Ag(I) Pyridine-Amidoxime Complex as the Catalysis Activity Domain for the Rapid Hydrolysis of Organothiophosphate-Based Nerve Agents: Mechanistic Evaluation and Application.

Two novel Ag(I) complexes containing synergistic pyridine and amidoxime ligands (Ag-DPAAO and Ag-PAAO) were first designed as complex monomers. Taking advantage of the molecular imprinting technique and solvothermal method, molecular imprinted porous cross-linked polymers (MIPCPs) were developed as a robust platform for the first time to incorporate Ag-PAAO into a polymer material as a recyclable catalyst. Advantageously, the observed pseudo first-order rate constant (kobs) of MIPCP-Ag-PAAO-20% for ethyl-parathion (EP) hydrolysis is about 1.2 × 104-fold higher than that of self-hydrolysis (30 °C, pH = 9). Furthermore, the reaction mechanism of the MIPCP-containing Ag-PAAO-catalyzed organothiophosphate was analyzed in detail using density functional theory and experimental spectra, indicating that the amidoxime can display dual roles for both the key coordination with the silver ion and nucleophilic attack to weaken the P-OAr bond in the catalytic active site.

Efficient and selective extraction of azamethiphos and chlorpyrifos residues from mineral water and grape samples using magnetic mesoporous molecularly imprinted polymer.

A magnetic mesoporous molecularly imprinted polymers was synthesized on the surface of magnetic nanoparticles silanized with 3-(trimethoxysilyl) propyl methacrylate to introduce reactive methacrylate groups. Subsequently, methacrylic acid monomers were grafted onto the surface of this adsorbent functionalized via polymerization by precipitation. Magnetic mesoporous molecularly imprinted polymer was properly characterized by different techniques and applied as adsorbent in magnetic solid phase extraction for selective determination of two organophosphorus pesticides, azamethiphos and chlorpyrifos, in mineral water and grape samples. After sample preparation optimization, recoveries of 99.56% and 98.86% were obtained for azamethiphos and chlorpyrifos, respectively. The magnetic solid phase extraction coupled to HPLC-UV presented limit of quantification of 5 ng mL-1, linearity ranged of 5 to 1000 ng mL-1, in addition to adequate accuracy, precision and robustness. The pesticides showed stability in the matrix and were satisfactorily quantified in real mineral water and grape samples.

Enantioselective Uptake Determines Degradation Selectivity of Chiral Profenofos in Cupriavidus nantongensis X1T.

Organophosphorus insecticides account for approximately 28% of the global commercial insecticide market, while 40% of them are chiral enantiomers. Chiral enantiomers differ largely in their toxicities. Enantiomers that are less active or inactive do not offer the needed efficacy but pollute the environment and cause toxicities to non-target species. Cupriavidus nantongensis X1T, a recently isolated bacterial strain, could degrade S-profenofos 2.3-fold faster than R-profenofos, while the latter is the active enantiomer potently against pest insects and has greater mammalian safety. The degradation enzyme encoded by opdB was expressed via Escherichia coli and purified. The degradation kinetics of R- and S-profenofos showed that both the purified OpdB and crude enzyme extracts had no enantiomer degradation selectivity, which strongly indicated that the degradation selectivity occurred in the uptake process. Metabolite analyses suggested a novel dealkylation pathway. This is the first report of bacterial selective uptake of organophosphates. Selective degradation of S-profenofos over R-profenofos by the strain X1T suggests a concept of co-application of racemic pesticides and degradation-selective bacteria to minimize contamination and non-target toxicity problems.

Characterization of Dialkyldithiophosphates as Slow Hydrogen Sulfide Releasing Chemicals and Their Effect on the Growth of Maize.

Hydrogen sulfide is a key gasotransmitter for plants and has been shown to greatly increase their growth and survival in the presence of environmental stressors. Current methods for slowly releasing hydrogen sulfide use chemicals, such as GYY-4137, but these result in the release of chemicals not found in the environment, and chemicals used may lack structures that can be readily tuned to affect the rate of release of hydrogen sulfide. In this article, we describe the synthesis and slow release of hydrogen sulfide from dialkyldithiophosphates, which are a new set of hydrogen sulfide releasing chemicals that can be used in agriculture. The rates of hydrolysis of dibutyldithiophosphate and GYY-4137 were measured in water at 85 °C and compared with each other to investigate their differences. GYY-4137 is widely used as a chemical that slowly releases H2S, but its rate of release was not previously quantified. The release of hydrogen sulfide in water at room temperature was measured for a series of dialkyldithiophosphates using a hydrogen sulfide electrode. It was shown that the structure of the dialkyldithiophosphate affected the amount of hydrogen sulfide released. The final degradation products of dibutyldithiophosphate were shown to be phosphoric acid and butanol, which are chemicals found in the environment. This result was notable because it demonstrated that dialkyldithiophosphates degrade to safe, natural chemicals that will not pollute the environment. To demonstrate that dialkyldithiophosphates have potential applications in agriculture, maize was grown for 4.5 weeks after exposure to 1-200 mg of dibutyldithiophosphate, and the weight of corn plants increased by up to 39% at low loadings of dibutyldithiophosphate.

Experimental design of switchable solvent-based liquid phase microextraction for the accurate determination of etrimfos from water and food samples at trace levels by GC-MS.

Presented in this study is a simple but efficient switchable polarity solvent microextraction strategy for etrimfos preconcentration from water and food samples for quantification by gas chromatography mass spectrometry. Repeatability of the extraction process and instrumental measurements were enhanced by using deuterated bisphenol A as internal standard. Significant parameters of the extraction method were fitted into an experimental design model to study the effects of parameters on extraction output, as well as mutual effects of combined parameters. The design model was formed with 51 experimented data obtained from the combination of sodium hydroxide volume, switchable solvent volume, and vortex period at three levels. The method was validated by applying optimum conditions attained from the model predictor. The detection limit was found to be 1.3 ng/mL and it corresponded to an enhancement factor of about 54 folds when compared to direct GC-MS measurement. Etrimfos was not detected in the water and food samples tested but the results (92-107%) obtained from spiked recovery experiments established that etrimfos when present in the selected matrices can be accurately and precisely quantified.

Assessment of the endocrine-disrupting effects of organophosphorus pesticide triazophos and its metabolites on endocrine hormones biosynthesis, transport and receptor binding in silico.

Triazophos (TAP) was a widely used organophosphorus insecticide in developing countries. TAP could produce specific metabolites triazophos-oxon (TAPO) and 1-phenyl-3-hydroxy-1,2,4-triazole (PHT) and non-specific metabolites diethylthiophosphate (DETP) and diethylphosphate (DEP). The objective of this study involved computational approaches to discover potential mechanisms of molecular interaction of TAP and its major metabolites with endocrine hormone-related proteins using molecular docking in silico. We found that TAP, TAPO and DEP showed high binding affinity with more proteins and enzymes than PHT and DETP. TAP might interfere with the endocrine function of the adrenal gland, and TAP might also bind strongly with glucocorticoid receptors and thyroid hormone receptors. TAPO might disrupt the normal binding of androgen receptor, estrogen receptor, progesterone receptor and adrenergic receptor to their natural hormone ligands. DEP might affect biosynthesis of steroid hormones and thyroid hormones. Meanwhile, DEP might disrupt the binding and transport of thyroid hormones in the blood and the normal binding of thyroid hormones to their receptors. These results suggested that TAP and DEP might have endocrine disrupting activities and were potential endocrine disrupting chemicals. Our results provided further reference for the comprehensive evaluation of toxicity of organophosphorus chemicals and their metabolites.

Catalytic Chemosensing Assay for Selective Detection of Methyl Parathion Organophosphate Pesticide.

Herein, a catalytic chemosensing assay (CCA), based on a bimetallic complex, [RuII (bpy)2 (CN)2 ]2 (CuI I)2 (bpy=2,2'-bipyridine), is described. This complex integrates a task-specific catalyst (CuI -catalyst) and a signaling unit ([RuII (bpy)2 (CN)2 ]) to specifically hydrolyze methyl parathion, a highly toxic organophosphate (OP) pesticide. The bimetallic complex catalyzed the hydrolysis of the phosphate ester to generate o,o-dimethyl thiophosphate (DTP) anion and 4-nitrophenolate. Intrinsically, 4-nitrophenolate absorbed UV/Vis light at λmax =400 nm, creating the first level of the chemosensing signal. DTP interacted with the original complex to displace the chromophore, [RuII (bpy)2 (CN)2 ], which was monitored by spectrofluorometry; this was classified as the second level of chemosensing signal. By integrating both spectroscopic and spectrofluorometric signals with a simple AND logic gate, only methyl parathion was able to provide a positive response. Other aromatic and aliphatic OP pesticides (diazinon, fenthion, meviphos, terbufos, and phosalone) and 4-nitrophenyl acetate provided negative responses. Furthermore, owing to the metal-catalyzed hydrolysis of methyl parathion, the CCA system led to the detoxification of the pesticide. The CCA system also demonstrated its catalytic chemosensing properties in the detection of methyl parathion in real samples, including tap water, river water, and underground water.

Enhanced Dispersion and Polarization Interactions Achieved through Dithiophosphate Group Incorporation Yield a Dramatic Binding Affinity Increase for an RNA Aptamer-Thrombin Complex.

Regiospecific replacement of a single phosphate (PO2) by a dithiophosphate (PS2) group in an RNA can dramatically increase its binding affinity for a target protein. Thus, complexes between antithrombin and anti-VEGF RNA aptamers with single dithiophosphate moieties and thrombin and VEGF, respectively, display equilibrium dissociation constants KD of ca. 1 pM, 1000-fold tighter than the native RNA complexes (ca. 1 nM). Inspection of crystal structures of the native and PS2-RNA aptamer:thrombin complexes reveals an RNA-induced fit in the latter. This leads to a close approach between PS2 and the phenyl ring edge of Phe-232 that is surrounded by pairs of lysines and arginines. To better understand the origins of the tighter binding and individual contributions to the interaction energy, we carried out QM calculations with phosphate- and dithiophosphate-benzene and dimethyl phosphate- and dimethyl dithiophosphate-benzene model systems. These calculations demonstrate that the dithiophosphate-benzene interaction is much stronger than the corresponding interaction with phosphate. QM/MM calculations with the full complexes confirmed this finding and support the hypothesis that the electric field generated by basic residues surrounding Phe-232 is key to the polarization of the PS2 moiety. Thus, disparate polarization and dispersion energies between the PO2 and PS2 complexes contribute critically to the difference in binding affinity. By comparison, easier desolvation of the dithiophosphate group compared to phosphate does not contribute decisively to the observed difference in binding affinity. Favorable polarization and dispersion energies may be a general feature of the dramatic affinity gains seen for complexes between RNAs carrying dithiophosphate groups and their binding proteins.

Determination of Se(IV) concentration via cathodic stripping voltammetry in the presence of Cu(II) ions and ammonium diethyl dithiophosphate.

The development of a methodology for the determination of Se(IV) concentration via cathodic stripping voltammetry is described in this work. The methodology is based on the formation of copper selenide (Cu2Se), whose reduction signal at -0.60 V has been used as an analytical response to quantify the Se(IV) concentration in solution. The novelty of our methodology is the study of this system in the presence of a ligand such as ammonium diethyl dithiophosphate (ADTTP), which forms complexes with Cu(II) and Se(IV). The results showed that the presence of ADTTP plays an important role, increasing the sensitivity of the determination by almost a factor of two compared with the methodology in the absence of the ligand. The optimized conditions were pH 1.6 (phosphoric acid, 2.0 × 10-2 mol L-1), CCu(II) = 1.5 mg L-1, CADTTP = 2.0 µmol L-1, Eacc = -0.40 V and tacc = 45 s. The detection and the quantification limits obtained were 0.065 and 0.21 µg L-1, respectively, and linearity was maintained up to 4.0 µg L-1 of Se(IV). The sensitivity was 10.26 nA L µg-1. On the other hand, the relative standard deviation for 15 replicate measurements at 1.0 µg L-1 of Se(IV) was 1.6%. The usefulness of the method was evaluated by determining Se(IV) in two certified reference materials (TMDW and TM-28.4) with relative errors of less than 2.0%. The proposed method was successfully applied to the determination of Se(IV) in spiked tap water and in a liquid pharmaceutical formulation with satisfactory results. The developed methodology presents a low detection limit, good repeatability, selectivity and linear range. Furthermore, the sensibility of the method was achieved by applying a short accumulation time (45 s).

Fabrication of silver-coated gold nanoparticles to simultaneously detect multi-class insecticide residues in peach with SERS technique.

Fast sampling and multicomponent detections are important in the analysis of pesticide residues detection. In this work, surface-enhanced Raman scattering (SERS) method based on silver-coated gold nanoparticles (Au@Ag NPs) was used to simultaneously detect multi-class pesticide residues such as thiacloprid (carbamate), profenofos (organophosphate) and oxamyl (neonicotinoid) in standard solution and peach fruit. The Au@Ag NPs with 26 nm Au core size and 6 nm Ag shell thickness exhibited significant Raman enhancement, especially by the creation of hot spots through NPs aggregation induced by the connection between Au@Ag NPs and target molecules. The findings demonstrated that the characteristic wavenumber of the pesticides (thiacloprid, profenofos, and oxamyl) could be precisely identified using the SERS method. Compared with earlier studies, the current approach was rapid, inexpensive and without lengthy sample pretreatment. Moreover, the results revealed that the limit of detection (LOD) was 0.1 mg/kg for thiacloprid obtained in the peach extract with determination coefficient (R2) of 0.986. Additionally, LOD for both profenofos and oxamyl was 0.01 mg/kg with a determination coefficient (R2) of 0.985 and 0.988, respectively. Good recovery percentage (78.6-162.0%) showed the high SERS activity with better accuracy for the detection of the thiacloprid, profenofos, and oxamyl in peach. The results of this study could offer a promising SERS platform for simultaneous detection of other contaminants such as thiacloprid, profenofos and oxamyl in multifaceted food matrices.

Reductive transformation of profenofos with nanoscale Fe/Ni particles.

Profenofos is an abundantly used organophosphate pesticide in agriculture but its excessive use may lead to hazardous effects on environment. Thus, the present study focused on the reductive transformation of this pesticide in the presence of Fe/Ni bimetallic nanoparticles by optimizing the process parameters such as stirring time, nanoparticles dose, pH, and initial pesticide concentration. The results of reductive transformation were compared with photodegradation studies. It was found that with the increase in UV irradiation time, the percent degradation was increased. After 660 min, a 78% photodegradation of 100 µM solution of pesticide was observed. On increasing the initial pesticide concentration to 200 µM, the maximum degradation was achieved in 570 min, but here, only 73% degradation was observed. The rates of photodegradation observed with 100 to 400 µM solutions were 1.4 × 10-3, 1.5 × 10-3, 1.5 × 10-3, and 5 × 10-4 min-1 respectively.In case of reductive transformation carried out in the presence of Fe/Ni bimetallic nanoparticles, the degradation was observed to be increased from 78 to 93.9% in only 180 min. A further increase in pesticide concentration led to a decrease in degradation. Under these conditions, the rate of reaction was found to be 1.09 × 10-2 min-1. A 93% degradation of profenofos was further increased to 98% when the quantity of nanoparticles was increased twice; hence, a significant reduction in time of irradiation was observed. Reductive transformation of pesticide thus provided an efficient and cheaper method for reducing the burden of profenofos from the environment.

Covalent binding of the organophosphate insecticide profenofos to tyrosine on α- and ß-tubulin proteins.

Organophosphorus (OP) compounds can bind covalently to many types of proteins and form protein adducts. These protein adducts can indicate the exposure to and neurotoxicity of OPs. In the present work, we studied adduction of tubulin with the OP insecticide profenofos in vitro and optimized the method for detection of adducted peptides. Porcine tubulin was incubated with profenofos and was then digested with trypsin, followed by mass spectrometric identification of the profenofos-modified tubulin and binding sites. With solvent-assisted digestion (80% acetonitrile in digestion solution), the protein was digested for peptide identification, especially for some peptides with low mass. The MALDI-TOF-MS and LC-ESI-TOF-MS analysis results showed that profenofos bound covalently to Tyr83 in porcine α-tubulin (TGTY*83R) and to Tyr281 in porcine ß-tubulin (GSQQY*281R) with a mass increase of 166.02 Da from the original peptide fragments of porcine tubulin proteins. Tyrosine adduct sites were also confirmed by MALDI-TOF/TOF-MS analysis. This result may partially explain the neurotoxicity of profenofos at low doses and prolonged periods of exposure.

Specific phosphorothioate substitution within domain 6 of a group II intron ribozyme leads to changes in local structure and metal ion binding.

Group II introns are large self-splicing ribozymes that require high amounts of monovalent and divalent metal ions for folding and catalysis under in vitro conditions. Domain 6 of these ribozymes contains a highly conserved adenosine whose 2'-OH acts as a nucleophile during self-cleavage via the branching pathway. We have previously suggested a divalent metal ion that binds to the major groove at the GU wobble pair above the branch-A in a minimal, but active branch domain construct (D6-27) from the yeast mitochondrial intron Sc.ai5γ. Here we characterize metal ion binding to the phosphate oxygens at the branch site. In vitro transcription yielded a D6-27 construct where all R P oxygens of the uridine phosphate groups are replaced by sulfur (α-thio-D6-27). We determined its NMR structure, the second RNA-only structure containing thiophosphate groups. [31P] resonances were assigned and chemical shift changes monitored upon titration with Cd2+. In addition, the two uridines flanking the branch-point, U19 and U21 were specifically thioated by chemical synthesis (thio-U19-D6-27 and thio-U19/U21-D6-27), enabling us to study Cd2+ binding at the R P-, as well as the S P- position of the corresponding phosphate oxygens. Our studies reveal that both non-bridging phosphate oxygens of U19 are involved in metal ion coordination, whereas only the major groove phosphate oxygen of U21 is influenced. Together with NOE data of a hexaamminecobalt(III) titration, this suggests a single metal ion binding site at the GU wobble pair above the branch point in the major groove of D6 of this group II intron ribozyme.

Enantioselective apoptosis and oxidative damage induced by individual isomers of profenofos in primary hippocampal neurons.

The purpose of this study was to investigate the apoptosis-related cytotoxic effects and molecular mechanisms of individual isomers of profenofos (PFF) on primary hippocampal neurons at 1.0 to 20 mg L-1. The cell viability and lactate dehydrogenase (LDH) efflux indicated that (-)-PFF exposure was associated with more toxic effects than (+)-PFF above the concentration of 5 mg L-1 (P < 0.5). Flow cytometric results showed that the percentages of apoptotic cells incubated with 20 mg L-1 (-)-PFF, (+)-PFF and rac-PFF for 24 h reached 23.4%, 9.2% and 14.2% (P < 0.01), respectively. Hippocampal neurons incubated with (-)-PFF, (+)-PFF and rac-PFF exhibited a dose-dependent accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) and a dose-dependent inhibition of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, implying that the defense system of the tests induces oxidative damage. A statistically significant difference was observed between the two enantiomers at 5 mg L-1 and above. Moreover, the results showed that (-)-PFF exposure caused a significant loss in mitochondrial transmembrane potential (MMP), an upregulation of Ca2+ and Bax protein expression, a downregulation of Bcl-2 protein expression, and the activation of caspase-3 and caspase-9 in a dose-dependent manner; (+)-PFF and rac-PFF exhibited these effects to a lesser degree. All results suggest that PFF induced apoptosis in rat hippocampal neurons via the mitochondria-mediated pathway, and oxidative stress is one of the factors of PFF-induced apoptosis. In addition, (-)-PFF appears to play an important role in oxidative stress and apoptosis, indicating that enantioselectivity should be considered when assessing ecotoxicological effects and health risks of chiral pesticides.

Evaluation of cytotoxicity and genotoxicity of pesticide mixtures on lymphocytes.

The cytotoxicity and genotoxicity of pesticide mixtures viz. endosulfan + chlorpyrifos, chlorpyrifos + profenofos, and endosulfan + profenofos were evaluated on cultured human peripheral blood lymphocytes using assays for cell viability, and genotoxicity using chromosomal aberrations test and comet assay. The LC50 values for cytotoxicity were 3.50 µM, 4.18 µM, and 10.5 µM for profenofos, endosulfan, and chlorpyrifos respectively. When combined in equimolar concentrations, the LC50 values for cytotoxicity were 1.4 µM, 1.8 µM, and 2.0 µM for endosulfan + chlorpyrifos, chlorpyrifos + profenofos, and endosulfan + profenofos, respectively. Higher concentrations of individual pesticides (0.5-4.0 µM) but very low concentrations of pesticide mixtures caused significant DNA damage. Additive index values indicated a synergistic effect of toxicity for endosulfan + chlorpyrifos combination (1.12 TTU). The binary mixture of chlorpyrifos + profenofos showed an additive toxicity (0.46 TTU) while an antagonistic effect was observed for endosulfan + profenofos combination. Synergism could be due to these complementary pesticides simultaneously acting in different ways, magnifying their efficacy, whereas an additive interaction would imply that the chemicals are acting by the same mechanism and at the same target. Analysis of toxicity of pesticide mixtures may serve as important biomarker for occupational and household exposure to pesticides, with different modes of action.

[EXPERIMENTAL STUDY OF SPECIFIC ACTIVITY OF 1.3-DIAZINON-4 COM- POUND PYaTd1 DERIVATIVE IN VIVO].

AIM: Study anti-leprosy activity of.a 1.3-diazinon-4 compound derivative under the labora- tory code PYaTd1 on the model of intra-plantar infection of mice and evaluate the character of its antibacterial effect. MATERIALS AND METHODS: Study of specific activity was carried out in vivo on the experimental model of leprosy, proposed by Shepard C.C., that assumes execution of intraplantar infection of mice with a suspension of mycobacteria, produced from lepromas or autopsy tissue of a non-treated leprosy infected, or from tissues of experimental mice, previously infected with Mycobacterium leprae from non-treated patients. The study was carried out on 120 CBA line-mice infected with M.leprae (VIII passage) from patient M; Dapsone and PYaTdl compound were administered to animals next day after the infection with forage at a dose of 25 mg/kg for 4.5, 6, 9 and 11 months. The mice were split into 3 groups: control (infected.without treatment), com- parison (infected, receiving.dapsone), experimental (infected, receiving PYaTdl). After.the control term the mice were euthanized under chloroform anesthesia. Suspensions for quantification of mycobacteria were prepared from paw pads. Smears were stained by Ziehl-Nilsson. RESULTS: After 4.5 months the intensity of infect reproduction under, the effect of dapsone and PYaTd1 was reduced compared with control by 18 - 25 times. After a 6-mont course - by 50 - 75% and after 9 months - by 85 - 90%. After 11 months in mice that had received PYaTd1, an intensive suppression of microorganism reproduction as observed: the yield in paws was 70 times lower than in control. In the group that had received dapsone, a reduction of the number of mycobacteria by 20 - 25 times was detected, it was significantly less effective than under the conditions of PYaTd1 admnistration. CONCLUSION: A novel 1.3-diazinon- 4 derivative under the code PYaTd1 can actively supress reproduction of-M. leprae, that gives evidence regarding its specific anti-mycobacterial activity and determines perspectives of its further studies.

Fiber optic profenofos sensor based on surface plasmon resonance technique and molecular imprinting.

A successful approach for the fabrication and characterization of an optical fiber sensor for the detection of profenofos based on surface plasmon resonance (SPR) and molecular imprinting is introduced. Molecular imprinting technology is used for the creation of three dimensional binding sites having complementary shape and size of the specific template molecule over a polymer for the recognition of the same. Binding of template molecule with molecularly imprinted polymer (MIP) layer results in the change in the dielectric nature of the sensing surface (polymer) and is identified by SPR technique. Spectral interrogation method is used for the characterization of the sensing probe. The operating profenofos concentration range of the sensor is from 10(-4) to 10(-1)µg/L. A red shift of 18.7 nm in resonance wavelength is recorded for this profenofos concentration range. The maximum sensitivity of the sensor is 12.7 nm/log (µg/L) at 10(-4)µg/L profenofos concentration. Limit of detection (LOD) of the sensor is found to be 2.5×10(-6)µg/L. Selectivity measurements predict the probe highly selective for the profenofos molecule. Besides high sensitivity due to SPR technique and selectivity due to molecular imprinting, proposed sensor has numerous other advantages like immunity to electromagnetic interference, fast response, low cost and capability of online monitoring and remote sensing of analyte due to the fabrication of the probe on optical fiber.

Synthesis of bicoumarin thiophosphate derivatives as steroid sulfatase inhibitors.

Based on the frameworks of 7-hydroxy-2,3-dihydro-1H-cyclopenta[c]chromen-4-one, 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one and 3-hydroxy-8,9,10,11-tetrahydro-7H-cyclohepta[c]chromen-6-one, a series of bicoumarin thiophosphate analogs have been synthesized and biologically evaluated. Additionally, their binding modes have been modeled using docking techniques. The inhibitory properties of the synthesized compounds were tested against the STS isolated from human placenta. Most of the new STS inhibitors possessed good activities against STS. In particular, we found that the bis-(6-oxo-7,8,9,10-tetrahydro-6H-benzo[c]chromen-3-yl) hydrogenthiophosphate (10b) produced the largest inhibitory effect, with an IC50 value of 860 nM (an IC50 value of 1 µM for the 665-COUMATE used as a reference). The structure-activity relationships of the synthesized bicoumarin thiophosphate derivatives toward the STS enzyme have been discussed previously.

Dissipation of deltamethrin, triazophos, and endosulfan in ready mix formulations in tomato (Lycopersicon esculentum L.) and Egg plant (Solanum melongena L.).

Persistence of delltamethrin, endosulfan, and triazophos in egg plant and tomato was studied following application of two ready mix formulations of insecticides viz. deltametrhin and endosulfan (Cobra 5000; 0.75% deltamethrin + 29.5% endosulfan) and deltamethrin and triazophos (Annaconda Plus; 1% deltamethrin + 35% triazophos) at recommended (1.0 L/ha and double dose 2.0 L/ha). The residues of deltamethrin persisted till 7 and 5 days in tomato and egg plant fruits, respectively, in the ready mix formulation of Cobra 5000 whereas endosulfan persisted till 15 and 10 days in tomato and egg plant fruits, respectively. Dissipation of the insecticides followed first-order kinetics with half-life values of deltamethrin and endosulfan ranged from 2.6 to 4.7 and 1.4 to 1.7 days, respectively, for both the vegetables. In case of combination mix of deltamethrin and triazophos (Annaconda Plus), deltamethrin persisted beyond 5 days in both tomato and egg plant fruits, while triazophos persisted till 10 days in both the vegetables. Residues of deltamethrin and triazophos dissipated with half-life of 2.6-4.2 and 1.7-4.1 days, respectively, on tomato and egg plant fruits. Based on the Codex MRL limits, a safe waiting period of 5 and 3 days is suggested for tomato and egg plant, respectively, for the ready mix formulation of deltamethrin and endosulfan (Cobra 5000), and 5-day waiting period is suggested for tomato and egg plant for the combination mix of deltamethrin and triazophos.

Deciphering a nanocarbon-based artificial peroxidase: chemical identification of the catalytically active and substrate-binding sites on graphene quantum dots.

The design and construction of efficient artificial enzymes is highly desirable. Recent studies have demonstrated that a series of carbon nanomaterials possess intrinsic peroxidase activity. Among them, graphene quantum dots (GQDs) have a high enzymatic activity. However, the catalytic mechanism remains unclear. Therefore, in this report, we chose to decipher their peroxidase activity. By selectively deactivating the ketonic carbonyl, carboxylic, or hydroxy groups and investigating the catalytic activities of these GQD derivatives, we obtained evidence that the -C=O groups were the catalytically active sites, whereas the O=C-O- groups acted as substrate-binding sites, and -C-OH groups can inhibit the activity. These results were corroborated by theoretical studies. This work should not only enhance our understanding of nanocarbon-based artificial enzymes, but also facilitate the design and construction of other types of target-specific artificial enzymes.