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1.
J Oleo Sci ; 69(11): 1437-1443, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33055440

RESUMO

We report the synthesis of bolaamphiphilic alkenyl phosphonic acid (BPC12) through the olefin crossmetathesis reaction of vinylphosphonic acid with 1,11-dodecadiene in the presence of a Ru-carbene catalyst. BPC12 possesses two trans-P-C=C moieties and is thus readily soluble in water up to 3.4 g L-1, as confirmed by 1H nuclear magnetic resonance (NMR) measurements. Surface tension measurements revealed that BPC12 reduced the surface tension of water from 72.0 to 47.0 mN m‒1. The occupied area per molecule at the air/water interface (A) of BPC12 (216 Å2) was ten times larger than that of dodecenyl phosphonic acid PC12 (23 Å2). Moreover, dynamic light scattering measurement of an aqueous BPC12 solution (5 mM) revealed the formation of large aggregates with an average diameter of 81.8±27.0 nm.


Assuntos
Alcenos/química , Metano/análogos & derivados , Organofosfonatos/química , Ácidos Fosforosos/síntese química , Compostos de Vinila/química , Ar , Catálise , Difusão Dinâmica da Luz , Espectroscopia de Ressonância Magnética , Metano/química , Fenômenos de Química Orgânica , Tamanho da Partícula , Ácidos Fosforosos/química , Solubilidade , Tensão Superficial , Água
2.
PLoS One ; 15(9): e0238470, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32911526

RESUMO

We report a powerful method for capturing the time-resolved concentration profiles, liquid swelling and surface phenomena during the absorption of methane (CH4) in still liquid ethanol (C2D6O) and n-decane (n-C10D22) and at high spatial resolution (pixel size 21.07 µm) using neutron imaging. Absorption of supercritical methane was followed at two temperatures and two pressures of methane, namely 7.0, 37.8 °C and 80, 120 bar. Fick's second law, which was used in the liquid-fixed coordinates, enabled for an adequate parameterization of the observed concentration profiles and liquid levels using simple analytical expressions. For both studied liquids, anomalously slow diffusion was observed in the initial stage of the absorption experiment. This was ascribed to the slow formation of the surface excess on the interface, time constant ranged 130-275 s. The axial symmetry of the cell allowed for the tomographic reconstructions of the profiles of the menisci. Based on these profiles, contact angle and surface tension were evaluated using the Young-Laplace equation. Overall, neutron imaging made it possible to capture time- and space-resolved information from which the methane concentration, liquid level and meniscus shape under high-pressure conditions inside a cylindrical titanium vessel were quantitatively derived. Multiple characteristics of ethanol, a methane hydrate inhibitor, and n-decane, a model constituent of crude oil, were thus measured for the first time under industrially relevant conditions in a one-pot experiment.


Assuntos
Metano/química , Imagem Individual de Molécula/métodos , Alcanos/química , Difusão , Etanol/química , Modelos Estatísticos , Nêutrons , Petróleo , Fenômenos Físicos , Imagem Individual de Molécula/instrumentação , Temperatura , Água
3.
Sci Rep ; 10(1): 14937, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913281

RESUMO

Silver nanoparticles (Ag NPs) system capable of exhibiting different particle size at different temperature was developed, which depended on the extent of Diels-Alder (DA) reaction of bismaleimide with furan. Thus, Ag NPs were functionalized on the surface by a furyl-substituted carbene through an insertion reaction. Subsequent reversible DA crosslinking achieved a controlled aggregation with different particle size, which gives a series of different antibacterial activity. These Ag NPs were characterized by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), X-ray Photoelectron Spectroscopy (XPS), and Nanoparticle Size Analyzer. The aggregation of the Ag NPs could be reliably adjusted by varying the temperature of DA/reverse-DA reaction. The antibacterial activity was assessed using the inhibition zone method against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), which decreased first and then increased in agreement with the size evolution of Ag NPs. This approach opens a new horizon for the carbene chemistry to modify silver nanoparticles with variable size and give controlled antibacterial activity.


Assuntos
Antibacterianos/administração & dosagem , Escherichia coli/crescimento & desenvolvimento , Nanopartículas Metálicas/administração & dosagem , Metano/análogos & derivados , Prata/química , Staphylococcus aureus/crescimento & desenvolvimento , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Nanopartículas Metálicas/química , Metano/química , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Staphylococcus aureus/efeitos dos fármacos
4.
Nat Commun ; 11(1): 3880, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32759942

RESUMO

Geological sources of H2 and abiotic CH4 have had a critical role in the evolution of our planet and the development of life and sustainability of the deep subsurface biosphere. Yet the origins of these sources are largely unconstrained. Hydration of mantle rocks, or serpentinization, is widely recognized to produce H2 and favour the abiotic genesis of CH4 in shallow settings. However, deeper sources of H2 and abiotic CH4 are missing from current models, which mainly invoke more oxidized fluids at convergent margins. Here we combine data from exhumed subduction zone high-pressure rocks and thermodynamic modelling to show that deep serpentinization (40-80 km) generates significant amounts of H2 and abiotic CH4, as well as H2S and NH3. Our results suggest that subduction, worldwide, hosts large sources of deep H2 and abiotic CH4, potentially providing energy to the overlying subsurface biosphere in the forearc regions of convergent margins.


Assuntos
Ecossistema , Hidrogênio/química , Metano/química , Minerais/química , Compostos Orgânicos/química , Termodinâmica , Amônia/química , Fenômenos Químicos , Fenômenos Geológicos , Sulfeto de Hidrogênio/química , Fenômenos Mecânicos , Fenômenos de Química Orgânica , Alcaloides de Triptamina e Secologanina/química , Erupções Vulcânicas
5.
J Oleo Sci ; 69(8): 871-882, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32641614

RESUMO

In this study, an N-heterocyclic carbene (NHC)-based metal coordinate surfactant (MCS), NHC-Au-MCS, in which the NHC framework afforded the bonding of the Au(I) at the linkage of the hydrophilic and hydrophobic moieties, was synthesized. The structure of NHC-Au-MCS was confirmed by 1H and 13C NMR spectroscopic measurements together with elemental analysis. Matrix-assisted laser desorption/ionization (MALDI), laser desorption/ionization (LDI), and electrospray ionization mass spectrometry (ESI-MS) indicated the distinct reactivity of NHC-Au-MCS, such as the exchange of Br to Cl and the formation of a cationic Au complex, where the two NHC ligands were coordinated to an Au(I) center upon laser activation. The surface tension and dynamic light scattering (DLS) measurements revealed that the coordination of Au(I) to NHC reduced the critical micelle concentration (CMC) of NHC-Au-MCS (1.3×10-5 M), which resulted in the formation of micelles at concentrations higher than the CMC in water. We also confirmed that the surface-active Au(I) complex of NHC-Au-MCS catalyzed the hydration of 1-dodecyne to 2-dodecanone in water in the absence of an organic solvent. On the basis of the detailed mechanistic investigations regarding the reactivity of NHC-Au-MCS, we revealed that NHC-Au-MCS partially translated into Au nanoparticles (AuNPs), which facilitated alkyne hydration. These mechanistic studies were supported by UV-vis measurements, transmission electron microscopy (TEM), and LDI-MS.


Assuntos
Alquinos/química , Ouro/química , Compostos Heterocíclicos/síntese química , Nanopartículas Metálicas/química , Metano/análogos & derivados , Tensoativos/síntese química , Catálise , Compostos Heterocíclicos/química , Hidrogenação , Interações Hidrofóbicas e Hidrofílicas , Metano/síntese química , Metano/química , Micelas , Tensoativos/química , Água
6.
Top Curr Chem (Cham) ; 378(3): 39, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32367181

RESUMO

During the last decade, organometallic, coordination, and catalytic chemistry of the three-dimensional metals such as copper (Cu) has been greatly affected by the emergence of nitrogen heterocyclic carbene (NHC) complexes. The NHCs, and in particular the mononuclear CuI-based ones, have been proven vastly useful in several applications such as in biosynthesis, catalysis, photochemistry, etc. This review tries to thoroughly describe a series of mononuclear CuI NHC complexes and their subcategories such as heteroleptics, and bidentate and tridentate heteroatom complexes, and give some detailed insights on their development, emergence, and applications. A brief outlook is also disclosed to enable other researchers to further develop a platform for future advances and studies in the field of CuI-based NHCs.


Assuntos
Complexos de Coordenação/química , Cobre/química , Compostos Heterocíclicos/química , Metano/análogos & derivados , Nitrogênio/química , Complexos de Coordenação/síntese química , Metano/química , Estrutura Molecular
7.
Chem Commun (Camb) ; 56(43): 5718-5734, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32391543

RESUMO

Strain-release driven transformations give access to attractive bioisosteric motifs highly prized by medicinal chemists and they are characteristic of molecules possessing distorted bond lengths and angles. By broadening the chemical space in drug discovery, recently, these compounds have attracted a lot of interest. Their reactivity stems mainly from an increased energy and destabilization. As a result, the opening of the bridging bond occurs under the action of both nucleophiles and electrophiles as well as radical species and transition metals. Though the bridge bond dominates their reactivity, it is also influenced by the substitution pattern. This feature article focuses on strain-release driven strategies paying particular attention to the most recent (year > 2010) advances.


Assuntos
Técnicas de Química Sintética , Catálise , Reação de Cicloadição , Metano/análogos & derivados , Metano/química , Compostos Organometálicos/química , Elementos de Transição/química
8.
Chimia (Aarau) ; 74(4): 278-284, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32331547

RESUMO

N-Heterocyclic carbenes (NHCs) are the ligands of choice in a large variety of transformations entailing different transition metals. However, the number and variety of chiral NHCs suitable as stereo-controlling ligands in asymmetric catalysis remains limited. Herein we highlight the introduction of a modular NHC ligand family, consisting of a chiral version of the widely used IPr ligand. These chiral NHC ligands were applied in the nickel-catalyzed enantioselective C-H functionalization of N-heterocycles. Nickel-NHC catalysis unlocked the stereoselective C-H annulation of 2- and 4-pyridones, delivering fused bicyclic compounds found in many biologically active compounds. Applying a bulky, yet flexible ligand scaffold enabled the highly enantioselective C-H functionalization of pyridones under mild conditions. The introduction of a bulky chiral SIPr analogue enabled the nickel-catalyzed enantioselective C-H functionalization of indoles, yielding valuable tetrahydropyridoindoles. Additionally, pyrrolopyridines, pyrrolopyrimidines and pyrroles were efficiently functionalized, delivering chiral annulated azoles.


Assuntos
Metano/análogos & derivados , Catálise , Compostos Heterocíclicos , Ligantes , Metano/química , Níquel , Estereoisomerismo
9.
Sci Rep ; 10(1): 4682, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170164

RESUMO

Benthic microorganisms transported into the water column potentially influence biogeochemical cycles and the pelagic food web structure. In the present study six gas-releasing vent sites in the Coal Oil Point seep field (California) were investigated, and the dislocation of microorganisms from the sediment into the water column via gas bubbles released from the seabed was documented. It was found that the methanotrophs transport efficiency was dependent on the volumetric gas flow, with the highest transport rate of 22.7 × 103 cells mLgas-1 at a volumetric gas flow of 0.07 mLgas s-1, and the lowest rate of 0.2 × 103 cells mLgas-1 at a gas flow of 2.2 mLgas s-1. A simple budget approach showed that this bubble-mediated transport has the potential to maintain a relevant part of the water-column methanotrophs in the seep field. The bubble-mediated link between the benthic and pelagic environment was further supported by genetic analyses, indicating a transportation of methanotrophs of the family Methylomonaceae and oil degrading bacteria of the genus Cycloclasticus from the sediment into the water column. These findings demonstrate that the bubble-mediated transport of microorganisms influences the pelagic microbial abundance and community composition at gas-releasing seep sites.


Assuntos
Sedimentos Geológicos/microbiologia , Metano , Microbiota , Microbiologia da Água , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Água Subterrânea/análise , Água Subterrânea/química , Água Subterrânea/microbiologia , Metano/química , Metano/metabolismo
10.
Science ; 367(6482): 1091-1097, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32139536

RESUMO

Many disease pathologies can be understood through the elucidation of localized biomolecular networks, or microenvironments. To this end, enzymatic proximity labeling platforms are broadly applied for mapping the wider spatial relationships in subcellular architectures. However, technologies that can map microenvironments with higher precision have long been sought. Here, we describe a microenvironment-mapping platform that exploits photocatalytic carbene generation to selectively identify protein-protein interactions on cell membranes, an approach we term MicroMap (µMap). By using a photocatalyst-antibody conjugate to spatially localize carbene generation, we demonstrate selective labeling of antibody binding targets and their microenvironment protein neighbors. This technique identified the constituent proteins of the programmed-death ligand 1 (PD-L1) microenvironment in live lymphocytes and selectively labeled within an immunosynaptic junction.


Assuntos
Antígeno B7-H1/metabolismo , Membrana Celular/metabolismo , Microambiente Celular , Linfócitos/metabolismo , Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas , Catálise , Membrana Celular/efeitos da radiação , Transferência de Energia , Humanos , Células Jurkat , Linfócitos/efeitos da radiação , Metano/análogos & derivados , Metano/química , Metano/efeitos da radiação , Processos Fotoquímicos , Raios Ultravioleta
11.
Mikrochim Acta ; 187(4): 233, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32180017

RESUMO

Two-dimensional (2D) COFs have been successfully applied for various applications, such as capillary electrochromatography (CEC). Compared with 2D COFs, three-dimensional (3D) COFs have higher surface area and lower density, which should have superior potential as the separation medium in CEC. However, the 3D COFs on the inner wall of capillary is hard to fabricate in situ. Up to date, the application of 3D COFs in open-tubular capillary electrochromatography (OT-CEC) is still considered a challenge. For the first time the COF-300-coated capillary was prepared by in situ growth (COF-300 was made from terephthalaldehyde and tetra-(4-anilyl)-methane) on OT-CEC. Benzene, methylbenzene, styrene, ethylbenzene, naphthalene, 1-methylnaphthalene, and propylbenzene were used to evaluate the performance of the COF-300-coated capillary by OT-CEC. For three consecutive runs, the intraday relative standard deviations (RSDs) of migration time and peak areas were 0.1-0.4% and 2.5-8.3%, respectively. The interday RSDs of migration time and peak areas were 0.2-0.5% and 1.0-10.8%, respectively. Five groups of aromatic co mpounds were used to further study the separation mechanism, which indicated that hydrophobic interaction and size selection interaction are the main factors. It should be noted that the COF-300-coated capillary can be used for more than 140 runs with no observable changes of the separation efficiency. Graphical abstract The 3D COF-300-coated capillary was prepared by in situ growth for OT-CEC. Six groups of aromatic compounds were separated by 3D COF-300-coated capillary. Size selection and hydrophobic interaction affect the migration time of analytes.


Assuntos
Aldeídos/química , Hidrocarbonetos Aromáticos/isolamento & purificação , Metano/química , Eletrocromatografia Capilar , Hidrocarbonetos Aromáticos/química , Metano/análogos & derivados
12.
Arch Pharm (Weinheim) ; 353(5): e1900333, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32115728

RESUMO

In continuation of our previous work on anticancer and anti-inflammatory agents, a series of 22 novel methylene-bearing sulfur-containing cyanopyrimidine derivatives was synthesized by Biginelli condensation reaction, which was followed by nucleophilic substitution of the chloro group with secondary or tertiary amines. Structural confirmation of these derivatives was attained through different spectral techniques. Then, anticancer evaluation of these compounds was done at the National Cancer Institute. Compounds 4g, 4j, 4k, and 4v demonstrated appreciable results against different cell lines. Among the synthesized compounds, 4g (NSC: 795475) exhibited a growth inhibition (GI) of 81.34% against the NCI-H460 lung cancer cell line, 72.64% against the ACHN renal cancer cell line, and 112.17% against the OVCAR-4 ovarian cancer cell line. Compound 4j (NSC: 795746) was active against U-251 CNS cancer, OVCAR-4 ovarian cancer, and 786-0 and ACHN renal cancer cell lines, with GI of 78.84%, 150.38%, 75.64%, and 86.45%, respectively. The literature supporting the association between cancer and underlying inflammation prompted us to evaluate the four compounds, 4g, 4j, 4k, and 4v, with appreciable anticancer activity for their in vitro anti-inflammatory activity. Cyclooxygenase (COX)-2 inhibition studies were also performed to study the molecular target. To validate the target study, molecular docking studies in the ligand-binding domain of COX-2 (PDB ID: 1CX2) were also performed. Compounds 4g, 4j, and 4k did not show cytotoxicity on RAW 264.7 cells up to 10 µM concentration; however, compound 4v showed cytotoxic effects at 10 µM concentration.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Metano/farmacologia , Pirimidinas/farmacologia , Enxofre/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Metano/química , Camundongos , Modelos Moleculares , Estrutura Molecular , Pirimidinas/química , Células RAW 264.7 , Relação Estrutura-Atividade , Enxofre/química
13.
Dalton Trans ; 49(8): 2505-2516, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32022055

RESUMO

In this study, we designed and synthesized four novel multi-nuclear silver complexes (1-4) coordinated with pyrazole- or pyridine-functionalized N-heterocyclic carbene (NHC) ligands. The crystal structures of the silver-NHC complexes were confirmed by X-ray diffraction analysis. In vitro assays showed that the silver-NHC complexes effectively killed a broad range of cancer cells after short-term drug exposure, serving as fast-acting cytotoxic agents. Of note, in cisplatin-resistant A549 cancer cells, the silver complexes were not cross-resistant with the clinically used cisplatin agent. Detailed mechanistic studies revealed that complex 2 triggered caspase-independent cell necrosis associated with intracellular reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) depletion. By exploiting a facile nano-assembly process, silver-NHC complexes 1, 2 and 4 were successfully integrated into the hydrophobic cores of amphiphilic matrices (DSPE-PEG2K), enabling systemic injection. The silver complex-loaded nanotherapeutics (1-NPs, 2-NPs, and 4-NPs) showed high safety margins with reduced systemic drug toxicities relative to cisplatin in animals. Furthermore, in a xenograft model of human colorectal cancer, the administration of the nanotherapeutics resulted in a marked inhibition of tumor progression.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Metano/análogos & derivados , Nanopartículas/química , Pirazóis/química , Piridinas/química , Prata/química , Células A549 , Animais , Apoptose , Proliferação de Células , Neoplasias do Colo/patologia , Compostos Heterocíclicos/farmacologia , Humanos , Metano/química , Camundongos , Estrutura Molecular , Nanopartículas/administração & dosagem , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Sci Total Environ ; 713: 136739, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32019052

RESUMO

Nitrate-dependent anaerobic methane oxidation (N-DAMO), a bioprocess that couples the oxidation of green gas and the removal of nitrogen oxides in a microbial group, has gained much attention as a potential economical method of biological removal of nitrates and methane from wastewater. Low-temperature (20 °C) operation of N-DAMO would be beneficial to utilize the methane dissolved in the effluent and thus decrease the cost of maintaining the bioreactor temperature in wastewater treatment. Here, the long-term (>350 days) operational activities of N-DAMO were evaluated to assess the performance of N-DAMO from stepwise cooling (30-20 °C) to ambient temperatures (13-38 °C). Under stepwise cooling conditions, the activity of the N-DAMO community was first inhibited and then rapidly adjusted. Notably, a similar N-DAMO activity was observed at 30 °C and 20 °C. Under ambient temperature conditions, the highest nitrate removal rate observed at the beginning of the test was 7.14 mg-N/L/d, which was 5.3 times higher than that recorded at the end of the test. This indicates that the long-term temperature fluctuation irreversibly inhibited N-DAMO activity. 16S rRNA gene sequencing analyses found that the functional archaea were ANME-2D, which has been deemed as the dominant culture in the N-DAMO process. The abundance of ANME-2D on the last day at stepwise cooling temperature conditions was much higher than on day 0, but disappeared after a long period of operation at ambient temperature. It was assumed that N-DAMO would stabilize at stepwise cooling temperature conditions, but not at ambient temperature. Our findings could offer a promising technology for anaerobic wastewater treatment plants (WWTPs) in temperate and warm climate zones.


Assuntos
Metano/química , Anaerobiose , Reatores Biológicos , Desnitrificação , Nitritos , Oxirredução , RNA Ribossômico 16S , Temperatura
15.
Molecules ; 25(4)2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32059503

RESUMO

Cyclic amino(ylide)carbenes (CAYCs) are the ylide-substituted analogues of N-heterocyclic Carbenes (NHCs). Due to the stronger π donation of the ylide compared to an amino moiety they are stronger donors and thus are desirable ligands for catalysis. However, no stable CAYC has been reported until today. Here, we describe experimental and computational studies on the synthesis and stability of CAYCs based on pyrroles with trialkyl onium groups. Attempts to isolate two CAYCs with trialkyl phosphonium and sulfonium ylides resulted in the deprotonation of the alkyl groups instead of the formation of the desired CAYCs. In case of the PCy3-substituted system, the corresponding ylide was isolated, while deprotonation of the SMe2-functionalized compound led to the formation of ethene and the thioether. Detailed computational studies on various trialkyl onium groups showed that both the α- and ß-deprotonated compounds were energetically favored over the free carbene. The most stable candidates were revealed to be α-hydrogen-free adamantyl-substituted onium groups, for which ß-deprotonation is less favorable at the bridgehead position. Overall, the calculations showed that the isolation of CAYCs should be possible, but careful design is required to exclude decomposition pathways such as deprotonations at the onium group.


Assuntos
Hidrogênio/química , Metano/análogos & derivados , Estrutura Molecular , Catálise , Metano/síntese química , Metano/química , Estereoisomerismo , Sulfetos/química
16.
Inorg Chem ; 59(5): 3312-3320, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32049516

RESUMO

We carried out a detailed theoretical study on the mechanism of the carbene ligand substitution by cysteine and selenocysteine residues in an Au(I) bis-N-heterocyclic carbene complex in order to model the initial stages of the mechanism of action of this promising class of antitumor metallodrug. Both neutral and deprotonated capped Cys and Sec species were considered as possible nucleophiles in the ligand exchange reaction on the metal center to model the corresponding protein side chains. Energies and geometric structures of the possible transition states and reactant- and product-adducts involved in the substitution process have been calculated using density functional theory and local MP2. Reaction and activation enthalpies and free energies have been evaluated and indicate a slightly exothermic and exergonic process with reasonably low barriers, 21.3 and 19.6 kcal mol-1, respectively, for capped Cys and Sec, in good agreement with the experimental data available for the reaction with free amino acids. The results suggest a mechanism for the ligand exchange reaction involving an anionic thiolate or selenothiolate species coupled to an explicit proton transfer to the leaving carbene from the acidic component of the buffer. The presence of a buffer is necessary both in in vitro experiments and under physiological conditions, and its proton reservoir behavior reveals the importance of the environmental effects in carbene substitution by biological nucleophiles.


Assuntos
Antineoplásicos/química , Cisteína/química , Ouro/química , Compostos Heterocíclicos/química , Metano/análogos & derivados , Antineoplásicos/síntese química , Cisteína/análogos & derivados , Teoria da Densidade Funcional , Metano/química , Estrutura Molecular
17.
Inorg Chem ; 59(5): 3281-3289, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32073260

RESUMO

Metal complexes provide a versatile platform to develop novel anticancer pharmacophores, and they form stable compounds with N-heterocyclic carbene (NHC) ligands, some of which have been shown to inhibit the cancer-related selenoenzyme thioredoxin reductase (TrxR). To expand a library of isostructural NHC complexes, we report here the preparation of RhIII- and IrIII(Cp*)(NHC)Cl2 (Cp* = η5-pentamethylcyclopentadienyl) compounds and comparison of their properties to the RuII- and OsII(cym) analogues (cym = η6-p-cymene). Like the RuII- and OsII(cym) complexes, the RhIII- and IrIII(Cp*) derivatives exhibit cytotoxic activity with half maximal inhibitory concentration (IC50) values in the low micromolar range against a set of four human cancer cell lines. In studies on the uptake and localization of the compounds in cancer cells by X-ray fluorescence microscopy, the Ru and Os derivatives were shown to accumulate in the cytoplasmic region of treated cells. In an attempt to tie the localization of the compounds to the inhibition of the tentative target TrxR, it was surprisingly found that only the Rh complexes showed significant inhibitory activity at IC50 values of ∼1 µM, independent of the substituents on the NHC ligand. This indicates that, although TrxR may be a potential target for anticancer metal complexes, it is unlikely the main target or the sole target for the Ru, Os, and Ir compounds described here, and other targets should be considered. In contrast, Rh(Cp*)(NHC)Cl2 complexes may be a scaffold for the development of TrxR inhibitors.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Inibidores Enzimáticos/farmacologia , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Humanos , Ligantes , Metais Pesados/química , Metais Pesados/farmacologia , Metano/análogos & derivados , Metano/química , Metano/farmacologia , Conformação Molecular , Relação Estrutura-Atividade , Tiorredoxina Dissulfeto Redutase/metabolismo
18.
Environ Microbiol ; 22(4): 1222-1237, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017377

RESUMO

Extraction of natural gas from unconventional hydrocarbon reservoirs by hydraulic fracturing raises concerns about methane migration into groundwater. Microbial methane oxidation can be a significant methane sink. Here, we inoculated replicated, sand-packed, continuous mesocosms with groundwater from a field methane release experiment. The mesocosms experienced thirty-five weeks of dynamic methane, oxygen and nitrate concentrations. We determined concentrations and stable isotope signatures of methane, carbon dioxide and nitrate and monitored microbial community composition of suspended and attached biomass. Methane oxidation was strictly dependent on oxygen availability and led to enrichment of 13 C in residual methane. Nitrate did not enhance methane oxidation under oxygen limitation. Methylotrophs persisted for weeks in the absence of methane, making them a powerful marker for active as well as past methane leaks. Thirty-nine distinct populations of methylotrophic bacteria were observed. Methylotrophs mainly occurred attached to sediment particles. Abundances of methanotrophs and other methylotrophs were roughly similar across all samples, pointing at transfer of metabolites from the former to the latter. Two populations of Gracilibacteria (Candidate Phyla Radiation) displayed successive blooms, potentially triggered by a period of methane famine. This study will guide interpretation of future field studies and provides increased understanding of methylotroph ecophysiology.


Assuntos
Bactérias/metabolismo , Água Subterrânea/química , Metano/química , Microbiologia da Água , Gás Natural , Nitratos/metabolismo , Oxirredução
19.
Molecules ; 25(4)2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32079259

RESUMO

The direct C-H functionalization reaction is one of the most efficient strategies by which to introduce new functional groups into small organic molecules. Over time, iron complexes have emerged as versatile catalysts for carbine-transfer reactions with diazoalkanes under mild and sustainable reaction conditions. In this review, we discuss the advances that have been made using iron catalysts to perform C-H functionalization reactions with diazoalkanes. We give an overview of early examples employing stoichiometric iron carbene complexes and continue with recent advances in the C-H functionalization of C(sp2)-H and C(sp3)-H bonds, concluding with the latest developments in enzymatic C-H functionalization reactions using iron-heme-containing enzymes.


Assuntos
Ferro/química , Metano/análogos & derivados , Biocatálise , Ciclização , Ésteres/química , Ligação de Hidrogênio , Metano/química , Estereoisomerismo
20.
Nature ; 578(7795): 409-412, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32076219

RESUMO

Atmospheric methane (CH4) is a potent greenhouse gas, and its mole fraction has more than doubled since the preindustrial era1. Fossil fuel extraction and use are among the largest anthropogenic sources of CH4 emissions, but the precise magnitude of these contributions is a subject of debate2,3. Carbon-14 in CH4 (14CH4) can be used to distinguish between fossil (14C-free) CH4 emissions and contemporaneous biogenic sources; however, poorly constrained direct 14CH4 emissions from nuclear reactors have complicated this approach since the middle of the 20th century4,5. Moreover, the partitioning of total fossil CH4 emissions (presently 172 to 195 teragrams CH4 per year)2,3 between anthropogenic and natural geological sources (such as seeps and mud volcanoes) is under debate; emission inventories suggest that the latter account for about 40 to 60 teragrams CH4 per year6,7. Geological emissions were less than 15.4 teragrams CH4 per year at the end of the Pleistocene, about 11,600 years ago8, but that period is an imperfect analogue for present-day emissions owing to the large terrestrial ice sheet cover, lower sea level and extensive permafrost. Here we use preindustrial-era ice core 14CH4 measurements to show that natural geological CH4 emissions to the atmosphere were about 1.6 teragrams CH4 per year, with a maximum of 5.4 teragrams CH4 per year (95 per cent confidence limit)-an order of magnitude lower than the currently used estimates. This result indicates that anthropogenic fossil CH4 emissions are underestimated by about 38 to 58 teragrams CH4 per year, or about 25 to 40 per cent of recent estimates. Our record highlights the human impact on the atmosphere and climate, provides a firm target for inventories of the global CH4 budget, and will help to inform strategies for targeted emission reductions9,10.


Assuntos
Atmosfera/química , Combustíveis Fósseis/história , Combustíveis Fósseis/provisão & distribução , Atividades Humanas/história , Metano/análise , Metano/história , Biomassa , Radioisótopos de Carbono , Carvão Mineral/história , Carvão Mineral/provisão & distribução , Aquecimento Global/prevenção & controle , Aquecimento Global/estatística & dados numéricos , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Camada de Gelo/química , Metano/química , Gás Natural/história , Gás Natural/provisão & distribução , Petróleo/história , Petróleo/provisão & distribução
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