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1.
Chemphyschem ; 24(1): e202200893, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594716

RESUMO

The front cover artwork is provided by Prof. Rainer Glaser's group at the Missouri University of Science and Technology. The image shows one of four potential energy surfaces generated from our rotation-inversion study of tertiary carbamates and highlights two of the eight possible transition state pathways between two ensembles of E- and Z-minima. In the context of synthetic studies of fluorinated carbamates R1 O-CO-N(R2 )CH2 CF3 , we unexpectedly observed two sets of 13 C NMR quartets for the CF3  group and we needed to understand their origin. Read the full text of the Research Article at 10.1002/cphc.2022005442.


Assuntos
Carbamatos , Isomerismo , Rotação , Espectroscopia de Ressonância Magnética/métodos
2.
J Enzyme Inhib Med Chem ; 38(1): 2169682, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36688444

RESUMO

A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The in vitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC50 values of 1.3 µM and 0.81 µM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1ß and NO. In addition, compound 3f presented significant neuroprotective effect on Aß25-35-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes in vitro and plasma. Furthermore, compound 3f could improve AlCl3-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD.


Assuntos
Doença de Alzheimer , Hidroxiquinolinas , Fármacos Neuroprotetores , Quinolinas , Animais , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Carbamatos/farmacologia , Peixe-Zebra , Inibidores da Colinesterase/farmacologia , Quinolinas/farmacologia , Desenho de Fármacos , Acetilcolinesterase/metabolismo , Relação Estrutura-Atividade , Estrutura Molecular
3.
J Chromatogr A ; 1689: 463744, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36610187

RESUMO

In food safety monitoring, on-site and simultaneous detection of a variety of insecticides with different concentrations in the same matrix is necessary. However, the task remains challenging. In this study, a novel nitrogen and sulfur co-doped carbon dot (N, S-CD) was synthesized and used as a QuEChERS clean-up reagent to reduce matrix interferences in the determination of insecticides in vegetables. In addition, a portable mass spectrometer (µ-MS) was employed, without chromatography separation, to directly determine neonicotinoids, carbamates, and benzopyrazole insecticides (with acetamiprid, imidacloprid, thiamethoxam, fipronil, and carbofuran as models) in the pretreated samples. The N,S-CD µ-MS method exhibited effective clean-up performance with satisfactory matrix effects between -15.2% and 15.7%. The recoveries of spiked vegetable samples ranged from 82.2% to 109.7% for the five target insecticides, and the relative standard deviations (RSDs) ranged from 3.8% to 16.5%. The linear ranges were from 2.0 to 5.0 ng/g, with low detection limits (LOD) from 0.5 to 1.0 ng/g. Moreover, the total pretreatment and detection time was within 20 min. Thus, the incorporation of N,S-CD with QuEChERS extraction, together with the portable µ-MS system, could be a promising and feasible strategy for on-site, rapid, and simultaneous detection of various insecticides in vegetables.


Assuntos
Inseticidas , Resíduos de Praguicidas , Inseticidas/análise , Verduras/química , Carbamatos/análise , Espectrometria de Massas em Tandem/métodos , Neonicotinoides/análise , Pirazóis , Resíduos de Praguicidas/análise , Cromatografia Líquida de Alta Pressão/métodos
4.
Chem Commun (Camb) ; 59(6): 764-767, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36541669

RESUMO

An efficient photoredox-catalyzed three-component coupling reaction of aryl sulfonium salts, carbon dioxide and amines has been developed for the first time. This reaction provides a new strategy for the synthesis of a range of valuable O-aryl carbamates from readily available arenes via a site-selective thianthrenation/carbamoyloxylation two-step process. Mild conditions, broad substrate scope and good functional group tolerance are the features of the transformation. The synthetic utility of the method was demonstrated by the late-stage modification of bioactive molecules and pharmaceuticals.


Assuntos
Aminas , Carbamatos , Dióxido de Carbono , Sais , Catálise
5.
Int J Biol Macromol ; 228: 273-285, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36581023

RESUMO

The development of synergistic drug combinations is a promising strategy for effective cancer suppression. Here, we report all-polysaccharide biodegradable polyelectrolyte complex hydrogels (DPCS) based on dextran phosphate carbamate (DP) and chitosan (CS) for controlled co-delivery of the anticancer drug doxorubicin (DOX) and the non-steroidal anti-inflammatory drug indomethacin (IND). IND can induce more apoptosis in tumor cells by reducing the level of multidrug resistance-associated protein 1. Based on calculations using density functional theory and zeta potential analysis data, carriers with high drug loading were obtained. The release profile of both drugs from the hydrogels was tuned by changing the molecular weight and functional groups content of the polysaccharides. The optimized DPCS showed a steady release of DOX both in vitro and in vivo, and a gradual release of IND, which constantly induced the action of DOX. Considering all of these benefits, DOX- and IND-loaded DPCS offer a promising long-acting polysaccharide-based antitumor platform.


Assuntos
Quitosana , Nanopartículas , Indometacina/farmacocinética , Portadores de Fármacos/farmacocinética , Carbamatos , Doxorrubicina/farmacocinética , Polissacarídeos/farmacologia , Hidrogéis
6.
Psychopharmacology (Berl) ; 240(1): 239-248, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36564670

RESUMO

Muscarinic acetylcholine receptors (mAChRs) have been shown to play significant roles in the regulation of normal cognitive processes in the hippocampus, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are also involved in these processes. This study aims to explore the mAChR-mediated regulation of AMPARs GluA2 trafficking and to reveal the key proteins and the signaling cascade involved in this process. Primary hippocampal neurons, as cell models, were treated with agonist 77-LH-28-1 and antagonist VU0255035, Fsc231, and APV. C57BL/6J male mice were stereotactically injected with 77-LH-28-1 and Fsc231 to obtain hippocampal slices. The trafficking of GluA2 was detected by surface biotinylation and immunostaining. Activation of M1 mAChRs promoted endocytosis and decreased the postsynaptic localization of the AMPA receptor subunit GluA2 and that phosphorylation of GluA2 at Ser880 was increased by M1 mAChR activity. Fsc231 blocked the endocytosis and postsynaptic localization of GluA2 induced by 77-LH-28-1 without affecting the phosphorylation of Ser880. PICK1 was required for M1 mAChR-mediated GluA2 endocytosis and downstream of phosphorylation of GluA2-Ser880, and the PICK1-GluA2 interaction was essential for M1 mAChR-mediated postsynaptic expression of GluA2. Taken together, our results show a functional correlation of M1 mAChRs with GluA2 and the role of PICK1 in their interplay. The schematic diagram for the modulation of GluA2 trafficking by M1 mAChRs. Activation of M1 mAChRs induces PKC activation, and the interaction of PICK1-GluA2 determines the endocytosis and postsynaptic localization of GluA2.


Assuntos
Receptor Muscarínico M1 , Receptores de AMPA , Camundongos , Animais , Masculino , Receptores de AMPA/metabolismo , Receptor Muscarínico M1/metabolismo , Camundongos Endogâmicos C57BL , Carbamatos , Hipocampo/metabolismo
7.
Eur J Med Chem ; 247: 115048, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36586299

RESUMO

Alongside reversible butyrylcholinesterase inhibitors, a plethora of covalent butyrylcholinesterase inhibitors have been reported in the literature, typically pseudo-irreversible carbamates. For these latter, however, most cases lack full confirmation of their covalent mode of action. Additionally, the available reports regarding the structure-activity relationships of the O-arylcarbamate warhead are incomplete. Therefore, a follow-up on a series of pseudo-irreversible covalent carbamate human butyrylcholinesterase inhibitors and the structure-activity relationships of the N-dialkyl O-arylcarbamate warhead are presented in this study. The covalent mechanism of binding was tested by IC50 time-dependency profiles, and sequentially and increasingly confirmed by kinetic analysis, whole protein LC-MS, and crystallographic analysis. Computational studies provided valuable insights into steric constraints and identified problematic, bulky carbamate warheads that cannot reach and carbamoylate the catalytic Ser198. Quantum mechanical calculations provided further evidence that steric effects appear to be a key factor in determining the covalent binding behaviour of these carbamate cholinesterase inhibitors and their duration of action. Additionally, the introduction of a clickable terminal alkyne moiety into one of the carbamate N-substituents and in situ derivatisation with azide-containing fluorophore enabled fluorescent labelling of plasma human butyrylcholinesterase. This proof-of-concept study highlights the potential of this novel approach and for these compounds to be further developed as clickable molecular probes for investigating tissue localisation and activity of cholinesterases.


Assuntos
Acetilcolinesterase , Butirilcolinesterase , Humanos , Butirilcolinesterase/metabolismo , Cinética , Acetilcolinesterase/metabolismo , Relação Estrutura-Atividade , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Carbamatos/farmacologia , Carbamatos/química
8.
Parasit Vectors ; 15(1): 484, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36550589

RESUMO

Organophosphate and carbamate insecticides have largely been used worldwide to control mosquito populations. As a response, the same amino acid substitution in the ace-1 gene (G119S), conferring resistance to both insecticides, has been selected independently in many mosquito species. In Anopheles gambiae, it has recently been shown that the G119S mutation is actually part of homogeneous duplications that associate multiple resistance copies of the ace-1 gene. In this study, we showed that duplications of resistance copies of the ace-1 gene also exist in the Culex pipiens species complex. The number of copies is variable, and different numbers of copies are associated with different phenotypic trade-offs: we used a combination of bioassays and competition in population cages to show that having more resistance copies conferred higher resistance levels, but was also associated with higher selective disadvantage (or cost) in the absence of insecticide. These results further show the versatility of the genetic architecture of resistance to organophosphate and carbamate insecticides around the ace-1 locus and its role in fine-tuned adaptation to insecticide treatment variations.


Assuntos
Anopheles , Culex , Inseticidas , Animais , Culex/fisiologia , Inseticidas/farmacologia , Inseticidas/metabolismo , Variações do Número de Cópias de DNA , Resistência a Inseticidas/genética , Alelos , Anopheles/genética , Carbamatos , Organofosfatos/farmacologia
9.
Acc Chem Res ; 55(24): 3616-3630, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36484500

RESUMO

The formation and study of molecules that model the sp-hybridized carbon allotrope, carbyne, is a challenging field of synthetic physical organic chemistry. The target molecules, oligo- and polyynes, are often the preferred candidates as models for carbyne because they can be formed with monodisperse lengths as well as defined structures. Despite a simple linear structure, the synthesis of polyynes is often far from straightforward, due in large part to a highly conjugated framework that can render both precursors and products highly reactive, i.e., kinetically unstable. The vast majority of polyynes are formed as symmetrical products from terminal alkynes as precursors via an oxidative, acetylenic homocoupling reaction based on the Glaser, Eglinton-Galbraith, and Hay reactions. These reactions are very efficient for the synthesis of shorter polyynes (e.g., hexaynes and octaynes), but yields often drop dramatically as a function of length for longer derivatives, usually starting with the formation of decaynes. The most effective approach to circumvent unstable precursors and products has been through the incorporation of sterically demanding end groups that serve to "protect" the polyyne skeleton. This approach was arguably identified in the early 1950s by Bohlmann and co-workers with the synthesis of tBu-end-capped polyynes. During the next 50 years, a polyyne with 14 contiguous alkyne units remained the longest isolated derivative until 2010, when the record was extended to 22 alkyne units. The record length was broken again in 2020, when a polyyne consisting of 24 alkynes was isolated and characterized. Beyond polyynes, there have been several reports describing the potential synthesis of carbyne, but conclusive characterization and proof of structure have been tenuous. The sole example of synthetic carbyne arises from synthesis within carbon nanotubes, when chains of thousands of sp carbon atoms have been linked to form polydisperse samples of carbyne. Thus, model compounds for carbyne, the polyynes, remain the best means to examine and predict the experimental structure and properties of this carbon allotrope.This Account will discuss the general synthesis of polyynes using homologous series of polyynes with up to 10 alkyne units as examples (decaynes). The limited number of specific syntheses of series with longer polyynes will then be presented and discussed in more detail based on end groups. The monodisperse polyynes produced from these synthetic efforts are then examined toward providing our best extrapolations for the expected characteristics for carbyne based on 13C NMR spectroscopy, UV-vis spectroscopy, X-ray crystallography, and Raman spectroscopy.


Assuntos
Nanotubos de Carbono , Poli-Inos , Humanos , Poli-Inos/química , Alcinos/química , Carbamatos
10.
PLoS One ; 17(12): e0279287, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36584091

RESUMO

Several methods have been reported to estimate Acetylcholinesterase (AChE) enzyme activity in blood samples. The Ellman assay is the most important among all but with several shortcomings, and there is a need to develop a method which is accurate, sensitive and quick for analyzing AChE. Therefore, we have developed an assay utilizing RP-HPLC with UV detection for the determination of AChE activity. This method measured the conversion of 1-naphthol acetate to 1-naphthol to estimate AChE activity in blood samples. Performance was judged on the basis of reproducibility, sensitivity, accuracy, and the ability to screen enzyme activity within 20minutes. A series of experiments were performed, varying the concentration of blood and substrate, with optimal sensitivity using 50 µM substrate and 10µL blood. The validation parameters such as linearity (R2 of ≥ 0.9842 for 1-naphthol and ≥ 0.9897 for 1-naphthol acetate), precision (94.21-96.41%), accuracy (85.2%-99.6% and 82.6%-99.3% for 1-naphthol and 1-naphthol acetate respectively), and robustness were validated according to International Conference on Harmonization (ICH) guidelines. Blood samples were collected from healthy people, farmers exposed to spraying of pesticides, and suicidal patients who ingested pesticides and were hospitalized and were analyzed by the developed method. The AChE level was approximately 21 units/mL compared to 24units/mL in controls, whereas suicidal patients showed the least AChE levels of 1 unit/mL. The employment of this method is recommended for estimating AChE level on various matrices.


Assuntos
Inseticidas , Praguicidas , Humanos , Inseticidas/toxicidade , Acetilcolinesterase , Organofosfatos , Inibidores da Colinesterase , Reprodutibilidade dos Testes , Cromatografia Líquida de Alta Pressão , Carbamatos
11.
Molecules ; 27(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36364153

RESUMO

Cenobamate (CNB) is the newest antiseizure medication (ASM) approved by the FDA in 2019 to reduce uncontrolled partial-onset seizures in adult patients. Marketed as Xcopri in the USA or Ontozry in the EU (tablets), its mechanism of action has not been fully understood yet; however, it is known that it inhibits voltage-gated sodium channels and positively modulates the aminobutyric acid (GABA) ion channel. CNB shows 88% of oral bioavailability and is responsible for modifying the plasma concentrations of other co-administered ASMs, such as lamotrigine, carbamazepine, phenytoin, phenobarbital and the active metabolite of clobazam. It also interferes with CYP2B6 and CYP3A substrates. Nowadays, few methods are reported in the literature to quantify CNB in human plasma. The aim of this study was to develop and validate, according to the most recent guidelines, an analytical method using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) to evaluate CNB dosage in plasma samples. Furthermore, we provided a preliminary clinical application of our methodology by evaluating the pharmacokinetic parameters of CNB in two non-adult patients. Plasma levels were monitored for two months. Preliminary data showed a linear increase in plasma CNB concentrations, in both patients, in agreement with the increase in CNB dosage. A seizure-free state was reported for both patients at the dose of 150 mg per day.


Assuntos
Clorofenóis , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Carbamatos/uso terapêutico , Convulsões/tratamento farmacológico
12.
Environ Sci Technol ; 56(23): 17188-17196, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36410104

RESUMO

The species sensitivity distribution (SSD) is an internationally accepted approach to hazard estimation using the probability distribution of toxicity values that is representative of the sensitivity of a group of species to a chemical. Application of SSDs in ecological risk assessment has been limited by insufficient taxonomic diversity of species to estimate a statistically robust fifth percentile hazard concentration (HC5). We used the toxicity-normalized SSD (SSDn) approach, (Lambert, F. N.; Raimondo, S.; Barron, M. G. Environ. Sci. Technol.2022,56, 8278-8289), modified to include all possible normalizing species, to estimate HC5 values for acute toxicity data for groups of carbamate and organophosphorous insecticides. We computed mean and variance of single chemical HC5 values for each chemical using leave-one-out (LOO) variance estimation and compared them to SSDn and conventionally estimated HC5 values. SSDn-estimated HC5 values showed low uncertainty and high accuracy compared to single-chemical SSDs when including all possible combinations of normalizing species within the chemical-taxa grouping (carbamate-all species, carbamate-fish, organophosphate-fish, and organophosphate-invertebrate). The SSDn approach is recommended for estimating HC5 values for compounds with insufficient species diversity for HC5 computation or high uncertainty in estimated single-chemical HC5 values. Furthermore, the LOO variance approach provides SSD practitioners with a simple computational method to estimate confidence intervals around an HC5 estimate that is nearly identical to the conventionally estimated HC5.


Assuntos
Poluentes Químicos da Água , Animais , Peixes , Invertebrados , Medição de Risco , Organofosfatos , Carbamatos , Especificidade da Espécie
13.
J Org Chem ; 87(23): 16115-16126, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36379008

RESUMO

Sulfoximines provide aza-analogues of sulfones, with potentially improved properties for medicinal chemistry. The sulfoximine nitrogen also provides an additional vector for the inclusion of other functionality. Here, we report improved conditions for rhodium catalyzed synthesis of sulfoximine (and sulfilimine) carbamates, especially for previously low-yielding carbamates containing π-functionality. Notably we report the preparation of propargyl sulfoximine carbamates to provide an alkyne as a potential click handle. Using Rh2(esp)2 as catalyst and a DOE optimization approach provided considerably increased yields.


Assuntos
Ródio , Ródio/química , Sulfóxidos/química , Carbamatos/química , Alcinos/química , Catálise
14.
J Forensic Leg Med ; 92: 102450, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36399917

RESUMO

Pesticides play a pivotal role in modern agricultural practices and effective domestic pest control. Despite their advantages, pesticides pose a great danger to humans and animals due to their toxicity. Pesticides, particularly carbamates, are extensively used all over the world in crop protection and domestic pest control, however, also causing morbidity and mortality on a larger scale, which is of great significance in both clinical and criminal justice management.Carbamates are derived from a carbamic acid (NH2COOH) that are commonly used as insecticides. Ethienocarb, Sevin, Carbaryl, Fenoxycarb, Furadan, Carbofuran, Aldicarb, and 2-(1-Methylpropyl) phenyl N-methylcarbamate are examples of insecticides that include the carbamate functional group. By reversibly inactivating the enzyme acetylcholinesterase, these insecticides can induce cholinesterase inhibition poisoning.Chromatographic methods, notably gas and liquid chromatography have traditionally been employed to analyse carbamate pesticides and their metabolites in various matrices. These approaches are employed due to their ability to separate the chemicals contained in a sample; as well as identify and quantify these compounds utilizing advanced detection systems. Aside from these GC and LC conventional methods, other detection and/or hyphenated techniques such as single-quadrupole, ion-trap, triple-quadrupole, or tandem mass spectrometry, have been used in carbamate analysis to provide quick results with excellent sensitivity, precision, and accuracy.The objective of this review is to describe various analytical techniques used to detect and determine carbamate pesticides in various matrices which include urine, blood, and tissues that are commonly encountered in emergency hospital laboratories and forensic science laboratories.


Assuntos
Carbamatos , Inseticidas , Praguicidas , Animais , Humanos , Acetilcolinesterase , Carbamatos/envenenamento , Carbaril/envenenamento , Carbofurano/envenenamento , Toxicologia Forense , Inseticidas/envenenamento , Praguicidas/envenenamento
15.
Anal Methods ; 14(45): 4659-4668, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36342027

RESUMO

Zeolitic imidazolate framework-8 modified magnetic halloysite nanotube (MHNTs@ZIF-8) composites were synthesized and evaluated for the first time as an efficient sorbent for the magnetic solid-phase extraction (mSPE) of carbamate pesticides (CPs) from water samples. MHNTs were prepared by coprecipitation, and MHNTs@ZIF-8 composites were assembled in situ at room temperature. After characterization, MHNTs@ZIF-8 was used to extract pirimicarb, propoxur, carbaryl, isoprocarb and fenobucarb via π-π stacking interaction and hydrophobic interaction between the imidazole skeleton of ZIF-8 and benzene rings or benzene-like rings in CPs, as well as the hydrogen bond formed between O in CPs and H in ZIF-8. The effects of the amount of sorbent, ionic strength, type and volume of desorption solvent and adsorption/desorption time were investigated. Under optimum conditions, good linearity was obtained for the analysis of CPs by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with R2 ≥ 0.9992. The limits of quantification range from 3 to 40 ng L-1 in water. Relative standard deviations (RSDs) were <7%, n = 5, within a batch and <9% among batches. The spiked recoveries were between 81 and 104%. The proposed method has been successfully applied to the determination of CPs in various water samples.


Assuntos
Nanotubos , Praguicidas , Poluentes Químicos da Água , Zeolitas , Cromatografia Líquida de Alta Pressão/métodos , Zeolitas/química , Espectrometria de Massas em Tandem/métodos , Argila , Benzeno/análise , Poluentes Químicos da Água/análise , Extração em Fase Sólida/métodos , Praguicidas/análise , Carbamatos/análise , Ésteres , Nanotubos/análise , Água/análise , Fenômenos Magnéticos
16.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 40(10): 785-786, 2022 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-36348564

RESUMO

The incidence of carbamate insecticide poisoning has increased gradually in recent years, and anticholinergic drugs are the specific antidotes. In 2020, the Peking University Third Hospital admitted a patient with carbamate insecticide poisoning, whose main clinical manifestations were dizziness, vomiting and blurred vision. During the treatment with penehyclidine hydrochloride, the patient developed delirium. This paper retrospectively analyzed the clinical data and treatment process of the patient to improve people's understanding of the side effects of penhyclidine hydrochloride in the treatment of insecticide poisoning.


Assuntos
Delírio , Inseticidas , Intoxicação por Organofosfatos , Intoxicação , Humanos , Estudos Retrospectivos , Ácido Clorídrico , Carbamatos/uso terapêutico , Intoxicação/terapia , Intoxicação por Organofosfatos/tratamento farmacológico
17.
Se Pu ; 40(12): 1064-1075, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36450346

RESUMO

In order to monitor the risk of pesticide pollutants in drinking water, an analytical method based on online-solid phase extraction coupled with ultra performance liquid chromatography-triple quadrupole mass spectrometry (online-SPE-UPLC-MS/MS) was established for the simultaneous rapid screening and determination of 107 pesticides and metabolites (organophosphorus, organic nitrogen, organic heterocycle, carbamate, amide, benzoyl urea, neonicotinoid, etc.) in raw water and drinking water. Different injection volumes (5, 10, and 15 mL) were compared. The detection response increased with an increase in the injection volume, but the matrix effect also became more pronounced. Under the premise of ensuring the sensitivity of the method and meeting the detection requirements, the injection volume was selected as 5 mL. Accordingly, the samples were filtered through a 0.22-µm hydrophilic polytetrafluoroethylene filter, and then, 5 mL samples were injected into the online-SPE system by the automatic sampler. After adsorption on an X Bridge C18 online-SPE column, the samples were washed with pure water and eluted by gradient elution using acetonitrile and 0.1% formic acid aqueous solution as the mobile phases, with separation on an ACQUITY HSS T3 column. The samples were detected by multiple reaction monitoring with electrospray ionization in positive and negative ion modes, and quantified by an external standard method. Using raw water and drinking water as the sample matrices, the accuracy and precision of the method were verified. The 107 pesticides and metabolites showed good linear relationships in different ranges with correlation coefficients (r2)>0.995. The limits of detection (LODs, S/N=3) of the method were 0.03-1.5 ng/L, and the limits of quantification (LOQs, S/N=10) were 0.1-5.0 ng/L. The target pesticides were spiked at concentration levels of 1, 20, and 50 ng/L. The spiked recoveries of the 107 targets in raw water and drinking water samples were 60.6%-119.8% and 61.2%-119.0%, respectively. The corresponding relative standard deviations (RSDs, n=6) were 0.3%-18.6% and 0.4%-17.1%. The pesticide residues in raw water and drinking water were determined by this method. Amide herbicides, triazine herbicides, triazole insecticides, carbamate insecticides, and neonicotinoid insecticides had high detection rates. The detected concentrations ranged from 0.1 to 97.1 ng/L in raw water and from 0.1 to 93.6 ng/L in drinking water. The sample consumption of online-SPE method was lower than that in the traditional off-line SPE methods, which greatly improved the convenience of sample collection, storage, and transportation. The samples only need to be filtered before injection and analysis. The method is simple to operate and shows good reproducibility. With this online-SPE method, only 23 min were required from online enrichment to detection completion. The developed method has the advantages of high analytical speed and high sensitivity. The method is suitable for the trace analysis and determination of 107 typical pesticides in raw water and drinking water, which effectively improves the detection efficiency of pesticides in water and has high potential for practical application. It can extend technical support for the pollution-level analysis of typical pesticides and metabolites in drinking water and provide an objective basis for human health risk assessment.


Assuntos
Água Potável , Herbicidas , Inseticidas , Praguicidas , Humanos , Cromatografia Líquida , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Extração em Fase Sólida , Carbamatos , Neonicotinoides , Amidas
18.
Int J Mol Sci ; 23(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36361960

RESUMO

Bifenazate is a novel acaricide that has been widely used to control spider mites. Interestingly, we found bifenazate had a biological activity against the diamondback moth (Plutella xylostella), one of the most economically important pests on crucifer crops around the world. However, the molecular mechanisms underlying the response of P. xylostella to bifenazate treatment are not clear. In this study, we first estimated the LC30 dose of bifenazate for third-instar P. xylostella larvae. Then, in order to identify genes that respond to the treatment of this insecticide, the comparative transcriptome profiles were used to analyze the gene expression changes in P. xylostella larvae after exposure to LC30 of bifenazate. In total, 757 differentially expressed genes (DEGs) between bifenazate-treated and control P. xylostella larvae were identified, in which 526 and 231 genes were up-regulated and down-regulated, respectively. The further Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the xenobiotics metabolisms pathway was significantly enriched, with ten detoxifying enzyme genes (four P450s, five glutathione S-transferases (GSTs), and one UDP-Glucuronosyltransferase (UGT)) were up-regulated, and their expression patterns were validated by qRT-PCR as well. Interestingly, the present results showed that 17 cuticular protein (CP) genes were also remarkably up-regulated, including 15 CPR family genes. Additionally, the oxidative phosphorylation pathway was found to be activated with eight mitochondrial genes up-regulated in bifenazate-treated larvae. In contrast, we found some genes that were involved in tyrosine metabolism and purine pathways were down-regulated, indicating these two pathways of bifenazate-exposed larvae were significantly inhibited. In conclusion, the present study would help us to better understand the molecular mechanisms of sublethal doses of bifenazate detoxification and action in P. xylostella.


Assuntos
Mariposas , Animais , Mariposas/genética , Mariposas/metabolismo , Perfilação da Expressão Gênica , Carbamatos , Hidrazinas/metabolismo , Transcriptoma , Larva/genética
19.
PLoS One ; 17(10): e0275825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36240161

RESUMO

BACKGROUND: Malaria remains a public health challenge in endemic countries of the world. The use of Long-lasting Insecticidal Nets (LLINs) is one of the major ways of malaria vector control. Recent evidence however suggests some LLINs are unable to maintain their effectiveness over their useful life span. This study assessed the bio-efficacy, physical integrity, use and attrition at 6 and 12-months post-distribution of LLINs (LifeNet). METHODS: Following a mass distribution of LLINs in the West Mamprusi District of the North-East region of Ghana in 2018, a total of 147 LLINs were sampled for physical integrity and attrition assessment using hole size and the number of holes as a measure of the proportionate hole index (pHI). Bioassays were conducted on sixty randomly selected LLINs using the WHO guidelines for bio-efficacy testing (cone tests), (20 each at baseline, midline and endline) over a one-year study period. Bed net ownership and use as well as malaria vector resistance status were also assessed. RESULTS: Findings indicate high bio-efficacy of approximately 100% average mortalities of mosquitoes at baseline, 6-months and 12-months post-distribution. A small proportion of LLINs (0.8% and 5.6% at the 6 and 12-months surveys respectively) were damaged beyond maintenance while 62.4% and 62.7% of LLINs were used the night before the survey for 6 and 12-months post-distribution respectively. Households with electricity were less likely to use LLINs compared to those without electricity (P-value = 0.016, OR = 0.39). There were 20 fewer LLINs recovered at the 12-months relative to the 6-months resulting in 14.3% attrition rate. Susceptibility testing showed high pyrethroid and organochlorine resistance (18%, 67.5% and 3.8%) to local malaria vectors respectively), whereas organophosphates and carbamates recorded vector susceptibility of 100% for pirimiphos-methyl and 98.7% for bendiocarb. CONCLUSION: Biological efficacy, physical integrity and net attrition during the study period were in conformity with respect to the WHOPES one year net use. LLINs remained effective after one-year of usage. Net ownership was high in the study households. There should be continuous and regular distribution campaigns to maintain high coverage.


Assuntos
Anopheles , Mosquiteiros Tratados com Inseticida , Inseticidas , Malária , Piretrinas , Animais , Carbamatos , Gana/epidemiologia , Humanos , Malária/epidemiologia , Malária/prevenção & controle , Controle de Mosquitos/métodos , Mosquitos Vetores , Organofosfatos
20.
J Org Chem ; 87(21): 13615-13626, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36263722

RESUMO

Synthetic methods of unnatural α-amino acids have always been the focus of extensive research due to their significant bioactivities. However, convenient transition-metal-free catalyzed methods are still in demand. Herein, we report a novel strategy for the construction of an unnatural α-amino acid skeleton via intramolecular rearrangement of carbamates, which are readily available from amines and their common protecting groups. This rearrangement could afford a variety of amino ester products in up to 98% yield, even in gram-scale reaction. The reaction mechanism was studied in detail through experiments and theoretical calculations. The complex-induced proximity effect (CIPE) from the 2-pyridyl group is shown to be indispensable for this transformation.


Assuntos
Aminoácidos , Carbamatos , Carbamatos/química , Aminoácidos/química , Aminas/química , Ésteres
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