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1.
PLoS One ; 15(9): e0238140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881943

RESUMO

Vitamin E acetate (VEA) is strongly linked to the outbreak of electronic-cigarette or vaping product use-associated lung injury (EVALI). It has been proposed that VEA decomposition to ketene-a respiratory poison that damages lungs at low ppm levels-may play a role in EVALI. However, there is no information available on the temperature at which VEA decomposes and how this correlates with the vaping process. We have studied the temperature-dependent kinetics of VEA decomposition using quantum chemical and statistical mechanical modelling techniques, developing a chemical kinetic model of the vaping process. This model predicts that, under typical vaping conditions, the use of VEA contaminated e-cigarette products is unlikely to produce ketene at harmful levels. However, at the high temperatures encountered at low e-cigarette product levels, which produce 'dry hits', ketene concentrations are predicted to reach acutely toxic levels in the lungs (as high as 30 ppm). We therefore hypothesize that dry hit vaping of e-cigarette products containing VEA contributes to EVALI.


Assuntos
Etilenos/metabolismo , Cetonas/metabolismo , Lesão Pulmonar/patologia , Vaping/efeitos adversos , Vitamina E/metabolismo , Etilenos/química , Etilenos/toxicidade , Humanos , Cetonas/química , Cetonas/toxicidade , Cinética , Lesão Pulmonar/induzido quimicamente , Temperatura , Vitamina E/química
2.
Int J Nanomedicine ; 15: 5017-5026, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764933

RESUMO

Background: Molecular imaging is of great benefit to early disease diagnosis and timely treatment. One of the most striking innovations is the development of multimodal molecular imaging technology, which integrates two or more imaging modalities, largely in view of making the best of the advantages of each modality while overcoming their respective shortcomings. Hence, engineering a versatile and easily prepared nanomaterial with integrating multimodal molecular imaging function holds great promise, but is still a great challenge. Materials and Methods: We firstly designed and synthesized a BDT-DPP conjugated polymer and then noncovalent self-assembly with phospholipid-polyethylene glycol endowed BDT-DPP with water solubility and biocompatibility. Followed by [Cu] labeling, the acquired multifunctional nanoparticles (NPs) were studied in detail for the photophysical property. The cytotoxicity and biocompatibility of DPP-BDT NPs were examined through MTT assay and H&E stained analysis. In addition, we investigated the accumulation of the NPs in HepG2 tumor models by positron emission tomography (PET) and photoacoustic (PA) dual-mode imaging. Results and Discussion: The DPP-BDT NPs exhibited excellent optical stability, strong near-infrared (NIR) light absorption as well as fine biocompatibility. After tail vein injection into the living mice, the PA signals in the neoplastic tissues were gradually increased and reached to the maximum at the 4-h post-injection, which was consistent with the PET analysis. Such strong PA and PET signals were attributed to the efficient NPs accumulation resulting from the enhanced permeability and retention (EPR) effect. Conclusion: The biocompatible DPP-BDT NPs demonstrated to be strong NIR absorption property and PAI sensitivity. Besides, these novel DPP-BDT NPs can act not only as a PA imaging contrast agent but also as an imaging agent for PET.


Assuntos
Cetonas/química , Nanopartículas/química , Neoplasias Experimentais/diagnóstico por imagem , Técnicas Fotoacústicas/métodos , Tomografia por Emissão de Pósitrons/métodos , Pirróis/química , Animais , Meios de Contraste/química , Radioisótopos de Cobre/administração & dosagem , Radioisótopos de Cobre/farmacocinética , Feminino , Células Hep G2 , Humanos , Injeções , Camundongos , Camundongos Nus , Imagem Multimodal/métodos , Células NIH 3T3 , Nanopartículas/administração & dosagem , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Polímeros/química , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/química , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Nat Commun ; 11(1): 3538, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669587

RESUMO

Ever since Hirata's report of yuzurimine in 1966, nearly fifty yuzurimine-type alkaloids have been isolated, which formed the largest subfamily of the Daphniphyllum alkaloids. Despite extensive synthetic studies towards this synthetically challenging and biologically intriguing family, no total synthesis of any yuzurimine-type alkaloids has been achieved to date. Here, the first enantioselective total synthesis of (+)-caldaphnidine J, a highly complex yuzurimine-type Daphniphyllum alkaloid, is described. Key transformations of this approach include a highly regioselective Pd-catalyzed hydroformylation, a samarium(II)-mediated pinacol coupling, and a one-pot Swern oxidation/ketene dithioacetal Prins reaction. Our approach paves the way for the synthesis of other yuzurimine-type alkaloids and related natural products.


Assuntos
Alcaloides/síntese química , Daphniphyllum/química , Produtos Biológicos , Catálise , Desenho de Fármacos , Etilenos/química , Cetonas/química , Espectroscopia de Ressonância Magnética , Modelos Químicos , Estrutura Molecular , Oxirredução , Oxigênio/química , Samário/química , Estereoisomerismo
4.
J Phys Chem Lett ; 11(15): 6262-6265, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32658489

RESUMO

The question of whether COVID protease (SARS-CoV-2 Mpro) can be blocked by inhibitors has been examined, with a particularly successful performance exhibited by α-ketoamide derivative substrates like 13b of Hilgenfeld and co-workers (Zhang, L., et al. Science 2020, 368, 409-412). After the biological characterization, here density functional theory calculations explain not only how inhibitor 13b produces a thermodynamically favorable interaction but also how to reach it kinetically. The controversial and unprovable concept of aromaticity here enjoys being the agent that rationalizes the seemingly innocent role of histidine (His41 of Mpro). It has a hydrogen bond with the hydroxyl group and is the proton carrier of the thiol of Cys145 at almost zero energy cost that favors the interaction with the inhibitor that acts as a Michael acceptor.


Assuntos
Antivirais/metabolismo , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Inibidores de Cisteína Proteinase/metabolismo , Histidina/química , Pneumonia Viral/tratamento farmacológico , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/química , Betacoronavirus/enzimologia , Sítios de Ligação , Cisteína Endopeptidases/química , Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/química , Teoria da Densidade Funcional , Ligação de Hidrogênio , Cetonas/química , Cetonas/metabolismo , Modelos Químicos , Pandemias , Ligação Proteica , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo
5.
Chemosphere ; 260: 127593, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32679377

RESUMO

In this study we demonstrate Sulphonated Polyhedral oligomeric silsesquioxane (S-POSS) incorporated Sulphonated Poly Ether Ether Ketone (SPEEK) as an effective cation exchange membrane (CEM) for improving performance and sustainability in a fabricated tubular Microbial Fuel Cell (MFC). The organic-inorganic caged frame of S-POSS enables several ion conducting channels thereby resulting in better proton conductivity and water uptake in addition to hydroxide ions native in POSS. Among the membranes, SPEEK+ 5 wt% S-POSS exhibits a highest maximum performance of 162 ± 1.4 mW m-2 with the highest IEC of 1.8 ± 0.05 meq g-1. Microbial community analysis reveals the predominance of several bacterial strains contributing to wide range of mechanisms. Three phyla including Betaproteobacteria, Gammaproteobacteria and Firmicutes showed maximum predominance. In addition to a novel nanocomposite membrane, the present research introduces perceptions of two metabolic mechanisms of the microbial community available which opens pathway for future insights on how other miniatures involve in electron transfer mechanisms.


Assuntos
Fontes de Energia Bioelétrica/microbiologia , Cetonas/química , Membranas Artificiais , Nanocompostos/química , Compostos de Organossilício/química , Polietilenoglicóis/química , Ácidos Sulfônicos/química , Condutividade Elétrica
6.
Int J Nanomedicine ; 15: 2403-2417, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308391

RESUMO

Purpose: To improve the surface bio-properties of polyetheretherketone (PEEK)/nano magnesium silicate (n-MS) composite (PC). Materials and Methods: The surface of PC was firstly treated by particle impact (PCP) and subsequently modified by concentrated sulfuric acid (PCPS). Results: PCPS surface exhibited not only macropores with sizes of about 150 µm (fabricated by particle impact) but also micropores with sizes of about 2 µm (created by sulfonation of PEEK) on the macroporous walls, and sulfonic acid (-SO3H) groups were introduced on PCPS surface. In addition, many n-MS nanoparticles were exposed on the microporous walls, which formed micro-nano structures. Moreover, the surface roughness and hydrophilicity of PCPS were obviously enhanced as compared with PC and PCP. Moreover, the apatite mineralization of PCPS in simulated body fluid (SBF) was obviously improved as compared with PC. Furthermore, compared with PC and PCP, PCPS exhibited antibacterial performances due to the presence of -SO3H groups. In addition, the responses (eg, adhesion and proliferation as well as differentiation) of bone marrow mesenchymal stem cell of rat to PCPS were significantly promoted as compared with PC and PCP. Conclusion: PCPS with macro-microporous surface containing -SO3H groups and micro-nano structures exhibited antibacterial activity and induced cell responses, which might possess large potential for bone substitute and repair.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Cetonas/química , Silicatos de Magnésio/química , Nanopartículas/química , Polietilenoglicóis/química , Animais , Apatitas/química , Líquidos Corporais/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Interações Hidrofóbicas e Hidrofílicas , Células-Tronco Mesenquimais/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ratos , Ácidos Sulfônicos/química , Propriedades de Superfície
7.
Medicine (Baltimore) ; 99(17): e18594, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332592

RESUMO

Despite the plethora of evidence in support of the use of structural osseous autograft in lumbar spondylodiscitis, attention has recently been turned to the addition of synthetic materials such as polyetheretherketone (PEEK) to restore anterior vertebral column support.From January 2015 to April 2017, 7 patients with lumbar polymicrobial spondylodiscitis were surgically treated with a minimally invasive oblique retroperitoneal approach to the infected focus. The patients underwent a standard lateral minimally invasive oblique retroperitoneal approach using direct lateral interbody fusion system. The PEEK cages were loaded with autologous bone graft. All the patients underwent posterior fixation with percutaneous pedicle screw instrumentation. Lumbar function was measured using Oswestry Disability Index, and pain was measured with visual analog scale. Fusion and subsidence were also recorded.The study included 5 female and 2 male patients. The median age was 58.9 years. The duration of follow-up was 31.8 ±â€Š6.1 months (range: 24-47). All patients recovered from the infection without relapse within 24-month follow-up. Visual analog scale significantly declined from 7.57 ±â€Š0.53 before surgery to 1.57 ±â€Š0.53 at 12-month follow-up. Mean Oswestry Disability Index decreased from 72.14 ±â€Š6.82 before surgery to 22.28 ±â€Š2.13 after surgery. All patients had solid fusion at 2-year follow-up. Fusion occurred at 6 to 15 months (mean 9.8 months).The specific use of PEEK cages in lumbar polymicrobial spondylodiscitis suggests reliable outcome in terms of clinical and imaging outcomes in our limited cases.


Assuntos
Transplante Ósseo/métodos , Coinfecção/cirurgia , Discite/cirurgia , Cetonas/química , Vértebras Lombares/cirurgia , Polietilenoglicóis/química , Fusão Vertebral/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Parafusos Pediculares , Estudos Retrospectivos
8.
Eur J Med Chem ; 192: 112160, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32146375

RESUMO

A series of tripeptidic proteasome inhibitors with furylketone as C-terminus were designed and synthesized. Biochemical evaluations against ß1, ß2 and ß5 subunits revealed that they acted selectively on ß5 subunit with IC50s against chymotrypsin-like (CT-L) activity in micromolar range. LC-MS/MS analysis of the ligand-20S proteasome mixture showed that the most potent compound 11m (IC50 = 0.18 µM) made no covalent modification on 20S proteasome. However, it was identified acting in a slowly reversible manner in wash-out assay and the reversibility was much lower than that of MG132, suggesting the possibility of these tripeptidic furylketones forming reversible covalent bonds with 20S proteasome. Several compounds were selected for anti-proliferative assay towards multiple cancer cell lines, and compound 11m displayed comparable potency to positive control (MG132) in all cell lines tested. Furthermore, the pharmacokinetic (PK) data in rats indicated 11m behaved similarly (Cmax, 2007 µg/L; AUC0-t, 680 µg/L·h; Vss, 0.66 L/kg) to the clinical used agent carfilzomib. All these data suggest 11m is a good lead compound to be developed to novel anti-tumor agent.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Furanos/farmacologia , Cetonas/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/síntese química , Furanos/química , Células HCT116 , Humanos , Cetonas/síntese química , Cetonas/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Inibidores de Proteassoma/síntese química , Inibidores de Proteassoma/química , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
9.
Biochem J ; 477(7): 1323-1344, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32202613

RESUMO

Metacaspases are novel cysteine proteases found in apicomplexan whose function is poorly understood. Our earlier studies on Plasmodium falciparum metacaspase-2 (PfMCA-2) revealed that the caspase inhibitor, Z-FA-FMK efficiently inhibited PfMCA-2 activity and, expression, and significantly blocked in vitro progression of the parasite developmental cycle via apoptosis-like parasite death. Building on these findings, we synthesized a set of novel inhibitors based on structural modification of Z-FA-FMK with the amides of piperic acid and investigated their effect on PfMCA-2. One of these analogs, SS-5, specifically inhibited the activity and expression of PfMCA-2. The activities of some other known malarial proteases (falcipains, plasmepsins and vivapain), and human cathepsins-B, D and L, and caspase-3 and -7 were not inhibited by SS-5. SS-5 blocked the development of P. falciparum in vitro (IC50 1 µM) and caused prominent morphological distortions. Incubation with SS-5 led to persistent parasite oxidative stress accompanied by depolarization of mitochondrial potential and accumulation of intracellular Ca2+. SS-5 also inhibited the development of P. berghei in a murine model. Our results suggest that the inhibition of PfMCA-2 results in oxidative stress, leading to apoptosis-like parasite death. Thus, SS-5 offers a starting point for the optimization of new antimalarials, and PfMCA-2 could be a novel target for antimalarial drug discovery.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/farmacologia , Dipeptídeos/farmacologia , Cetonas/farmacologia , Plasmodium falciparum/enzimologia , Amidas/química , Animais , Antimaláricos/química , Antimaláricos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Sobrevivência Celular/efeitos dos fármacos , Dipeptídeos/química , Descoberta de Drogas/métodos , Ácidos Graxos Insaturados/química , Feminino , Células Hep G2 , Humanos , Cetonas/química , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos
10.
J Vis Exp ; (156)2020 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-32116307

RESUMO

Heteroarylation introduces heteroaryl fragments to organic molecules. Despite the numerous available reactions reported for arylation via transition metal catalysis, the literature on direct heteroarylation is scarce. The presence of heteroatoms such as nitrogen, sulfur and oxygen often make heteroarylation a challenging research field due to catalyst poisoning, product decomposition and the rest. This protocol details a highly efficient direct α-C(sp3) heteroarylation of ketones under microwave irradiation. Key factors for successful heteroarylation include the use of XPhos Palladacycle Gen. 4 Catalyst, excess base to suppress side reactions and the high temperature and pressure achieved in a sealed reaction vial under microwave irradiation. The heteroarylation compounds prepared by this method were fully characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR) and high-resolution mass spectrometry (HRMS). This methodology has several advantages over literature precedents including broad substrate scope, rapid reaction time, greener procedure and operational simplicity by eliminating the preparation of intermediates such as silyl enol ether. Possible applications for this protocol include, but are not limited to, diversity-oriented synthesis for the discovery of biologically active small molecules, domino synthesis for the preparation of natural products and ligand development for new transition metal catalytic systems.


Assuntos
Cetonas/síntese química , Metais/química , Micro-Ondas , Elementos de Transição/química , Compostos Inorgânicos de Carbono/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Catálise , Cromatografia , Cetonas/química , Paládio/química , Espectroscopia de Prótons por Ressonância Magnética , Compostos de Silício/química , Temperatura
11.
Org Lett ; 22(4): 1575-1579, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32013447

RESUMO

An efficient one-pot synthesis of 4-(1H)-quinolones through an orthogonal engagement of diverse o-haloaryl ynones with ammonia in the presence of Cu(I), involving tandem Michael addition and ArCsp2-N coupling, is presented. The substrate scope of this convenient protocol, wherein ammonium carbonate acts as both an in situ ammonia source and a base toward diverse 2-substituted 4-(1H)-quinolones, has been mapped and its efficacy validated through concise total synthesis of bioactive natural products pseudanes (IV, VII, VIII, and XII), graveoline, graveolinine, and waltherione F.


Assuntos
Amônia/química , Cetonas/química , Metoxaleno/análogos & derivados , Quinolinas/síntese química , Quinolonas/síntese química , Metoxaleno/síntese química , Metoxaleno/química , Estrutura Molecular , Quinolinas/química , Quinolonas/química
12.
Molecules ; 25(4)2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085624

RESUMO

Dialkyl diketene dimers are used as sizing agents in the manufacture of paper and board for food contact applications to increase wetting stability. Unbound residues can hydrolyze and decarboxylate into dialkylketones. These non-intentionally added substances (NIAS) have potential to migrate to fatty foods in contact with those packaging materials. In Germany, the Federal Institute for Risk Assessment (BfR) established a specific migration limit (SML) of 5 mg/kg for the transfer of these dialkylketones into foodstuffs. In order to investigate the differences between simulants and real foods, an analytical method was optimized for extraction and quantification of dialkylketones in edible oils and fatty foods by gas chromatography coupled with flame ionization detection (GC-FID), and additionally by gas chromatography with mass spectrometry (GC-MS), to confirm their identification and to quantify them in case of interferences. Dialkylketones are separated from the extracted fat by alkaline saponification of the triglycerides. Dialkylketones migration from paper-based food contact articles into organic solvents isooctane and dichloromethane, in olive and sunflower oils, and in fatty foods (croissants, Gouda, cheddar cheese, and salami was studied). As a result, it was found that the simulating tests, including the edible oil extraction tests, gave migration values that exceeded the SML largely, while the migration with the food samples were largely below the SML.


Assuntos
Embalagem de Alimentos , Alimentos , Cetonas/química , Lipídeos/química , Papel , Calibragem , Dimerização , Ionização de Chama , Cromatografia Gasosa-Espectrometria de Massas , Hidrólise , Reprodutibilidade dos Testes , Solventes/química
13.
Molecules ; 25(4)2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32102166

RESUMO

A family of complexes of the formula trans-[RuCl2(L)(R-pybox)] (R-pybox = (S,S)-iPr-pybox, (R,R)-Ph-pybox, L = monodentate phosphonite, PPh(OR)2, and phosphinite, L = PPh2(OR), ligands) were screened in the catalytic asymmetric transfer hydrogenation of acetophenone, observing a strong influence of the nature of both the R-pybox substituents and the L ligand in the process. The best results were obtained with complex trans-[RuCl2{PPh2(OEt)}{(R,R)-Ph-pybox}] (2c), which provided high conversion and enantioselectivity (up to 96% enantiomeric excess, e.e.) for the reduction of a variety of aromatic ketones, affording the (S)-benzylalcohols.


Assuntos
Cetonas/química , Oxazóis/química , Compostos de Fósforo/química , Piridinas/química , Rutênio/química , Acetofenonas/química , Catálise , Complexos de Coordenação/química , Cristalografia por Raios X , Hidrogenação , Isomerismo , Ligantes , Fosfinas/química , Fosfitos/química
14.
Molecules ; 25(3)2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033188

RESUMO

A series of D-π-A diketopyrrolopyrrole(DPP)-based small molecules were designed for organic light-emitting diode(OLEDs) and organic solar cell(OSCs) applications. Applying the PBE0/6-31G(d,p) method, the ground state geometry and relevant electronic properties were investigated. The first excited singlet state geometry and the absorption and fluorescent spectra were simulated at the TD-PBE0/6-31G(d,p) level. The calculated results revealed that the photophysical properties were affected through the introduction of different end groups. Furthermore, the electronic transitions corresponding to absorption and emission exhibited an intramolecular charge transfer feature. Our results suggest that the designed molecules acted not only as luminescent for OLEDs, but also as donor materials in OSCs. Moreover, they can also be used as potential electron transfer materials for OLEDs and OSCs.


Assuntos
Cetonas/química , Luminescência , Substâncias Luminescentes/química , Pirróis/química , Eletrônica , Lasers Semicondutores , Modelos Moleculares , Energia Solar
15.
Nat Commun ; 11(1): 672, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015335

RESUMO

The C-C σ-bond activation of unstrained cycloketones represents an ingenious and advanced technique in synthetic chemistry, but it remains a challenging area which has been largely underexplored. Herein we report an efficient strategy for the direct C-C cleavage of cyclohexanones and cyclopentanones. The cyclic C-C σ-bond is readily cleaved under mild conditions with the aid of an in situ formed side-chain aryl radical. Density functional theory calculations are carried out to shed light on the unusual regioselectivity of C-C bond cleavage. The reaction affords a variety of structurally diverse 3-coumaranones and indanones that widely exist in natural products and bioactive molecules, illustrating the synthetic value of this method.


Assuntos
Carbono/química , Cetonas/química , Produtos Biológicos/química , Cicloexanonas/química , Ciclopentanos/química , Modelos Moleculares , Estrutura Molecular
16.
Chemistry ; 26(14): 3173-3180, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32083355

RESUMO

Development of novel bioimaging materials that exhibit organelle specific accumulation continues to be at the forefront of research interests and efforts. Among the various subcellular organelles, mitochondria, which are found in the cytoplasm of eukaryotic cells, are of particular interest in relation to their vital function. To date, most molecular probes that target mitochondria utilise delocalised lipophilic cations such as triphenylphosphonium and pyridinium. However, the use of such charged motifs is known to be detrimental to the working function of the mitochondrial transmembrane potential and there remains a strong case for development of neutral mitochondrial fluorescent probes. Herein, we demonstrate for the first time the exploitation of diketopyrrolopyrrole-based chemistries for the realisation of a neutral fluorescent probe that exhibits organelle specific accumulation within the mitochondria at the nanomolar level. The synthesised probe, which bears a neutral triphenylphosphine oxide moiety, exhibits a large Stokes shift and high fluorescence quantum yield in water, both highly sought-after properties in the development of bioimaging agents. In vitro studies reveal no interference with cell metabolism when tested for the human MCF7 breast cancer cell and nanomolar subcellular organelle colocalisation with commercially available mitochondrial staining agent Mitotracker Red. In light of its novelty, neutral structure and the preferential accumulation at nanomolar concentrations we anticipate this work to be of significant interest for the increasingly larger community devoted to the realisation of neutral mitochondrial selective systems and more widely to those engaged in the rational development of superior organic architectures in the biological field.


Assuntos
Corantes Fluorescentes/química , Cetonas/química , Mitocôndrias/metabolismo , Compostos Organofosforados/química , Pirróis/química , Técnicas Biossensoriais , Humanos , Luz , Células MCF-7 , Potencial da Membrana Mitocondrial/fisiologia , Estrutura Molecular , Imagem Óptica , Compostos Orgânicos/química , Relação Estrutura-Atividade
17.
Chem Commun (Camb) ; 56(21): 3119-3122, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32090223

RESUMO

A highly efficient diastereoselective transfer hydrogenation of α-aminoalkyl α'-chloromethyl ketones catalyzed by a tethered rhodium complex was developed and successfully utilized in the synthesis of the key intermediates of HIV protease inhibitors. With the current Rh(iii) catalyst system, a series of chiral 3-amino-1-chloro-2-hydroxy-4-phenylbutanes were produced in excellent yields and diastereoselectivities (up to 99% yield, up to 99 : 1 dr). Both diastereomers of the desired products could be efficiently accessed by using the two enantiomers of the Rh(iii) catalyst.


Assuntos
Complexos de Coordenação/química , Cetonas/química , Ródio/química , Catálise , Inibidores da Protease de HIV/síntese química , Hidrogenação , Ligantes , Estrutura Molecular , Oxirredução , Estereoisomerismo , Relação Estrutura-Atividade
18.
Luminescence ; 35(4): 572-579, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31908148

RESUMO

Two new difluoroboron ß-carbonyl cyclic ketonate complexes C2B and DC2B were investigated using several spectroscopic methods. Relative to the absorption spectra, the fluorescence spectra were more affected by the polarity of the solvent. Also, compound C2B showed a more pronounced Stokes' shift after solvent polarity increased. Transient absorption measurements then demonstrated the relaxation behaviour of the excited state compound molecule. The kinetic results showed that the excited state C2B in tetrahydrofuran (THF) can return from the intramolecular charge-transfer (ICT) state and the initial excited state to the ground state. The kinetic relaxation pathway after THF was replaced by dimethyl sulfoxide became single. When the carbazole unit was introduced, DC2B also exhibited an ICT state but there was no significant difference in the excited state relaxation path after solvent polarity was changed. The results indicated that C2B is more susceptible to solvent polarity regulation. The global fit results revealed that an increase in the solvent polarity prolonged the lifetime of the ICT state of compound C2B and had the opposite effect on compound DC2B. These results provide guidance for understanding the relationship between solvent polarity and the designing and synthesizing advanced compound materials.


Assuntos
Compostos de Boro/química , Carbazóis/química , Furanos/química , Cetonas/química , Compostos de Boro/síntese química , Cetonas/síntese química , Fenômenos Ópticos , Solventes/química , Espectrometria de Fluorescência
19.
J Phys Chem A ; 124(7): 1353-1361, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31985229

RESUMO

The microwave spectrum of heptan-2-one (CH3COC4H8CH3) was recorded in the frequency range from 2 to 40 GHz using two molecular jet Fourier transform microwave spectrometers. The two energetically most favorable conformers could be identified and fitted with standard deviations close to measurement accuracy. The splittings arising from the internal rotations of two methyl groups, the acetyl methyl group CH3CO- and the pentyl methyl group -C4H8CH3, could be resolved. The barriers to internal rotation of the acetyl methyl group are 185.666(14) and 233.418(32) cm-1 for conformer I and II, respectively, and can be linked to their specific geometries. For the pentyl methyl group, the respective barrier heights are 982.22(86) and 979.2(21) cm-1.


Assuntos
Cetonas/química , Micro-Ondas , Feromônios/química , Teoria da Densidade Funcional , Gases/química , Estrutura Molecular , Rotação
20.
Molecules ; 25(2)2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31963465

RESUMO

Hf(OTf)4 was identified as a highly potent catalyst (0.1-0.5 mol%) for three-component Mannich reaction under solvent-free conditions. Hf(OTf)4-catalyzed Mannich reaction exhibited excellent regioselectivity and diastereoselectivity when alkyl ketones were employed as substrates. 1H NMR tracing of the H/D exchange reaction of ketones in MeOH-d4 indicated that Hf(OTf)4 could significantly promote the keto-enol tautomerization, thereby contributing to the acceleration of reaction rate.


Assuntos
Háfnio/química , Cetonas/química , Mesilatos/química , Catálise , Bases de Mannich/química , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Solventes
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