic chloramines in subsequent chlorination and maintain a high flux during filtration. Our work provides an effective way for algae-containing water treatment and organic chloramines control.

Formation characteristics and acute toxicity assessment of THMs and HAcAms from DOM and its different fractions in source water during chlorination and chloramination.

The formation characteristics of trihalomethanes (THMs) and haloacetamides (HAcAms) from dissolved organic matter and its fractions were investigated during chlorine-based disinfection processes. The relationships between water quality parameters, fluorescence parameters, and the formation levels of THMs and HAcAms were analyzed. The fractions contributing most to the acute toxicity were identified. The trichloromethane (TCM) generation level (72 h) generally followed the order of Cl2 > NH2Cl > NHCl2 process. The NHCl2 process was superior to the NH2Cl process in controlling TCM formation. Hydrophobic acidic substance (HOA), hydrophobic neutral substance (HON), and hydrophilic substance (HIS) were identified as primary precursors of 2,2-dichloroacetamide and trichloroacetamide during chlorination and chloramination. The formation of TCM mainly resulted from HOA, HON and HIS fractions relatively uniformly, while HOA and HIS fractions contributed more to the formation of bromodichloromethane and dibromomonochloromethane. UV254 could be used as an alternative indicator for the amount of ΣTHMs formed during chlorination and chloramination processes. Dissolved organic nitrogen was a potential precursor of 2,2-dichloroacetamide during chlorination process. The fractions with the highest potential acute toxicity after the chlorination were water-dependent.

Bleach Emissions Interact Substantially with Surgical and KN95 Mask Surfaces.

Mask wearing and bleach disinfectants became commonplace during the COVID-19 pandemic. Bleach generates toxic species including hypochlorous acid (HOCl), chlorine (Cl2), and chloramines. Their reaction with organic species can generate additional toxic compounds. To understand interactions between masks and bleach disinfection, bleach was injected into a ventilated chamber containing a manikin with a breathing system and wearing a surgical or KN95 mask. Concentrations inside the chamber and behind the mask were measured by a chemical ionization mass spectrometer (CIMS) and a Vocus proton transfer reaction mass spectrometer (Vocus PTRMS). HOCl, Cl2, and chloramines were observed during disinfection and concentrations inside the chamber are 2-20 times greater than those behind the mask, driven by losses to the mask surface. After bleach injection, many species decay more slowly behind the mask by a factor of 0.5-0.7 as they desorb or form on the mask. Mass transfer modeling confirms the transition of the mask from a sink during disinfection to a source persisting >4 h after disinfection. Humidifying the mask increases reactive formation of chloramines, likely related to uptake of ammonia and HOCl. These experiments indicate that masks are a source of chemical exposure after cleaning events occur.

Lysine and Arginine Reactivity and Transformation Products during Peptide Chlorination.

Chlorine reactions with peptide-bound amino acids form disinfection byproducts and contribute to pathogen inactivation by degrading protein structure and function. Peptide-bound lysine and arginine are two of the seven chlorine-reactive amino acids, but their reactions with chlorine are poorly characterized. Using N-acetylated lysine and arginine as models for peptide-bound amino acids and authentic small peptides, this study demonstrated conversion of the lysine side chain to mono- and dichloramines and the arginine side chain to mono-, di-, and trichloramines in ≤0.5 h. The lysine chloramines formed lysine nitrile and lysine aldehyde at ∼6% yield over ∼1 week. The arginine chloramines formed ornithine nitrile at ∼3% yield over ∼1 week but not the corresponding aldehyde. While researchers hypothesized that the protein aggregation observed during chlorination arises from covalent Schiff base cross-links between lysine aldehyde and lysine on different proteins, no evidence for Schiff base formation was observed. The rapid formation of chloramines and their slow decay indicate that they are more relevant than the aldehydes and nitriles to byproduct formation and pathogen inactivation over timescales relevant to drinking water distribution. Previous research has indicated that lysine chloramines are cytotoxic and genotoxic to human cells. The conversion of lysine and arginine cationic side chains to neutral chloramines should alter protein structure and function and enhance protein aggregation by hydrophobic interactions, contributing to pathogen inactivation.

Microbiological risks increased by ammonia-oxidizing bacteria under global warming: The neglected issue in chloraminated drinking water distribution system.

A rising outbreak of waterborne diseases caused by global warming requires higher microbial stability in the drinking water distribution system (DWDS). Chloramine disinfection is gaining popularity in this context due to its good persistent stability and fewer disinfection byproducts. However, the microbiological risks may be significantly magnified by ammonia-oxidizing bacteria (AOB) in distribution systems during global warming, which is rarely noticed. Hence, this work mainly focuses on AOB to explore its impact on water quality biosafety in the context of global warming. Research indicates that global warming-induced high temperatures can directly or indirectly promote the growth of AOB, thus leading to nitrification. Further, its metabolites or cellular residues can be used as substrates for the growth of heterotrophic bacteria (e.g., waterborne pathogens). Thus, biofilm may be more persistent in the pipelines due to the presence of AOB. Breakpoint chlorination is usually applied to control such situations. However, switching between this strategy and chloramine disinfection would result in even more severe nitrification and other adverse effects. Based on the elevated microbiological risks in DWDS, the following aspects should be paid attention to in future research: (1) to understand the response of nitrifying bacteria to high temperatures and the possible association between AOB and pathogenic growth, (2) to reveal the mechanisms of AOB-mediated biofilm formation under high-temperature stress, and (3) to develop new technologies to prevent and control the occurrence of nitrification in drinking water distribution system.

Elevated levels of chloramines and chlorine detected near an indoor sports complex.

Chloramines (NH2Cl, NHCl2, and NCl3) are toxic compounds that can be created during the use of bleach-based disinfectants that contain hypochlorous acid (HOCl) and the hypochlorite ion (OCl-) as their active ingredients. Chloramines can then readily transfer from the aqueous-phase to the gas-phase. Atmospheric chemical ionization mass spectrometry using iodide adduct chemistry (I-CIMS) made observations across two periods (2014 and 2016) at an urban background site on the University of Leicester campus (Leicester, UK). Both monochloramine (NH2Cl) and molecular chlorine (Cl2) were detected and positively identified from calibrated mass spectra during both sampling periods and to our knowledge, this is the first detection of NH2Cl outdoors. Mixing ratios of NH2Cl reached up to 2.2 and 4.0 parts per billion by volume (ppbv), with median mixing ratios of 30 and 120 parts per trillion by volume (pptv) during the 2014 and 2016 sampling periods, respectively. Levels of Cl2 were observed to reach up to 220 and 320 pptv. Analysis of the NH2Cl and Cl2 data pointed to the same local source, a nearby indoor sports complex with a swimming pool and a cleaning product storage shed. No appreciable levels of NHCl2 and NCl3 were observed outdoors, suggesting the indoor pool was not likely to be the primary source of the observed ambient chloramines, as prior measurements made in indoor pool atmospheres indicate that NCl3 would be expected to dominate. Instead, these observations point to indoor cleaning and/or cleaning product emissions as the probable source of NH2Cl and Cl2 where the measured levels provide indirect evidence for substantial amounts transported from indoors to outdoors. Our upper estimate for total NH2Cl emissions from the University of Leicester indoor sports complexes scaled for similar sports complexes across the UK is 3.4 × 105 ± 1.1 × 105 µg h-1 and 0.0017 ± 0.00034 Gg yr-1, respectively. The Cl-equivalent emissions in HCl are only an order of magnitude less to those from hazardous waste incineration and iron and steel sinter production in the UK National Atmospheric Emissions Inventory (NAEI).

Effects of different types of nitrogen sources in water on the formation potentials of nitrogenous disinfection by-products in chloramine disinfection process based on isotope labeling.

Nitrogenous disinfection by-products (N-DBPs) raise increasing concerns because of their high genotoxicity, cytotoxicity, and carcinogenicity compared to carbonaceous disinfection by-products (C-DBPs). Nitrogen-containing disinfectants, dissolved organic nitrogen (DON), and inorganic nitrogen may all promote the formation of N-DBPs. Therefore, it is urgent to explore the dominant nitrogen source of N-DBPs under the coexistence of multiple nitrogen sources. In this study, the effects of amino acids, nitrate, ammonia, and chloramine as different types of nitrogen sources on the formation of five N-DBPs were investigated systematically, including chloroacetonitrile (CAN), dichloroacetonitrile (DCAN), bromochloroacetonitrile (BCAN), dibromoacetonitrile (DBAN) and dichloroacetamide (DCAcAm). L-Aspartic acid (L-Asp) as the organic nitrogen source showed a high potential on the formation of N-DBPs by forming acetonitrile intermediates. Ammonia as the inorganic nitrogen source consumed oxidants and changed the existing form of chloramine, thus inhibiting the formation of N-DBPs. Instead of providing nitrogen to N-DBPs, nitrate as a salt promoted the volatilization of N-DBPs, thereby reducing the detected N-DBPs. Furthermore, an isotope labeling method was applied to clearly trace the nitrogen sources of N-DBPs via GC-MS with electron ionization. 15N-chloramine, 15N-amino acid, 15N-nitrate and 15N-ammonia were selected as the corresponding isotopic nitrogen sources. The results indicated that chloramine was the major nitrogen contributor to five N-DBPs during the chloramination of L-Asp under the coexistence of multiple nitrogen sources, ranging from 61 % to 79 %. The influence of environmental factors (reaction time, pH, and bromide) on the formation of N-DBPs during chloramination was also investigated. There was competition between brominated N-DBPs and chlorinated N-DBPs in chloramination. With the increase of reaction time or bromine, the formation potentials of chlorinated N-DBPs gradually decreased, while brominated N-DBPs gradually increased. Moreover, higher pH inhibited the generation of N-DBPs.

Exploring Pathways and Mechanisms for Dichloroacetonitrile Formation from Typical Amino Compounds during UV/Chlorine Treatment.

The formation of disinfection byproducts (DBPs) during UV/chlorine treatment, especially nitrogenous DBPs, is not well understood. This study investigated the formation mechanisms for dichloroacetonitrile (DCAN) from typical amino compounds during UV/chlorine treatment. Compared to chlorination, the yields of DCAN increase by 88-240% during UV/chlorine treatment from real waters, while the yields of DCAN from amino compounds increase by 3.3-5724 times. Amino compounds with electron-withdrawing side chains show much higher DCAN formation than those with electron-donating side chains. Phenylethylamine, l- phenylalanine, and l-phenylalanyl-l-phenylalanine were selected to represent amines, amino acids, and peptides, respectively, to investigate the formation pathways for DCAN during UV/chlorine treatment. First, chlorination of amines, amino acids, and peptides rapidly forms N-chloramines via chlorine substitution. Then, UV photolysis but not radicals promotes the transformation from N-chloramines to N-chloroaldimines and then to phenylacetonitrile, with yields of 5.4, 51.0, and 19.8% from chlorinated phenylethylamine, l-phenylalanine, and l-phenylalanyl-l-phenylalanine to phenylacetonitrile, respectively. Finally, phenylacetonitrile is transformed to DCAN with conversion ratios of 14.2-25.6%, which is attributed to radical oxidation, as indicated by scavenging experiments and density functional theory calculations. This study elucidates the pathways and mechanisms for DCAN formation from typical amino compounds during UV/chlorine treatment.

Organic chloramines attenuation and disinfection by-product formation during UV, chlorination and UV/chlorine processes.

Organic chloramines (OCs) have become one of the research focuses in the field of drinking water treatment due to its limited oxidation and sterilization ability as well as potential cytotoxicity and genetic toxicity to the public. Among widespread OCs, produced by chlorinating cytosine are a typical one exists during chlorine disinfection. OCs degradation during UV, chlorination and UV/chlorine processes were systematically investigated. UV irradiation at 254 nm could effectively degrade OCs by 96.6% after 60 min, mainly because N-Cl bond had significant UV absorption at 250-280 nm leading to the generation of Cl• and HO•. Direct chlorination had poor removal of OCs with the OCs concentration increased first and then decreased as time went by. On the other hand, the removal of OCs during UV/chlorination was much higher than that during chlorination, but was worse than that during UV alone. pH had a minor effect on OCs decomposition via UV irradiation, whereas the effect was pronounced in the chlorination and UV chlorine processes. UV wavelength can affect the degradation of OCs with efficiency decreased in the order of UV 254 > UV 265 > UV 275. The total yields of disinfection by-products (DBPs) during the degradation of OCs followed UV/chlorine > UV > chlorination. CH and DCAA were the two dominant types of DBPs among detected 7 DBPs. DBPs yield followed the order of UV254 > UV265 > UV275 at pH 6.0 and 7.0. After UV 265 irradiation, DBPs yield slightly decreased by 2.4%, 3.0% and 6.6% with the pH increased from 6.0 to 9.0. The results can provide theoretical basis for effective control of OCs in drinking water.

A Novel Reagent for Radioiodine Labeling of New Chemical Entities (NCEs) and Biomolecules.

Radioiodine labeling of peptides and proteins is routinely performed by using various oxidizing agents such as Chloramine T, Iodobeads, and Iodogen reagent and radioactive iodide (I-), although some other oxidizing agents were also investigated. The main objective of the present study was to develop and test a novel reagent, inorganic monochloramine (NH2Cl), for radioiodine labeling of new chemical entities and biomolecules which is cost-effective, easy to make and handle, and is selective to label amino acids, peptides, and proteins. The data presented in this report demonstrate that the yields of the non-radioactive iodine labeling reactions using monochloramine are >70% for an amino acid (tyrosine) and a cyclic peptide (cyclo Arg-Gly-Asp-d-Tyr-Lys, cRGDyK). No evidence of the formation of N-chloro derivatives in cRGDyK was observed, suggesting that the reagent is selective in iodinating the tyrosine residue in the biomolecules. The method was successfully translated into radioiodine labeling of amino acid, a peptide, and a protein, Bovine Serum Albumin (BSA).

Radiosynthesis and in silico bioevaluation of 131 I-Sulfasalazine as a highly selective radiotracer for imaging of ulcerative colitis.

This study demonstrated the tracking of ulcerative colitis, which is considered a stressful immune disease. Although there are many ways to test for this disease including dependence on gases, dyes, and painful anal endoscopy, these treatment modalities have many disadvantages. Hence, it is the utmost need of time to discover new methods to detect this chronic immune disease and to avoid the defects of traditional methodologies. Sulfasalazine (SSD) was labeled with iodine-131 (half-life: 8 days, Energy: 971 keV) under optimum reaction conditions including the amount of reducing agent, pH factor, chloramine-T (Ch-T) amount, and incubation period. Characterization was performed using 1 H/ 13 C-NMR, ESI-MS, and HPLC (UV/ Radio) techniques. The biodistribution study was performed in normal and ulcerative mice models, and in silico molecular docking study was performed to evaluate the possible mechanism of action to target peroxisome proliferator-activated receptor gamma (PPARγ). The high radiolabeling yield of [131 I]-sulfasalazine ([131 I]-SSD) was achieved ≥90% through the direct labeling method with radioactive iodine-131 in the presence of chloramine-T (100 µg). The radiotracer [131 I]-SSD was observed to be stable in normal saline and freshly eluted serum up to 12 hr at ambient temperature (37℃ ± 2℃). The radiotracer [131 I]-SSD showed the highest uptake in the targeted organ (i.e., ulcerative colon) which was observed to be ≥75% injected dose per gram (% ID/g) organ for 24 hr postinjection (p.i). Furthermore, in silico data collected from molecular modeling analysis of SSD and [131 I]-SSD with antimicrobial protein (PDB code: 3KEG) and peroxisome proliferator-activated receptor gamma (PPARγ) (PDB code: 4XTA) showed azoreductase activity and high binding potential for PPAR-γ site, respectively. The results of biological studies obtained in this study enlighten the usefulness of radiotracer [131 I]-SSD as a potential imaging agent for ulcerative colitis.

Probing the Effects of Heterogeneous Oxidative Modifications on the Stability of Cytochrome c in Solution and in the Gas Phase.

Covalent modifications by reactive oxygen species can modulate the function and stability of proteins. Thermal unfolding experiments in solution are a standard tool for probing oxidation-induced stability changes. Complementary to such solution investigations, the stability of electrosprayed protein ions can be assessed in the gas phase by collision-induced unfolding (CIU) and ion-mobility spectrometry. A question that remains to be explored is whether oxidation-induced stability alterations in solution are mirrored by the CIU behavior of gaseous protein ions. Here, we address this question using chloramine-T-oxidized cytochrome c (CT-cyt c) as a model system. CT-cyt c comprises various proteoforms that have undergone MetO formation (+16 Da) and Lys carbonylation (LysCH2-NH2 → LysCHO, -1 Da). We found that CT-cyt c in solution was destabilized, with a ∼5 °C reduced melting temperature compared to unmodified controls. Surprisingly, CIU experiments revealed the opposite trend, i.e., a stabilization of CT-cyt c in the gas phase. To pinpoint the source of this effect, we performed proteoform-resolved CIU on CT-cyt c fractions that had been separated by cation exchange chromatography. In this way, it was possible to identify MetO formation at residue 80 as the key modification responsible for stabilization in the gas phase. Possibly, this effect is caused by newly formed contacts of the sulfoxide with aromatic residues in the protein core. Overall, our results demonstrate that oxidative modifications can affect protein stability in solution and in the gas phase very differently.

On-Demand Generation and Use in Continuous Synthesis of the Ambiphilic Nitrogen Source Chloramine.

Herein, we demonstrate the on-demand synthesis of chloramine from aqueous ammonia and sodium hypochlorite solutions, and its subsequent utilization as an ambiphilic nitrogen source in continuous-flow synthesis. Despite its advantages in cost and atom economy, chloramine has not seen widespread use in batch synthesis due to its unstable and hazardous nature. Continuous-flow chemistry, however, provides an excellent platform for generating and handling chloramine in a safe, reliable, and inexpensive manner. Unsaturated aldehydes are converted to valuable aziridines and nitriles, and thioethers are converted to sulfoxides, in moderate to good yields and exceedingly short reaction times. In this telescoped process, chloramine is generated in situ and immediately used, providing safe and efficient conditions for reaction scale-up while mitigating the issue of its decomposition over time.

Hyaluronic acid chloramide-Synthesis, chemical structure, stability and analysis of antimicrobials.

Electron-deficient chlorine covalently immobilised on an amido group of hyaluronic acid (HA) can be potentially exceptional for applications requiring biodegradable and biocompatible polymers with enhanced antibacterial or antiviral activity. This expectation is supported by the assumption that a small amount of HA chloramide (HACl) is formed in the extracellular matrix under inflammatory conditions by a reaction of endogenous HA with hypochlorous acid (HClO) generated by a myeloperoxidase/H2O2/Cl- system. HACl synthesis optimisation showed significant limitations of HClO as an oxidative agent where only lower degrees of substitution (DS) was achieved. Commercially available oxidative agents based on chlorinated isocyanuric acid were successfully tested, producing the HA chain with almost entirely chlorinated amidic groups. The structure of the final HACl was thoroughly studied using advanced 2-dimensional NMR methodologies and LC/MS. Stability of HACl at different temperatures was monitored over 12 months. Preliminary antimicrobial and antiviral tests demonstrated the potential of HACl for applications in biomedicine.

Effects of Oxidation of Human Serum Albumin on the Binding of Aripiprazole.

Aripiprazole (ARP) is one of antipsychotics and binds to human serum albumin (HSA) with a high affinity. In this study, we investigated the binding characteristics of ARP to oxidized HSA as observed in chronic disease conditions. Oxidized HSAs were prepared using chloramine-T (CT-HSA) or metal-catalyzed oxidation system (MCO-HSA) in vitro, respectively. An increase in the carbonyl content was confirmed in oxidized HSAs. From the results of circular dichroism (CD) and tryptophan fluorescence spectra, no significant structural change of oxidized HSAs was observed. These results indicate that prepared HSAs are mildly oxidized and well reflects the status of HSA during chronic diseases. However, oxidized HSAs were observed to have a significant decrease in binding to ARP. The results of the induced CD spectrum suggested that ARP bound to oxidized HSAs with a similar orientation. These results suggest that oxidation of HSA during chronic disease state significantly affected the microenvironment of the binding site for ARP and binding capacity of HSA to ARP.