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1.
Food Chem ; 313: 126027, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31923865

RESUMO

Tetrabromobisphenol A (TBBPA) and Hexabromocyclododecanes (HBCDs) are commonly used as brominated flame retardants in large volumes, and accumulate in plants and animals in the environment, and people are exposed to them when consuming food. As many countries are monitoring them in food, it is necessary to develop a method to analyze them simultaneously for cost efficiency. A method was developed and optimized under different conditions using accelerated solvent extraction to extract the lipids from the samples, acid silica column to clean the samples and liquid chromatography coupled with tandem mass spectrometry to determine TBBPA and HBCDs. The method was validated in different kinds of food. Uncertainty of measurement was calculated by combining all uncertainties of contributors. Intermediate precision (reproducibility) was the most influential contributor to uncertainty. 5 food categories with 115 samples were analyzed with the method, and mackerels containing high level of fat were highly contaminated by TBBPA and HBCDs.


Assuntos
Análise de Alimentos/métodos , Hidrocarbonetos Bromados/análise , Bifenil Polibromatos/análise , Animais , Cromatografia Líquida de Alta Pressão , Retardadores de Chama/análise , Hidrocarbonetos Bromados/química , Carne/análise , Alimentos Marinhos/análise , Espectrometria de Massas em Tandem
2.
Chemosphere ; 240: 124813, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31542576

RESUMO

Hexabromocyclododecane (HBCDD) has frequently been detected in wildlife. However, there is limited research on its bioaccumulation and biomagnification in insect-dominated aquatic and terrestrial food webs. This study investigated the occurrence of HBCDD in insects and their predators collected from a former e-waste contaminated pond and its surrounding region. The concentrations of Æ©HBCDD (sum concentrations of α-, ß-, and γ-HBCDDs) ranged from nd to 179 ng g-1 lipid weight. α-HBCDD was the predominant diastereoisomer in all biotic samples, and the contribution of α-HBCDD was higher in predators than in prey insects. A significantly positive linear relationship was found between Æ©HBCDD concentrations (lipid weight) and trophic levels based on δ15N in aquatic organisms (p < 0.05), while trophic dilution was observed in the terrestrial food web. This result indicates an opposite trophic transfer tendency of HBCDD in terrestrial and aquatic ecosystems. The biomagnification factor (BMF) for α-HBCDD was higher in terrestrial birds (2.03) than in frogs (0.29), toads (0.85), and lizards (0.63). This may be due to differences between poikilotherms and homeotherms in terrestrial ecosystems.


Assuntos
Resíduo Eletrônico/efeitos adversos , Hidrocarbonetos Bromados/química , Insetos/patogenicidade , Animais , Bioacumulação , China , Ecossistema , Resíduo Eletrônico/análise , Cadeia Alimentar , Humanos
3.
Chem Commun (Camb) ; 55(61): 8959-8962, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31290487

RESUMO

Hydrocarbon stapled peptides are promising therapeutics for inhibition of intracellular protein-protein interactions. Here we develop a new high-throughput strategy for hydrocarbon stapled peptide discovery based on mRNA display of peptides containing α-methyl cysteine and cyclized with m-dibromoxylene. We focus on development of a peptide binder to the HPV16 E2 protein.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Evolução Molecular Direcionada/métodos , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Peptídeos/metabolismo , Engenharia de Proteínas/métodos , Fatores de Transcrição/metabolismo , Alquilação , Sequência de Aminoácidos , Proteínas de Ciclo Celular , Ciclização , Cisteína/química , Hidrocarbonetos Bromados/química , Biblioteca de Peptídeos , Peptídeos/química , Ligação Proteica/efeitos dos fármacos , RNA Mensageiro/química
4.
Ecotoxicol Environ Saf ; 181: 321-329, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31202932

RESUMO

In this study, the levels and distribution patterns of HBCD diastereoisomers in air, water, soil, and sediment samples in South Korea were investigated after optimizing the UPLC-MS/MS analytical process. Extraction and cleanup efficiencies were tested using several different extraction solvents and adsorbents. Dichloromethane was selected as the base extraction solvent, and multi-layer silica gel (MSG) and MSG-alumina columns were selected for the removal of HBCDs from complex environmental matrices. The concentration of Æ©3 HBCDs was 22-133 pg/m3, 10-128 ng/g, 0.2-151 ng/L, and 0.5-552 ng/g dw for air, soil, water, and sediment samples, respectively. Relatively higher concentrations of Æ©3 HBCDs were observed at stations adjacent to industrial facilities (e.g., rubber and plastic, textile, chemical, fabricated metal, and wholesale trade factories) associated with the use of commercial HBCDs. The proportion of γ-HBCD in the soil (48.3-86.2%) and sediment (54.2-78.1%, except for one station) samples was similar to that found in technical and commercial HBCDs. In contrast, α-HBCD (52.3-71.2%) was dominant in all air samples, while the water samples displayed no clear trend in their diastereoisomer profiles. As the first nationwide report on HBCD diastereoisomers in the environment, this study demonstrates that most environmental compartments in South Korea are moderately contaminated with HBCDs.


Assuntos
Poluentes Atmosféricos/análise , Sedimentos Geológicos/química , Hidrocarbonetos Bromados/análise , Poluentes do Solo/análise , Poluentes Químicos da Água/análise , Poluentes Atmosféricos/química , Cromatografia Líquida , Monitoramento Ambiental/métodos , Retardadores de Chama/análise , Hidrocarbonetos Bromados/química , República da Coreia , Poluentes do Solo/química , Estereoisomerismo , Espectrometria de Massas em Tandem , Poluentes Químicos da Água/química
5.
Molecules ; 24(9)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083344

RESUMO

The intermolecular interaction in difluoromethane, dichloromethane, dibromomethane, and diiodomethane dimers has been investigated using high level quantum chemical methods. The potential energy curve of intermolecular interaction along the C⋯C bond distance obtained using the coupled-cluster theory with singles, doubles, and perturbative triples excitations CCSD(T) were compared with values given by the same method, but applying the local (LCCSD(T)) and the explicitly correlated (CCSD(T)-F12) approximations. The accuracy of other theoretical methods-Hartree-Fock (HF), second order Møller-Plesset perturbation (MP2), and dispersion corrected DFT theory-were also presented. In the case of MP2 level, the canonical and the local-correlation cases combined with the density-fitting technique (DF-LMP2)theories were considered, while for the dispersion-corrected DFT, the empirically-corrected BLYP-D and the M06-2Xexchange-correlation functionals were applied. In all cases, the aug-cc-pVTZ basis set was used, and the results were corrected for the basis set superposition error (BSSE) using the counterpoise method. For each molecular system, several dimer geometries were found, and their mutual orientations were compared with the nearest neighbor orientations obtained in recent neutron scattering studies. The nature of the intermolecular interaction energy was discussed.


Assuntos
Compostos Inorgânicos/análise , Compostos Inorgânicos/química , Dimerização , Hidrocarbonetos Bromados/análise , Hidrocarbonetos Bromados/química , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/química , Hidrocarbonetos Fluorados/análise , Hidrocarbonetos Fluorados/química , Hidrocarbonetos Iodados/análise , Hidrocarbonetos Iodados/química , Modelos Químicos , Modelos Moleculares , Teoria Quântica
6.
Chemosphere ; 229: 77-85, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31075705

RESUMO

In this study the direct and indirect photolysis of the novel brominated flame retardant 2,4,6-Tris-(2,4,6-tribromophenoxy)-1,3,5-triazine (TTBP-TAZ) in an organic solvent mixture (60:30:10, ACN:MeOH:THF) under UV-(C) and simulated sunlight irradiation was investigated, and the formed photo-transformation products were identified for the first time. TTBP-TAZ was almost completely degraded within 10 min under UV-(C) irradiation. Due to the fast degradation no specific kinetic order could be observed. In comparison, the reaction under simulated sunlight irradiation was much slower and thus, the kinetic first-order could be determined. The observed photolysis rate constant k as well as the half-life time t1/2 were estimated to be k = (0.0163 ±â€¯0.0002) h-1 and t1/2 = 42.3 h, respectively. The addition of 2-propanol and hydrogen peroxide to investigate the influence of indirect photolysis under UV-(C) irradiation causes no influence on the degradation of TTBP-TAZ. Nevertheless, the removal of TTBP-TAZ under UV-(C) and simulated sunlight without additional chemicals (except solvent) indicates that the direct photolysis plays a significant role in the degradation mechanism of TTBP-TAZ. In both irradiation experiments, TTBP-TAZ was quantitatively degraded that involve the formation of previously unknown PTPs. Overall, two main PTPs were determined when irradiated with UV-(C) and eight sequential debromination products were observed when irradiated by simulated sunlight. These were determined by HPLC-DAD and - MS/(MS), respectively. Based on the chosen experimental conditions the consecutive debromination as well as photo-Fries rearrangement was confirmed as the main degradation pathway by high resolution mass spectrometry and X-ray diffraction.


Assuntos
Retardadores de Chama/análise , Halogenação/fisiologia , Hidrocarbonetos Bromados/química , Triazinas/química , Cinética , Fotólise
7.
J Chromatogr A ; 1600: 95-104, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31056271

RESUMO

Halogen bonding (XB) was here proposed, for the first time, as a solubilization mechanism for increasing efficiency in the liquid-liquid microextraction of halogenated compounds. The approach was illustrated by the extraction of hexabromocyclododecane (HBCD) enantiomers in natural waters with a supramolecular solvent (SUPRAS) made up of inverted hexagonal aggregates of decanoic acid. The XB and dispersion interactions offered by the SUPRAS were able to extract the six HBCD enantiomers (i.e. (+)-α-, (-)-α- (+)-ß-, (-)-ß-, (+)-γ- and (-)-γ-) quantitatively (e.g. recoveries in the range 89-106%) and reach concentration factors as high as 720 without the need for solvent evaporation. HBCD enantiomers in the SUPRAS extract were directly analysed by chiral liquid chromatography coupled to tandem mass spectrometry (LCMS/MS). Quantitation limits of the method (0.09-0.9 ng L-1) were below the quality standard stablished by the European Union for HBCDs in inland surface water samples (1.6 ng L-1), and the precision, expressed as relative standard deviation (n = 6), was below 9% for all the HBCD enantiomers at concentrations within the range 50-500 ng L-1. The method was successfully applied to the enantioselective determination of HBCDs in the dissolved and the particle-bound fractions of river waters containing different concentration of suspended particles (10-57.8 mg L-1) that were spiked at two concentration levels (10 and 100 ng L-1). The results here obtained prove that XB is a valuable mechanism for the solubilisation of halogenated compounds that can effectively increase their recovery from liquid and solid samples.


Assuntos
Monitoramento Ambiental/métodos , Hidrocarbonetos Bromados/isolamento & purificação , Microextração em Fase Líquida/métodos , Rios/química , Poluentes Químicos da Água/isolamento & purificação , Cromatografia Líquida , Halogênios/química , Hidrocarbonetos Bromados/química , Solventes/química , Estereoisomerismo , Espectrometria de Massas em Tandem , Poluentes Químicos da Água/análise
8.
Ecotoxicol Environ Saf ; 179: 96-103, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31026755

RESUMO

Chloroperoxidase (CPO) is a hybrid of two different families of enzymes, peroxidases and P450s. However, it is poorly understood on CPO's multiple catalytic functions. Herein, phenol was selected as a model substrate to investigate the multiple catalytic roles of CPO. Results showed that phenol was readily transformed into a variety of brominated organic compounds (BOCs) via the CPO-mediated oxidative process. A total of 16 BOCs were identified using gas and liquid chromatography coupled with mass spectrometry. Possible reaction pathways could be attributable to four CPO-mediated processes, including bromination, radical coupling, intramolecular cyclization and debromination. Higher bromide concentrations and lower pH conditions both facilitated the formation of brominated products. While a higher bromination capacity was observed in pH 3.0 solutions, CPO-mediated radical couplings were more favorable at pH 5.0 and 6.0. Although CPO might catalyze chlorination when chloride and bromide coexisted in the solution, BOCs were the dominant products of CPO-mediated phenol oxidation. Results of this study suggest that various catalytic roles of CPO may contribute to the biotic formation of BOCs in the natural environment.


Assuntos
Brometos/química , Cloreto Peroxidase/química , Hidrocarbonetos Bromados/química , Fenol/química , Catálise , Cromatografia Líquida , Halogenação , Estrutura Molecular , Oxirredução , Espectrometria de Massas em Tandem
9.
Chemosphere ; 226: 238-245, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30928716

RESUMO

The individual degradation rates of the three dominant stereoisomers (α, ß, γ) of hexabromocyclododecane (HBCDD) with bisulfide and polysulfides were investigated at pH 9 in methanol/water solutions at two different temperatures (25 °C and 40 °C). Under all conditions investigated, α-HBCDD reacts 10 to 20 times slower with bisulfide than ß-HBCDD and γ-HBCDD. The difference in reactivity of HBCDD isomers can be explained by the different populations of stable conformers with large dihedral angle between the vicinal bromine atoms. It was also observed that the reaction of HBCDD with polysulfides is about six times faster than with bisulfide. The experiments performed in solvent mixtures with increased water content at 40 °C indicated that the reaction of HBCDD with bisulfide is faster with higher percentage of water. The much slower abiotic reaction of α-HBCDD compared to ß-HBCDD and γ-HBCDD could potentially contribute to the fact that α-HBCDD is more persistent in the environment than γ-HBCDD. Only one isomer of tetrabromocyclododecene (TBCDe-5) was identified as a degradation product of the reaction of HBCDD with reduced sulfur species. TBCDe-5 itself reacts about ten times slower with bisulfide and twenty times slower with polysulfide than HBCDD. The study demonstrates that polysulfides and bisulfides can reduce HBCDD sufficiently in natural anoxic environments and the dominant pathway for the degradation of HBCDD by reduced sulfur species is very likely to be the reductive debromination of vicinal dibromides via concerted anti-elimination.


Assuntos
Hidrocarbonetos Bromados/química , Estereoisomerismo , Enxofre/química , Metanol/química , Substâncias Redutoras , Sulfetos/química , Água/química , Poluentes Químicos da Água/análise
10.
Chemosphere ; 227: 329-333, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30999173

RESUMO

Brominated flame retardants are often associated with adverse environmental effects. Nevertheless, these chemicals are required in order to comply with fire safety standards. Therefore, a better environmental profile is desirable. A "new" class of flame retardants is claimed to fulfil this request while still being feasible for established industrial processes. Different to previous brominated flame retardants, this new group is based on a polymeric structure that could indeed lead to a better environmental profile. However, not much is known about the long-term behaviour of such flame retardants. This short review summarizes what has already been published. With an annual production volume of 26,000 metric tons, "Polymeric FR" is currently the only industrially produced representative of this group. It has been shown to degrade under specific circumstances (following UV and heat exposure). Detected degradation products cause almost no acute toxicity, whereas chronic toxicity might be relevant. Nevertheless, as long as polymeric flame retardants are only used in building insulation, the actual risk seems to be rather limited.


Assuntos
Retardadores de Chama/metabolismo , Hidrocarbonetos Bromados/química , Polímeros , Materiais de Construção , Hidrocarbonetos Bromados/análise
11.
Chemosphere ; 227: 570-579, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31004823

RESUMO

In this study, the acute and subchronic toxicity of 1-alkyl-3-methyl imidazole bromide ionic liquids (ILs) [Cnmim]Br (n = 2, 4, 6, 10, 12) was evaluated utilizing earthworms (Eisenia fetida) as a basis for their impact on terrestrial ecosystems. The filter paper tests and artificial soil tests were conducted as acute toxicity tests to investigate the LC50 of ILs, while in subchronic toxicity tests, earthworms were exposed to ILs in artificial soil (5, 10, 20 and 40 mg kg-1) for 28 d. Reactive oxygen species (ROS), antioxidant enzymes, detoxifying enzymes and oxidative damage were measured to determine subchronic effects of ILs on E. fetida. The results showed that when the earthworms were exposed to these five ILs in acute toxicity experiments, [C2mim]Br had the lowest toxicity, as the alkyl length increased, the toxicity increased up to [C10mim]Br: a "cut-off effect" (decreased toxicity) was observed at [C12mim]Br. The results highlight the varying toxicity of ILs with different alkyl chains to E. fetida and provide valuable data for detailing the impact of ILs on ecological receptors.


Assuntos
Dano ao DNA , Hidrocarbonetos Bromados/toxicidade , Imidazóis/toxicidade , Líquidos Iônicos/toxicidade , Oligoquetos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Hidrocarbonetos Bromados/química , Imidazóis/química , Inativação Metabólica , Líquidos Iônicos/química , Dose Letal Mediana , Oligoquetos/genética , Oligoquetos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade Aguda
12.
Chemosphere ; 226: 744-754, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30965245

RESUMO

Short-chain chlorinated paraffins (SCCPs) are polyhalogenated hydrocarbons as are hexachlorocyclohexanes (HCHs) and hexabromocyclododecanes (HBCDs). They all have been classified as persistent organic pollutants (POPs) under the UN Stockholm Convention. Per se such compounds are transformed slowly in the environment, transported over long distances and accumulate in biota. Several Sphingomonadacea strains isolated from HCH dump sites have evolved to express enzymes that can transform HCHs and HBCDs. We hypothesized that LinA2, a dehydrohalogenase expressed in such bacteria, may also transform CPs to chlorinated olefins (COs). Three mixtures of penta- to deca-chlorinated undecanes (C11), dodecanes (C12) and tridecanes (C13) were exposed to LinA2. High-resolution full-scan mass spectra (R∼8'000) of CPs and COs were obtained applying a soft ionization method, enhancing chloride-adduct [M+Cl]- formation. A mathematical deconvolution procedure was used to separate interfering spectra to verify that LinA2 indeed catalyzed the conversion of CPs to COs. About 20-40% of the material was transformed in 24 h, about 50-70% was converted in 200 h. A bimodal first-order kinetic model could describe transformations of reactive and persistent CPs. Under the given conditions reactive CPs (τ1/2 = 1.4-6.9 h) were converted 30 to 190-times faster than the persistent ones (τ1/2 = 150-260 h). Proportions of persistent isomers (pp) varied from 60 to 80%. Lower chlorinated homologues contained higher proportions of persistent isomers. In conclusion, SCCP mixtures contain both, material that is readily converted by LinA2, and persistent material that is not or only slowly transformed.


Assuntos
Biotransformação/genética , Monitoramento Ambiental/métodos , Halogenação/genética , Hexaclorocicloexano/química , Hidrocarbonetos Bromados/química , Hidrolases/química , Parafina/química
13.
Molecules ; 24(5)2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30866543

RESUMO

Neuronal nicotinic acetylcholine receptors are cell membrane-bound ion channels that are widely distributed in the central nervous system. The α4ß2 subtype of neuronal nicotinic acetylcholine receptor plays an important role in modulating the signaling pathways for pain. Previous studies have shown that agonists, partial agonists, and positive allosteric modulators for the α4ß2 receptors are effective in relieving pain. Desformylflustrabromine is a compound that acts as an allosteric modulator of α4ß2 receptors. The aim of this study was to assess the effects of desformylflustrabromine on chemically induced pain. For this purpose, the formalin-induced pain test and the acetic acid-induced writhing response test were carried out in CD-1 mice. Both tests represent chemical assays for nociception. The results show that desformylflustrabromine is effective in producing an analgesic effect in both tests used for assessing nociception. These results suggest that desformylflustrabromine has the potential to become a clinically used drug for pain relief.


Assuntos
Analgésicos/administração & dosagem , Hidrocarbonetos Bromados/administração & dosagem , Alcaloides Indólicos/administração & dosagem , Dor/tratamento farmacológico , Receptores Nicotínicos/metabolismo , Ácido Acético/efeitos adversos , Regulação Alostérica , Analgésicos/química , Analgésicos/farmacologia , Animais , Formaldeído/efeitos adversos , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/farmacologia , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Masculino , Camundongos , Estrutura Molecular , Dor/induzido quimicamente
14.
ACS Comb Sci ; 21(2): 69-74, 2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30615417

RESUMO

DNA-encoded library technology (ELT) has emerged in the pharmaceutical industry as a powerful tool for hit and lead generation. Over the last 10 years, a number of DNA-compatible chemical reactions have been published and used to synthesize libraries. Among the most commonly used reactions in medicinal chemistry is the C-N bond formation, and its application to DNA-encoded library technology affords an alternative approach to identify high-affinity binders for biologically relevant protein targets. Herein we report a newly developed Pd-promoted C-N cross coupling reaction between DNA-conjugated aryl bromides and a wide scope of arylamines in good to excellent yields. The mild reaction conditions should facilitate the synthesis of novel DNA-encoded combinatorial libraries.


Assuntos
Aminas/química , DNA/química , Hidrocarbonetos Aromáticos/química , Hidrocarbonetos Bromados/química , Compostos Organometálicos/química , Paládio/química , Catálise , Técnicas de Química Combinatória/métodos , Bibliotecas de Moléculas Pequenas/química
15.
J Asian Nat Prod Res ; 21(6): 573-578, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30612465

RESUMO

A new brominated polyacetylene xestonariene J (1), bearing a rare 2,4-dibromo-1-ene-3-yne terminal in the molecule, along with two known related analogues (2 and 3), was obtained from Chinese marine sponge Xestospongia testudinaria. Its structure was determined on the basis of detailed spectroscopic analysis and comparison with literature data.


Assuntos
Hidrocarbonetos Bromados/química , Polienos/química , Poli-Inos/química , Poríferos/química , Animais , China , Estrutura Molecular
16.
Chem Biodivers ; 16(1): e1800451, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30394674

RESUMO

Omaezallene derivatives (nor-bromoallene, nor-bromodiene, and bromoenynes) were successfully synthesized. Their antifouling activity and toxicity to the cypris larvae of the barnacle Amphibalanus amphitrite and ecotoxicity to the marine crustacean Tigriopus japonicus were studied. It was revealed that the two side chains of omaezallene were essential to its antifouling activity because the activities of nor-bromoallene and nor-bromodiene were significantly diminished. The bromoenyne was found to exhibit potent antifouling activities comparable to omaezallene with low toxicity and ecotoxicity. Preparation of bromoenyne framework is much easier than that of bromodiene moiety in omaezallene. Based on the antifouling activities of the bromoenynes, the synthesis of fluorescent probes and evaluation of their biological activities were also carried out.


Assuntos
Crustáceos/efeitos dos fármacos , Hidrocarbonetos Bromados/síntese química , Thoracica/efeitos dos fármacos , Animais , Cromatografia em Camada Delgada , Crustáceos/genética , Desenho de Drogas , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacologia , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/farmacologia , Larva/efeitos dos fármacos , Análise Espectral/métodos , Relação Estrutura-Atividade , Thoracica/crescimento & desenvolvimento
17.
J Am Chem Soc ; 140(50): 17433-17438, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30516995

RESUMO

A strategy for the installation of small alkyl fragments onto pharmaceutically relevant aliphatic structures has been established via metallaphotoredox catalysis. Herein, we report that tris(trimethylsilyl)silanol can be employed as an effective halogen abstraction reagent that, in combination with photoredox and nickel catalysis, allows a generic approach to Csp3-Csp3 cross-electrophile coupling. In this study, we demonstrate that a variety of aliphatic drug-like groups can be successfully coupled with a number of commercially available small alkyl electrophiles, including methyl tosylate and strained cyclic alkyl bromides. Moreover, the union of two secondary aliphatic carbon centers, a long-standing challenge for organic molecule construction, has been accomplished with a wide array of structural formats. Last, this technology can be selectively merged with Csp2-Csp3 aryl-alkyl couplings to build drug-like systems in a highly modular fashion.


Assuntos
Hidrocarbonetos Bromados/química , Compostos de Trimetilsilil/química , Alcanos/síntese química , Catálise/efeitos da radiação , Complexos de Coordenação/química , Complexos de Coordenação/efeitos da radiação , Irídio/química , Irídio/efeitos da radiação , Luz , Estrutura Molecular , Níquel/química
18.
Comput Biol Chem ; 77: 390-401, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30469054

RESUMO

The B-cell lymphoma-2 (Bcl-2) family proteins have been attributed to be the key regulators in programmed cell death and apoptosis with a prominent role in human cancer. Understanding the fundamental principles of cell survival and death have been the main cornerstone in cancer drug discovery for identification of novel anticancer agents. In this context the Bcl-2 family of anti-and pro-apoptotic proteins provide an excellent opportunity for development of anticancer agents, as blocking the Bcl-2 or Bcl-XL functionally promotes apoptosis in tumor cells and also sensitize them to chemo- and radiotherapies. The present study reports the identification of novel Aplysin analogs as BCL-2 inhibitors from a sequential virtual screening approach using drug-like, ADMET, docking, pharmacophore filters and molecular dynamics simulation. We identified promising Aplysin analogs that have a potential to be Bcl-2 inhibitors just like the standard drug Obatoclax. One of the compound analog 11 was identified to be a promising inhibitor of Bcl-2 in the docking, pharmacophore and simulation based models.The molecular modeling information provided here can be vital in designing of the novel Bcl-2 inhibitors.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Projeto Auxiliado por Computador , Desenho de Drogas , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
19.
Adv Mar Biol ; 81: 167-211, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30471656

RESUMO

Emerging contaminants (ECs) may pose adverse effects on the marine ecosystem and human health. Based on the analysis of publications filed in recent years, this paper provides a comprehensive overview on three prominent groups of ECs, i.e., brominated flame retardants, microplastics, and biocides. It includes detailed discussions on: (1) the occurrence of ECs in seawater, sediment, and biota; (2) analytical detection and monitoring approaches for these target ECs; and (3) the biological impacts of the ECs on humans and other trophic levels. This review provides a summary of recent advances in the field and remaining knowledge gaps to address, to enable the assessment of risk and support the development of regulations and mitigation technologies for the control of ECs in the marine environment.


Assuntos
Desinfetantes/química , Retardadores de Chama/análise , Plásticos/química , Poluentes Químicos da Água/química , Monitoramento Ambiental , Hidrocarbonetos Bromados/química , Oceanos e Mares
20.
Molecules ; 23(12)2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30486415

RESUMO

The dissociative ionization and Coulomb explosion of molecular bromocyclopropane (BCP) has been experimentally investigated by time-of-flight mass spectrum and dc-slice imaging technology. The sliced 2D images, kinetic energy releases and angular distributions of the fragment ions are obtained under the intense femtosecond laser fields (8.0 × 1013⁻2.0 × 1014 W/cm²). The results indicated that the low kinetic energy release (KER) components come from dissociative ionization of BCP⁺, while the high KER components come from Coulomb explosion of BCP2+. The chemical reaction path of BCP⁺ has been calculated by ab initio calculation, furthermore, the C-Br bond cleavage involved Coulomb explosion channels have been revealed, and the corresponding dehydrogenation mechanism has been confirmed.


Assuntos
Ciclopropanos/química , Hidrocarbonetos Bromados/química , Lasers , Espectrometria de Massas
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