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Polychlorinated dibenzo-p-dioxins (PCDDs), comprising 75 congeners, have gained considerable attention from the general public and the scientific community owing to their high toxic potential. The base-catalyzed hydrolysis of PCDDs is crucial for the assessment of their environmental persistence. Nonetheless, owing to the substantial number of congeners and low hydrolysis rates of PCDDs, conducting hydrolysis experiments proves to be exceedingly time-consuming and financially burdensome. Herein, density functional theory and transition state theory were employed to predict the base-catalyzed hydrolysis of PCDDs in aquatic environments. Findings reveal that PCDDs undergo base-catalyzed hydrolysis in aquatic environments with two competing pathways: prevailing dioxin ring-opening and reduced reactivity in the hydrolytic dechlorination pathway. The resultant minor products include hydroxylated PCDDs, which exhibit thermodynamic stability surpassing that of the principal product, chlorinated hydroxydiphenyl ethers. The half-lives (ranging from 17.10 to 1.33 × 1010 h at pH = 8) associated with the base-catalyzed hydrolysis of PCDDs dissolved in water were shorter compared to those within the water-sediment environmental system. This observation implies that hydroxide ions can protect aquatic environments from PCDD contamination. Notably, this study represents the first attempt to predict the base-catalyzed hydrolysis of PCDDs by using quantum chemical methods.

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This work assessed the effect of different hydrolysis periods on the properties of hydrogels based on 75 % w w-1 of N,N'-dimethyl acrylamide (DMAAm) and 25 % w w-1 of starch-g-(glycidyl methacrylate) (GMASt). FTIR results confirmed the conversion of ester groups into carboxylic acids and carboxylates, besides forming a keto-enol tautomer due to the peeling reaction of starch. For DMAAm, the hydrolysis mostly converted amide into carboxylate groups. The morphology, thermal stability, and the mechanical properties of the predominantly amorphous matrices (as confirmed by XRD results) did not drastically change even after 10 days of hydrolysis in alkali media. However, the thermogravimetric analysis results suggested that DMAAm partially protected GMASt from the hydrolysis. The swelling degree of the matrix increased from (10.1 ± 2.1) g g-1 to (61.9 ± 2.6) g g-1 after 1 day of hydrolysis, but no statistical differences (at 95 % of significance) were observed for the matrices hydrolyzed for longer periods, confirming that the maximum hydrolysis occurred within 24 h. The results confirmed that the hydrolysis increased the water uptake of the GMASt/DMAAm-based matrices, making appealing for uses as a water retentor for agricultural purposes.

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Isoxazoline is a nitrogen- and oxygen-containing five-membered heterocyclic scaffold with diverse biological profiles such as antimicrobial, fungicidal, anticancer, antiviral, analgesic and anti-inflammatory activity. Accordingly, the use of this peculiar structural framework in drug discovery is a successful strategy for the development of new drug candidates. Here, a chiral saccharin/isoxazoline hybrid was considered to investigate the tendency of the imine moiety of the heterocyclic ring to tautomerize to the enamine form in the presence of a basic catalyst. The pseudo-first-order rate constants for the base-catalyzed tautomerization process were measured in different solvents and at different temperatures by off-column kinetic experiments based on the amylose (3,5-dimethylphenylcarbamate)-type chiral stationary phase. The kinetic results obtained in this study may be a useful aid in the perspective of designing experimental conditions to control the stereointegrity of these types of pharmacologically active compounds and drive their synthesis toward the preferred, imine or enamine, tautomer.

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1,2,4-Oxadiazole is an essential motif in drug discovery represented in many experimental, investigational, and marketed drugs. This review covers synthetic methods that allow the conversion of different types of organic compounds into 1,2,4-oxadiazole at ambient temperature and the practical application of the latter approaches for the preparation of pharmaceutically important molecules. The discussed methods are divided into three groups. The first combines two-stage protocols requiring the preliminary preparation of O-acylamidoximes followed by cyclization under the action of organic bases. The advantages of this route are its swiftness, high efficiency of the cyclization process, and uncomplicated work-up. However, it requires the preparation and isolation of O-acylamidoximes as a separate preliminary step. The second route is a one-pot synthesis of 1,2,4-oxadiazoles directly from amidoximes and various carboxyl derivatives or aldehydes in aprotic bipolar solvents (primarily DMSO) in the presence of inorganic bases. This recently proposed pathway proved to be highly efficient in the field of medicinal chemistry. The third group of methods consists of diverse oxidative cyclizations, and these reactions have found modest application in drug design thus far. It is noteworthy that the reviewed methods allow for obtaining 1,2,4-oxadiazoles with thermosensitive functions and expand the prospects of using the oxadiazole core as an amide- or ester-like linker in the design of bioactive compounds.

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The herbicide isoxaflutole has the potential to contaminate drinking water directly, as well as upon hydrolyzing to its active form diketonitrile. Diketonitrile also may impact water quality by acting as a precursor for dichloroacetonitrile (DCAN), which is an unregulated but highly toxic disinfection byproduct (DBP). In this study, we investigated the reaction of diketonitrile with free chlorine and chloramine to form DCAN. We found that diketonitrile reacts with free chlorine within seconds but reacts with chloramine on the time scale of hours to days. In the presence of both oxidants, DCAN was generated at yields up to 100%. Diketonitrile reacted fastest with chlorine at circumneutral pH, which was consistent with base-catalyzed halogenation involving the enolate form of diketonitrile present at alkaline pH and electrophilic hypochlorous acid, which decreases in abundance above its pKa (7.5). In contrast, we found that diketonitrile reacts faster with chloramine as pH values decreased, consistent with an attack on the enolate by electrophilic protonated monochloramine that increases in abundance at acidic pH approaching its pKa (1.6). Our results indicate that increasing isoxaflutole use, particularly in light of the recent release of genetically modified isoxaflutole-tolerant crops, could result in greater occurrences of a high-yield DCAN precursor during disinfection.

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Hydrolysis plays an imperative role in the abiotic transformation process of antibiotics in aqueous solutions. However, little information is available on the hydrolysis process of spectinomycin (an aminocyclitol antibiotic). This study systematically investigated the spectinomycin hydrolysis kinetics and mechanisms under different pH via experiments and density functional theory (DFT) computation. Hydrolysis was first conducted in a pure water system under pH of 4.0-9.0 and temperature of 25 °C, 50 °C and 70 °C, respectively. Results showed that hydrolysis was highly dependent on pH and temperature. When pH > 6.0, spectinomycin hydrolysis was accelerated by the catalysis of OH-. Meanwhile, the hydrolysis rate increased with the elevation of temperature. Then, for the reference of the practical environment, the general base-catalyzed hydrolysis and mechanisms were studied under environmental pH 6.0-8.0 and 25 °C. DFT calculation demonstrated that base-catalyzed hydrolysis of spectinomycin could be more thermodynamically and kinetically favorable based on the lower Gibbs free energies of reaction and Gibbs free energies of activation. Further, instead of specific base catalysis (OH-), the general base catalysis (e.g., phosphate buffer) was also found to promote hydrolysis efficiency. The antibacterial activity and ecotoxicities of the hydrolysis product were analyzed to be lower than the precursor, thereby decreasing the environmental impact of spectinomycin.

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The oxidative decomposition/degradation of two main tea flavanols, EGCG/GCG and ECG/CG, was studied in alkaline solution under ultrasonic-assisted thermal conditions. The study employed HPLC-ESI-ToF-MS to identify the products generated by atmospheric oxygen oxidation and various base-catalyzed reactions. Strong basic condition led to accelerated hydrolysis and oxidation of EGCG/GCG and ECG/CG and yielded gallic acid, de-galloyl flavanols and corresponding o-quinone derivatives. Meanwhile, peroxidation or base-catalyzed cleavage and rearrangement occurred extensively on C- and B-rings of flavanol and generated various simpler aldehydes or acids. Besides, a number of dimers/trimers were produced. This contribution provides empirical proof of oxidative degradation of flavanols under strong alkaline condition. Meanwhile, detailed reaction mechanisms of C-/B-ring degradation and dimerization/polymerization phenomena are proposed to help understand the structural changes of flavanols under strong alkaline conditions.

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In recent decades, bicyclic nitroxyl radicals have caught chemists' attention as selective catalysts for the oxidation of alcohols and amines and as additives and mediators in directed C-H oxidative transformations. In this regard, the design and development of synthetic approaches to new functional bicyclic nitroxides is a relevant and important issue. It has been reported that imidazo[1,2-b]isoxazoles formed during the condensation of acetylacetone with 2-hydroxyaminooximes having a secondary hydroxyamino group are recyclized under mild basic catalyzed conditions to 8-hydroxy-5-methyl-3-oxo-6,8-diazabicyclo[3.2.1]-6-octenes. The latter, containing a sterically hindered cyclic N-hydroxy group, upon oxidation with lead dioxide in acetone, virtually quantitatively form stable nitroxyl bicyclic radicals of a new class, which are derivatives of both 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TEMPON) and 3-imidazolines.

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Phosphodiester bonds in the backbones of double-stranded (ds)RNA and single-stranded (ss)RNA are known to undergo alkaline hydrolysis. Consequently, dsRNA agents used in emerging RNA interference (RNAi) products have been assumed to exhibit low chemical persistence in solutions. However, the impact of the duplex structure of dsRNA on alkaline hydrolysis has not yet been evaluated. In this study, we demonstrated that dsRNA undergoes orders-of-magnitude slower alkaline hydrolysis than ssRNA. Furthermore, we observed that dsRNA remains intact for multiple months at neutral pH, challenging the assumption that dsRNA is chemically unstable. In systems enabling both enzymatic degradation and alkaline hydrolysis of dsRNA, we found that increasing pH effectively attenuated enzymatic degradation without inducing alkaline hydrolysis that was observed for ssRNA. Overall, our findings demonstrated, for the first time, that key degradation pathways of dsRNA significantly differ from those of ssRNA. Consideration of the unique properties of dsRNA will enable greater control of dsRNA stability during the application of emerging RNAi technology and more accurate assessment of its fate in environmental and biological systems, as well as provide insights into broader application areas including dsRNA isolation, detection and inactivation of dsRNA viruses, and prebiotic molecular evolution.

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Quenching agents (QAs) are widely used in order to prevent the additional formation of disinfection by-products (DBPs) during the sample holding time. In addition, DBP levels are usually stabilized by adjusting the pH of water samples. Previous studies have mostly focused on the individual effects of QAs or of pH on the stability of DBPs in water samples. Considering that disinfectant quenching and pH adjustments are applied simultaneously during routine analyses, it is more appropriate to evaluate the stability of DBPs with all the chemicals (e.g., disinfectants, QAs, buffers) present in the water. This study investigated the synergistic effects of different QAs (ascorbic acid, ammonium chloride, or no quenching) and pH adjustment (3-9) strategies on the stability of different classes of DBPs (i.e., trihalomethanes (THMs), halogenated acetaldehydes (HALs), haloacetonitriles (HANs), haloketones (HKs), and halonitromethane (HNM)). Sample preservation conditions that did not include a QA were shown to be inadequate for GC-ECD analysis, due to interference problems. Ammonium chloride was found to be effective for most DBPs. However, some HALs continued to form in the presence of chloramine, which is a by-product of dechlorination using ammonium chloride. Conversely, using ascorbic acid efficiently inactivated residual chlorine, providing a clean chromatographic baseline. Based on the results of this study, we recommend the use of ascorbic acid for quenching and sulfuric acid for acidifying (pH 3.5) samples. Considering the instability of some DBPs in water matrices over long periods (i.e., 14 days), samples should be processed as soon as possible after collection.

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BACKGROUND: Lignin is a potential feedstock for microbial conversion into various chemicals. However, the microbial degradation rate of native or technical lignin is low, and chemical depolymerization is needed to obtain reasonable conversion rates. In the current study, nine bacterial strains belonging to the Pseudomonas and Rhodococcus genera were evaluated for their ability to grow on alkaline-treated softwood lignin as a sole carbon source. RESULTS: Pseudomonas fluorescens DSM 50090 and Rhodococcus opacus DSM1069 showed the best growth of the tested species on plates with lignin. Further evaluation of P. fluorescens and R. opacus was made in liquid cultivations with depolymerized softwood Kraft lignin (DL) at a concentration of 1 g/L. Size-exclusion chromatography (SEC) showed that R. opacus consumed most of the available lower-molecular weight compounds (approximately 0.1-0.4 kDa) in the DL, but the weight distribution of larger fractions was almost unaffected. Importantly, the consumed compounds included guaiacol-one of the main monomers in the DL. SEC analysis of P. fluorescens culture broth, in contrast, did not show a large conversion of low-molecular weight compounds, and guaiacol remained unconsumed. However, a significant shift in molecular weight distribution towards lower average weights was seen after cultivation with P. fluorescens. CONCLUSIONS: Rhodococcus opacus and P. fluorescens were identified as two potential microbial candidates for the conversion/consumption of base-catalyzed depolymerized lignin, acting on low- and high-molecular weight lignin fragments, respectively. These findings will be of relevance for designing bioconversion of softwood Kraft lignin.

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Chlorine-containing organic waste (COWs) is a big threat for the waste incineration because of the dioxin generation and equipment corrosion. Recently, dechlorination and detoxification of COWs is emergent in order to lower the environmental risk and treatment costs. In this study, base-catalyzed decomposition processes with different hydroxides, hydrogen donors, and catalysts were conducted for pre-treatment of COWs to reduce organic chlorine content, with the TCB as a model compound and industrial rectification residues for verification. Results showed that maximum chlorine retention efficiency (CRE) of four alkalis followed the order of KOH > NaOH-KOH > NaOH > Mg(OH)2, which were 98.3%, 93.4%, 97.2%, and 1.5%, respectively, and could be expressed as an apparent first-order reaction. The differences were resulted from the varying ionic potentials of the metal cations. Hydrogen donors (glycol, glycerol, paraffin oil, and PEG 200) acted as effective dechlorination regents follow the order of PEG > glycol > paraffin oil > glycerol. In addition, Fe, Ni, Cu, and activated carbon catalysts increased the CRE by 68.9% to 92.4%, 91.9%, 89.2%, and 73.3%, respectively. Residue analysis through X-ray diffraction and Fourier transform infrared spectroscopy revealed that KCl, sodium oxalate, and phenol were the main products and a plausible stepwise dechlorination pathway was proposed. The effectiveness of three optimized combinations including NaOH/PEG, KOH/PEG, and NaOH-KOH/PEG (with the Fe catalyst) was confirmed by using them for dechlorinating rectification residues, and they restrained 98.2%, 91.2%, and 94.6% of the chlorine, respectively. The organochlorine content decreased from 19.2 to 1.8% within 180 min, while inorganic chorine content increased from 1.5 to 18.9%, indicating the potential for COWs dechlorination.

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Anti-vicinal diboronates were fabricated from easily available diarylethynes and B2pin2 via a base-catalyzed domino-borylation-protodeboronation (DBP) strategy under transition-metal-free conditions. Under the standard conditions, reactants with a range of different classes of functional groups on the rings, such as MeO, MeS, CF3O, Me2N, TMS, I, Br, Cl, F, and the thiophene ring, were tolerated. Downstream transformation of the vicinal diboronates provided a facile pathway for obtaining vicinal diols by mild oxidation with NaBO3, and a new deuteriation technique was developed in order to acquire 1,2-diarylethanes-1,2-d2 and 1,2-diarylethanes-1,1,2,2-d4. The new deuteriation strategy developed in this study may provide a new research direction for deuteriation chemistry.

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Phytoecdysteroids exert their non-hormonal anabolic and adaptogenic effects in mammals, including humans, through a partially revealed mechanism of action involving the activation of protein kinase B (Akt). We have recently found that poststerone, a side-chain cleaved in vivo metabolite of 20-hydroxyecdysone, exerts potent anabolic activity in rats. Here we report the semi-synthetic preparation of a series of side-chain cleaved ecdysteroids and their activity on the Akt phosphorylation in murine skeletal muscle cells. Twelve C-21 ecdysteroids including 8 new compounds were obtained through the oxidative side-chain cleavage of various phytoecdysteroids, or through the base-catalyzed autoxidation of poststerone. The complete 1H and 13C NMR spectroscopic assignments of the new compounds are presented. Among the tested compounds, 9 could activate Akt stronger than poststerone revealing that side-chain cleaved derivatives of phytoecdysteroids other than 20-hydroxyecdysone are valuable bioactive metabolites. Thus, our results suggest that the expectable in vivo formation of such compounds should contribute to the bioactivity of herbal preparations containing ecdysteroid mixtures.

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BACKGROUND: Lignin is a potential feedstock for microbial conversion into various chemicals. However, the degradation rate of native or technical lignin is low, and depolymerization is needed to obtain reasonable conversion rates. In the current study, base-catalyzed depolymerization-using NaOH (5 wt%)-of softwood Kraft lignin was conducted in a continuous-flow reactor system at temperatures in the range 190-240 °C and residence times of 1 or 2 min. The ability of growth of nine bacterial strains belonging to the genera Pseudomonas and Rhodococcus was tested using the alkaline-treated lignin as a sole carbon source. RESULTS: Pseudomonas fluorescens and Rhodococcus opacus showed the best growth of the tested species on plates with lignin. Further evaluation of P. fluorescens and R. opacus was made in liquid cultivations with depolymerized lignin (DL) at a concentration of 1 g/L. Size exclusion chromatography (SEC) showed that R. opacus consumed most of the available lower molecular weight compounds (approximately 0.1-0.4 kDa) in the DL, but the weight distribution of larger fractions was almost unaffected. Importantly, the consumed compounds included guaiacol-one of the main monomers in the DL. SEC analysis of P. fluorescens culture broth, in contrast, did not show a large conversion of low molecular weight compounds, and guaiacol remained unconsumed. However, a significant shift in molecular weight distribution towards lower average weights was seen. CONCLUSIONS: Rhodococcus opacus and P. fluorescens were identified as two potential microbial candidates for the conversion/consumption of base-catalyzed depolymerized lignin, acting on low and high molecular weight lignin fragments, respectively. These findings will be of relevance for designing bioconversion of softwood Kraft lignin.

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Unpredictable degradation of Ezetimibe solutions in pure acetonitrile occurs when they are stored in glass HPLC vials. The occurrence of the two main degradation peaks and one minor peak was unpredictable at the time of each sample preparation and over time, it appeared that approximately 15% of the sample solutions in glass HPLC vials would eventually show the degradation peaks. Once the degradation peaks occurred in a particular vial, typically within 24h, they would keep growing until reaching a total yield of about 4-5%. Through a comprehensive investigation, it is determined that the solution degradation is caused by a base-catalyzed process, during which ezetimibe undergoes (1) dimerization to form two dimeric impurities, which have not been reported in the literature, and (2) to a less degree, isomerization to produce an isomeric impurity that has been reported before.

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The base-catalyzed resorcinol-formaldehyde condensation reactions were theoretically investigated in this study by employing a quantum chemistry method. The condensation reaction includes two steps: (1) formation of the quinonemethide (QM) intermediate from hydroxymethylresorcinol; (2) Michael addition between the quinonemethide and resorcinol anion. The first step is the rate-determining step. Two mechanisms, unimolecular elimination of the conjugate base (E1cb) and water-aided elimination (WAE), were identified for the formation of QM. The hydroxymethylresorcinol anion produces neutral QM while the dianion produces a quinonemethide anion (QMA). The calculated potential energy barriers suggested that the QMA formation is much more favorable. Although resorcinol-formaldehyde and phenol-formaldehyde condensations share a common mechanism, the former would be faster if the QMA participates in condensations. The potential energy barriers for formation of 2-QM, 4-QM, 6-QM, 2-QMA, and 4-QMA were calculated. The results show that the formations of 6-QM and 4-QMA have relatively lower energy barriers. This rationalized previous experimental observations that the 2,4-(2,6-) and 6,6'-(4,4'-) methylene linkages were dominant, whereas the 2,2'-linkage was almost absent. The resorcinol-phenol-formaldehyde co-condensations were also calculated. The cold-setting characteristic of phenol-resorcinol-formaldehyde co-condensed resin can be attributed to participation of resorcinol quinonemethides in condensations.

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Base-catalyzed urea⁻formaldehyde condensation reactions were investigated by using a quantum chemistry method. It was found that monomethylolurea or N,N'-dimethylolurea can produce the methyleneurea intermediate (⁻HN⁻CO⁻N=CH2) with the catalysis of base. The E1cb (unimolecular elimination of conjugate base) mechanism was identified for the formation of such an intermediate. The potential energy barrier was theoretically predicted to be 59.6 kJ/mol for the E1cb step, which is about half of that of previously proposed SN2 (bimolecular nucleophilic substitution) mechanism. In the subsequentcondensation reactions, Michael addition reactions that lead to different condensed structures can occur between the methyleneurea intermediate and the anions produced from methylolureas under alkaline conditions. Based on the theoretical calculations on the kinetics and thermodynamics of the selected reactions, the competitive formations of methylene linkages, ether linkages and uron were discussed in combination with our previous experimental observations.

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Concentration effects in the base-catalyzed hydrolysis of water-soluble methacrylates (3-(N,N-dimethylaminoethyl) methacrylate (DMAEMA), 2-hydroxyethyl methacrylate (HEMA) and oligo(ethylene glycol) methacrylates (OEGMAs)) have been studied. These monomers are rapidly hydrolyzed in the presence of bases at the room temperature in dilute aqueous solutions, but the reaction rate decreases sharply in highly concentrated solutions. A clear correlation was found between a form of the viscosity isotherm for DMAEMA solutions and the concentration dependence of the autocatalytic hydrolysis rate which indicates the connection of process kinetics with the structure of solutions. These data should be considered when carrying out homo- and copolymerization of the previously mentioned monomers in aqueous solutions.

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Graphene oxide (GO) and reduced graphene oxide (RGO) materials contain a variety of surface O-functional groups that are chemically reactive. When released into the environment these materials may significantly affect the abiotic transformation of organic contaminants, and therefore, may alter their fate and risks. We found that two GO and five RGO materials that varied in C/O ratio, hydrophobicity, and type/distribution of surface O-functionality all had catalytic effects on the dehydrochlorination of 1,1,2,2-tetrachloroethane (TeCA). Even though the catalytic effects of the materials originated from their deprotonated surface O-functional groups, which served as conjugated bases to catalyze the reaction, the catalytic efficiencies of the materials did not correlate strongly with their surface O contents. The spectroscopic evidence (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy), surface charge data, and adsorption experiments demonstrated that the catalytic efficiencies of the GO/RGO materials were controlled by a complex interplay of the type and distribution of surface O-functionality, as well as adsorption affinity of the materials. Both Ca(2+) and Mg(2+) inhibited the catalytic efficiency of the materials by binding to the surface O-functional groups, and consequently, decreasing the basicity of the functional groups. At an environmentally relevant concentration of 10 mg/L, Suwannee River humic acid (used as a model dissolved organic matter) alone had little effect on the dehydrochlorination of TeCA. However, it could inhibit the catalytic efficiency of the GO/RGO materials by coating on their surface and thus, decreasing the adsorption affinity of these materials for TeCA. The findings further underline the potentially important impacts of nanomaterials on contaminant fate and effects in the environment.

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