Benzimidazole derivatives have been shown to possess sirtuin-inhibitory activity. In the continuous search for potent sirtuin inhibitors, systematic changes on the terminal benzene ring were performed on previously identified benzimidazole-based sirtuin inhibitors, to further investigate their structure-activity relationships. It was demonstrated that the sirtuin activities of these novel compounds followed the trend where meta-substituted compounds possessed markedly weaker potency than ortho- and para-substituted compounds, with the exception of halogenated substituents. Molecular docking studies were carried out to rationalize these observations. Apart from this, the methods used to synthesize the interesting compounds are also discussed.
2-(4-Chlorophenyl)-2-oxoethyl 3-nitrobenzoate is synthesized by reacting 4-chlorophenacyl bromide with 3-nitrobenzoic acid using a slight excess of potassium or sodium carbonate in DMF medium at room temperature. The structure of the compound was confirmed by IR and single-crystal X-ray diffraction studies. FT-IR spectrum of 2-(4-chlorophenyl)-2-oxoethyl 3-nitrobenzoate was recorded and analyzed. The crystal structure is also described. The vibrational wavenumbers were computed using HF and DFT methods and are assigned with the help of potential energy distribution method. The first hyperpolarizability and infrared intensities are also reported. The geometrical parameters of the title compound obtained from XRD studies are in agreement with the calculated (DFT) values. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The HOMO and LUMO analysis are used to determine the charge transfer within the molecule. MEP was performed by the DFT method.
Enzymatic halogenation captures scientific interest considering its feasibility in modifying compounds for chemical diversity. Currently, majority of flavin-dependent halogenases (F-Hals) were reported from bacterial origin, and as far as we know, none from lichenized fungi. Fungi are well-known producers of halogenated compounds, so using available transcriptomic dataset of Dirinaria sp., we mined for putative gene encoding for F-Hal. Phylogenetic-based classification of the F-Hal family suggested a non-tryptophan F-Hals, similar to other fungal F-Hals, which mainly act on aromatic compounds. However, after the putative halogenase gene from Dirinaria sp., dnhal was codon-optimized, cloned, and expressed in Pichia pastoris, the ~63 kDa purified enzyme showed biocatalytic activity towards tryptophan and an aromatic compound methyl haematommate, which gave the tell-tale isotopic pattern of a chlorinated product at m/z 239.0565 and 241.0552; and m/z 243.0074 and 245.0025, respectively. This study is the start of understanding the complexities of lichenized fungal F-hals and its ability to halogenate tryptophan and other aromatic. compounds which can be used as green alternatives for biocatalysis of halogenated compounds.
The effectiveness of combined nanofiltration and disinfection processes was studied by comparing the pre-disinfection and post-disinfection when in combination with nanofiltration. Four types of sulfonamide (sulfanilamide, sulfadiazine, sulfamethoxazole, and sulfadimethoxine) were chosen as substrates, with sodium hypochlorite as a disinfectant. A laboratory-scale nanofiltration system was used to conduct the following sets of experiment: (1) a pre-chlorination system, where the free active chlorine (FAC) was added to the membrane influent; and (2), a post-chlorination system, where the FAC was added to the membrane effluent. Overall, the pre-disinfection nanofiltration system showed higher sulfonamide removal efficiency compared to the post-chlorination nanofiltration system (>99.5% versus >89.5%). In the case of limited FAC ([FAC]0: [sulfonamide]0≤1), the removal efficiency for the post-chlorination nanofiltration system was higher, due to the prior nanofiltration process that could remove 12.5% to 80% of sulfonamide. The flux of the treated feed system was considerably higher than in the untreated feed system; however, the membrane was observed to be slightly damaged due to residual chlorine attack.
Mefenamic acid (Mfe) is one of the most frequently detected nonsteroidal anti-inflammatory drugs in the environment. This study investigated the kinetics and the transformation by-products of Mfe during aqueous chlorination. The potential ecotoxicity of the transformation by-products was also evaluated. In the kinetic study, the second-order rate constant (kapp) for the reaction between Mfe and free available chlorine (FAC) was determined at 25 ± 0.1 °C. The result indicated that the degradation of Mfe by FAC is highly pH-dependent. When the pH was increased from 6 to 8, it was found that the kapp for the reaction between Mfe and FAC was decreased from 16.44 to 4.4 M(-1) s(-1). Characterization of the transformation by-products formed during the chlorination of Mfe was carried out using liquid chromatography-quadrupole time-of-flight accurate mass spectrometry. Four major transformation by-products were identified. These transformation by-products were mainly formed through hydroxylation, chlorination and oxidation reactions. Ecotoxicity assessment revealed that transformation by-products, particularly monohydroxylated Mfe which is more toxic than Mfe, can be formed during aqueous chlorination.
Halogenated compounds are recalcitrant environmental pollutants prevalent in agricultural fields, waste waters and industrial by-products, but they can be degraded by dehalogenase-containing microbes. Notably, 2-haloalkanoic acid dehalogenases are employed to resolve optically active chloropropionates, as exemplified by the d-specific dehalogenase from Rhizobium sp. RCI (DehD), which acts on d-2-chloropropionate but not on its l-enantiomer. The catalytic residues of this dehalogenase responsible for its affinity toward d-2-chloropropionate have not been experimentally determined, although its three-dimensional crystal structure has been solved. For this study, we performed in silico docking and molecular dynamic simulations of complexes formed by this dehalogenase and d- or l-2-chloropropionate. Arg134 of the enzyme plays the key role in the stereospecific binding and Arg16 is in a position that would allow it to activate a water molecule for hydrolytic attack on the d-2-chloropropionate chiral carbon for release of the halide ion to yield l-2-hydroxypropionate. We propose that within the DehD active site, the NH group of Arg134 can form a hydrogen bond with the carboxylate of d-2-chloropropionate with a strength of ∼4 kcal/mol that may act as an acid-base catalyst, whereas, when l-2-chloropropionate is present, this bond cannot be formed. The significance of the present work is vital for rational design of this dehalogenase in order to confirm the involvement of Arg16 and Arg134 residues implicated in hydrolysis and binding of d-2-chloropropionate in the active site of d-specific dehalogenase from Rhizobium sp. RC1.
Co-pyrolysis of brominated flame retardants (BFRs) with polymeric materials prevails in scenarios pertinent to thermal recycling of bromine-laden objects; most notably the non-metallic fraction in e-waste. Hydro-dehalogenation of aromatic compounds in a hydrogen-donating medium constitutes a key step in refining pyrolysis oil of BFRs. Chemical reactions underpinning this process are poorly understood. Herein, we utilize accurate density functional theory (DFT) calculations to report thermo-kinetic parameters for the reaction of solid polyethylene, PE, (as a surrogate model for aliphatic polymers) with prime products sourced from thermal decomposition of BFRs, namely, HBr, bromophenols; benzene, and phenyl radical. Facile abstraction of an ethylenic H by Br atoms is expected to contribute to the formation of abundant HBr concentrations in practical systems. Likewise, a relatively low energy barrier for aromatic Br atom abstraction from a 2-bromophenol molecule by an alkyl radical site, concurs with the reported noticeable hydro-debromination capacity of PE. Pathways entailing a PE-induced bromination of a phenoxy radical should be hindered in view of high energy barrier for a Br transfer into the para position of the phenoxy radical. Adsorption of a phenoxy radical onto a Cu(Br) site substituted at the PE chain affords the commonly discussed PBDD/Fs precursor of a surface-bounded bromophenolate adduct. Such scenario arises due to the heterogeneous integration of metals into the bromine-rich carbon matrix in primitive recycling of e-waste and their open burning.
The high dependency and surplus use of agrochemical products have liberated enormous quantities of toxic halogenated pollutants into the environment and threaten the well-being of humankind. Herein, this study performed molecular docking, molecular dynamic (MD) simulations, molecular mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculations on the DehH2 from Bacillus thuringiensis, to identify the order of which the enzyme degrades different substrates, haloacids, haloacetate and chlorpyrifos. The study discovered that the DehH2 favored the degradation of haloacids and haloacetates (-3.3 - 4.6 kcal/mol) and formed three hydrogen bonds with Asp125, Arg201 and Lys202. Despite the inconclusive molecular docking result, chlorpyrifos was consistently shown to be the least favored substrate of the DehH2 in MD simulations and MM-PBSA calculations. Results of MD simulations revealed the DehH2-haloacid- (RMSD 0.15 - 0.25 nm) and DehH2-haloacetates (RMSF 0.05 - 0.25 nm) were more stable, with the DehH2-L-2CP complex being the most stable while the least was the DehH2-chlorpyrifos (RMSD 0.295 nm; RMSF 0.05 - 0.59 nm). The Molecular Mechanics Poisson-Boltzmann Surface Area calculations showed the DehH2-L-2CP complex (-24.27 kcal/mol) having the lowest binding energy followed by DehH2-MCA (-22.78 kcal/mol), DehH2-D-2CP (-21.82 kcal/mol), DehH2-3CP (-21.11 kcal/mol), DehH2-2,2-DCP (-18.34 kcal/mol), DehH2-2,3-DCP (-8.34 kcal/mol), DehH2-TCA (-7.62 kcal/mol), while chlorpyrifos was unable to spontaneously bind to DehH2 (+127.16 kcal/mol). In a nutshell, the findings of this study offer valuable insights into the rational tailoring of the DehH2 for expanding its substrate specificity and catalytic activity in the near future.Communicated by Ramaswamy H. Sarma.
Dicofol, an extensively used organochlorine pesticide and a recommended Stockholm convention persistent organic pollutant (POP) candidate is well known for its endocrine disruptive properties. The sonochemical degradation of Dicofol in aqueous media has been investigated using a 20-kHz probe type sonicator with power inputs from 150 to 450 W. The degradation rate was determined as a function of concentration of Dicofol, solution pH, bulk phase temperature, ultrasonic power density and H2O2 addition. At optimum operating conditions, the pseudo-first-order degradation rate constant (k) was determined to be 0.032 min-1 and the extent of degradation was found to be 86% within 60 min of ultrasound treatment. High performance liquid chromatography (HPLC) and Gas chromatography coupled with mass spectroscopy (GC-MS) analysis indicated the presence of degraded products. The obtained results of Dicofol degradation and control experiments in the presence of H2O2 and radical scavenger test suggest thermal decomposition along with radical attack at bubble-vapor interface to be the dominant degradation pathway. Sonochemical treatment is effective and promising for successful removal of harmful pesticides such as Dicofol and superior removal efficiency for other POPs is expected in the near future with the successful implementation of ultrasound-based wastewater treatment.
Safe immunostimulants (adjuvants) are essential for the development of highly potent peptide-based vaccines. This study examined for the first time whether fluorinated lipids could stimulate humoral immunity in vivo when conjugated to peptide antigen. The impact of fluorination on humoral immunity was tested using a library of peptide-based vaccine candidates against the group A streptococcus (GAS). The fluorinated constructs stimulated similar mouse IgG titers to those elicited by complete Freund's adjuvant (CFA) and were higher than those produced in mice that received the nonfluorinated constructs.
Chlorination is a common disinfection method in water treatment. This method can be converted into an advanced oxidation process by incorporating UV irradiation during water treatment. This study investigated the degradation of hydrochlorothiazide (HCTZ) by chlorination and UV/chlorination in water. HCTZ is a diuretic medication that has been frequently detected in wastewater. For chlorination, the second-order rate constant for the reaction between HCTZ with free available chlorine was found to increase with increasing pH from 5 to 8 due to the increase of the anionic HCTZ fraction. UV/chlorination was found to be more efficient in removing HCTZ as compared with chlorination due to the presence of reactive radical species such as hydroxyl radicals. For transformation by-products, chlorination was found to produce two by-products via chlorination and hydroxylation reactions that occurred at the aromatic ring of HCTZ. For UV/chlorination, an additional by-product formed through a radical reaction at the heterocyclic moiety of HCTZ was detected. Based on the Escherichia coli inhibition study, chlorination and UV/chlorination were found to increase the toxicity of the HCTZ solution. This result indicated that even UV/chlorination showed higher effectiveness in removing HCTZ; however, it also has the potential to generate toxic by-products and effluent.
Chlorinated compounds such as sphingolipid-based organochlorine compounds are precursors for the formation of 3-monochlororopanediol (3-MCPD) esters in palm oil. This study evaluates the effects of several factors within the palm oil supply chain on the levels of sphingolipid-based organochlorine, which in turn may influence the formation of 3-MCPD esters during refining. These factors include application of inorganic chlorinated fertiliser in the oil palm plantation, bruising and degradation of oil palm fruits after harvest, recycling of steriliser condensate as water for dilution of crude oil during oil palm milling, water washing of palm oil and different refining conditions. It was observed that bruised and degraded oil palm fruits showed higher content of sphingolipid-based organochlorine than control. In addition, recycling steriliser condensate during milling resulted in elevated content of sphingolipid-based organochlorine in palm oil. However, the content of sphingolipid-based organochlorine compounds was reduced by neutralisation, degumming and bleaching steps during refining. Although water washing of crude palm oils (CPO) prior to refining did not reduce the content of sphingolipid-based organochlorine, it did reduce the formation of 3-MCPD esters through the removal of water-soluble chlorinated compounds. It was found that the use of inorganic chlorinated fertiliser in plantations did not increase the content of chlorinated compounds in oil palm fruits and extracted oil, and hence chlorinated fertiliser does not seem to play a role in the formation of 3-MCPD esters in palm oil. Overall, this study concluded that lack of freshness and damage to the fruits during transport to mills, combined with water and oil recycling in mills are the major contributors of chlorinated precursor for 3-MCPD esters formation in palm oil.
Halogenated polycyclic aromatic hydrocarbons (HPAHs, H = F, Cl, Br) are a new class of PAHs derivatives that mainly originate from the incomplete combustion of halogen-laden materials and via metallurgical operations. These compounds circulate extensively in various environmental matrices. This survey provides a comprehensive review on governing synthesis routes of HPAHs, their environmental occurrence, and their health and ecological effects. The review comprehensively enlists and presents emission sources of these emerging organic pollutants into the air that serves as their main reservoir. The formation of HPAHs ensues through successive addition reactions of related precursors accompanied by ring cyclization steps; in addition to direct unimolecular fragmentation of parents halogenated. Halogenation of parent PAHs rapidly occurs in saline ecosystems, thus multiplying the availability of these notorious compounds in the environment. Certain HPAHs appear to be more carcinogenic than dioxins. Transmission routes of HPAHs from their emission sources to water bodies, soil, aquatic life, plants, terrestrial animals, and humans are well-documented. Later, the direct and indirect diffusion of HPAHs from air to the biotic (plants, animals, humans) and abiotic components (soil, water, sediments) are described in detail. The study concludes that HPAHs are permeable to the carbon matrices resulting in the alleviation of the source-to-sink interface. As a potential future perspective, understanding the transmission interfaces lays a foundation to intervene in the introduction of these toxicants into the food chain.
Polybrominated diphenyl ethers (PBDEs) are extensively used as flame retardants in many consumer products, and leachates from landfills have been identified as one of the possible sources of PBDEs in the environment. Meanwhile, the unprecedented economic and population growths of some Asian countries over the last decade have led to significant increases in the amount of waste containing PBDEs in that region. This study investigates the status of PBDEs in leachates from municipal solid waste dumping sites (MSWDS) in tropical Asian countries. A total of 46 PBDE congeners were measured, both in the adsorbed (n=24) and dissolved (n=16) phases, in leachate samples collected, from 2002 to 2010, from ten MSWDS distributed among the eight countries of Lao PDR, Cambodia, Vietnam, India, Indonesia, Thailand, the Philippines, and Malaysia. PBDEs were predominantly found in the adsorbed phase. Partitioning of PBDEs in the dissolved phase was associated with the presence of dissolved organic matter; the apparent organic carbon-normalized partition coefficients (K'oc) of the BDE congeners were lower by two to four orders of magnitude than the K oc predicted from the octanol-water partition coefficients (K ow). The total PBDE concentrations from mono- to deca-BDEs ranged from 3.7 to 133,000 ng/L, and showed a trend toward higher concentrations in the more populous and industrialized Asian countries. The congener profiles in the leachates basically reflected the composition of PBDE technical mixtures. The occurrence of congeners not contained, or in trace concentrations, in technical products (e.g., BDEs 208, 207, 206, 202, 188, 179, 49, 17/25, 8, 1) was observed in most of the leachate samples, suggesting the debromination of technical mixtures, including BDE-209, in the MSWDS of tropical Asian countries. Moreover, the temporal trend indicated the reduction of BDE-209 over time, with a corresponding increase in and/or emergence of lower brominated PBDE congeners. The results indicated that MSWDS of tropical Asian countries are potential sources of environmental PBDEs, which may be transported to the aquatic environment via dissolution with dissolved organic matter. MSWDS could be amplifiers of PBDE toxicity in the environment, possibly through debromination.
This paper describes an efficient and regioselective method for the synthesis of novel fluorinated spiro-heterocycles in excellent yield by cascade [5+1] double Michael addition reactions. The compounds 7,11-bis(4-fluorophenyl)-2,4-dimethyl- 2,4-diazaspiro[5.5] undecane-1,3,5,9-tetraone (3a) and 2,4-dimethyl-7,11-bis (4-(trifluoromethyl)phenyl)-2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraone (3b) were characterized by single-crystal X-ray diffraction, FT-IR and NMR techniques. The optimized geometrical parameters, infrared vibrational frequencies and NMR chemical shifts of the studied compounds have also been calculated using the density functional theory (DFT) method, using Becke-3-Lee-Yang-Parr functional and the 6-311G(d,p) basis set. There is good agreement between the experimentally determined structural parameters, vibrational frequencies and NMR chemical shifts of the studied compounds and those predicted theoretically. The calculated natural atomic charges using NBO method showed higher polarity of 3a compared to 3b.The calculated electronic spectra are also discussed based on the TD-DFT calculations.
The non-stereospecific α-haloalkanoic acid dehalogenase DehE from Rhizobium sp. RC1 catalyzes the removal of the halide from α-haloalkanoic acid D,L-stereoisomers and, by doing so, converts them into hydroxyalkanoic acid L,D-stereoisomers, respectively. DehE has been extensively studied to determine its potential to act as a bioremediation agent, but its structure/function relationship has not been characterized. For this study, we explored the functional relevance of several putative active-site amino acids by site-specific mutagenesis. Ten active-site residues were mutated individually, and the dehalogenase activity of each of the 10 resulting mutants in soluble cell lysates against D- and L-2-chloropropionic acid was assessed. Interestingly, the mutants W34→A,F37→A, and S188→A had diminished activity, suggesting that these residues are functionally relevant. Notably, the D189→N mutant had no activity, which strongly implies that it is a catalytically important residue. Given our data, we propose a dehalogenation mechanism for DehE, which is the same as that suggested for other non-stereospecific α-haloalkanoic acid dehalogenases. To the best of our knowledge, this is the first report detailing a functional aspect for DehE, and our results could help pave the way for the bioengineering of haloalkanoic acid dehalogenases with improved catalytic properties.
Two new non-halogenated sesquiterpenes, snakeol (1) and snakediol (2) were isolated together with 9 known sesquiterpenes such as (R,Z)-33-dimethyl-5-methylene-4-(3-methylpenta-24-dien-1-yl)cyclohex-1-ene (3), palisol (4), pacifigorgiol (5), palisadin D (6), palisadin A (7), palisadin B (8), 5-acetoxypalisadin B (9), debromolaurinterol (10) and α-bromocuparane (11) from the red algae Laurencia snackeyi. The structures of two new metabolites were determined from their spectroscopic data (IR, 1D and 2D NMR and MS). Compounds 1, 2, 10 and 11 showed strong antibacterial activity against selected human clinical bacterial pathogens.
This study investigated chlorinated transformation products (TPs) and their parent micropollutants, aromatic pharmaceuticals and personal care products (PPCPs) in the urban water bodies of two metropolitan cities. Nine PPCPs and 16 TPs were quantitatively or semi-quantitatively determined using isotope dilution techniques and liquid chromatography-tandem mass spectrometry. TPs and most PPCPs were effectively removed by conventional wastewater treatments in a wastewater treatment plant (WWTP). Chlorinated parabens and all PPCPs (at concentrations below 1000 ng/L) were present in the waters receiving treated wastewater. By contrast, the waters receiving untreated wastewater contained higher levels of PPCPs (up to 9400 ng/L) and more species of chlorinated TPs including chlorinated parabens, triclosan, diclofenac, and bisphenol A. The very different chemical profiles between the water bodies of the two cities of similar geographical and climatic properties may be attributed to their respective uses of chemicals and policies of wastewater management. No apparent increase in the number of species or abundances of TPs was observed in either the chlorinated wastewater or the seawater rich in halogens. This is the first study to elucidate and compare the profiles of multiple TPs and their parent PPCPs in the water bodies of coastal cities from tropical islands. Our findings suggest that chlorinated derivatives of bisphenol A, diclofenac, triclosan, and parabens in the surface water originate from sources other than wastewater disinfection or marine chlorination. Although further studies are needed to identify the origins, conventional wastewater treatments may protect natural water bodies against contamination by those chlorinated substances.
During our studies on Malaysian Laurencia species, brominated metabolites, tiomanene, acetylmajapolene B, and acetylmajapolene A were isolated from an unrecorded species collected at Pulau Tioman, Pahang along with known majapolene B and majapolene A. Acetylmajapolene A was a mixture of diastereomers as in the case of majapolene A. Tiomanene may be a plausible precursor for acetylmajapolenes B and A. In addition, three known halogenated sesquiterpenes and two known halogenated C(15) acetogenins were found from other two unrecorded species collected at Pulau Karah, Terengganu and Pulau Nyireh, Terengganu, respectively. Some of these halogenated metabolites showed moderate antibacterial activity against some marine bacteria.