RESUMO
We report a synthetic strategy that allows for the preparation of sterically encumbered heteroleptic Ru(II)porphyrinates with the desired configuration of stable/inert and weak/labile axial ligands to direct reactions between substrates to exclusively occur at the sterically encumbered face. To demonstrate the method, we describe the synthesis of a strapped-Ru(II)porphyrinate bearing a stable/inert triphenylphosphine (PPh3) bulky axial ligand coordinated exo to the central cavity and a weak/labile methanol molecule coordinated at the internal axial position. With this axial ligand configuration, the reported Ru(II)porphyrinate exclusively promotes carbene transfer reactions to olefins through the central cavity, which has been verified by the selective formation of cycloprane-linked [2]rotaxanes.
Assuntos
Alcenos , Ligantes , Modelos MolecularesRESUMO
Research background: Extracts from grape pomace, including the wine, show many biological effects such as antioxidant and anti-inflammatory activities. Unfortunately, winemakers discard the bagasse, so the waste is not exploited, although it contains bioactive compounds with antioxidant and anti-inflammatory properties. The work aims to analyze the hydroethanolic extract of peels from Vitis labrusca agro-industrial waste and to evaluate its antinociceptive and anti-inflammatory properties. This study is relevant for reusing a residue and adding value to the grape economic chain. Experimental approach: A representative sample of pomace was obtained and the peels were used to produce the extract. The phenolic compounds were determined by mass spectrometry in multiple reaction monitoring mode and Folin-Ciocalteu colorimetric method, using gallic acid as standard. The biological analyses were carried out using mice orally treated with crude extract at doses of 30, 100 and 300 mg/kg. We evaluated mechanical hyperalgesia by the von Frey method, thermal heat hyperalgesia using a hot plate at 55 °C, paw edema using a pachymeter, and neutrophil recruitment by measurement of myeloperoxidase activity. The nephrotoxicity and hepatotoxicity were evaluated by biochemical analyses using blood samples that were collected after the Vitis labrusca administration. Results and conclusions: In all wet winemaking residues peel mass fraction was 75%, and in dry residues 59%. We identified nine anthocyanins (3-O-glucosides: peonidin, delphinidin, petunidin and malvidin; 3-p-coumaroyl-glucosides: cyanidin, peonidin, petunidin and malvidin, and malvidin-3,5-diglucoside), five flavonoids (apigenin-7-glucoside, luteolin-7-glucoside, quercetin-3-galactoside, isorhamnetin-3-glucoside and myricetin-3-rutinoside), and mass fraction of phenolic compounds, expressed as gallic acid equivalents, was 26.62 mg/g. In vivo assays showed that Vitis labrusca extract at mass fractions 100 and 300 mg/kg reduced carrageenan-induced mechanical and thermal hyperalgesia, 50% of the paw edema, and neutrophil recruitment. In addition, there were no indications of nephrotoxicity and hepatotoxicity. Our extract obtained from winemaking residue has analgesic and anti-inflammatory properties, related at least in part to the presence of phenolic compounds, and it is not toxic to renal and hepatic tissues. Novelty and scientific contribution: This bio-product can be used as an alternative to synthetic anti-inflammatory agents with the same pharmacological potential and fewer side effects. We demonstrated that Vitis labrusca winemaking waste can be used for the production of antinociceptive and anti-inflammatory products (nutraceutical, pharmaceutical and cosmetics) without toxicity, contributing to the environmental economy.
RESUMO
A simple and fast methodology under microwave irradiation for the synthesis of 2-aminopyrimidine and pyrazole derivatives using Atwal reaction is reported. After the optimization of the reaction conditions, eight 2-aminolpyrimidines containing ferrocene and heterocycles and three ferrocene pyrazoles were synthesized from the respective chalcones in good yields. Eight compounds had their structure determined by X-ray diffraction. The molecular hybrid 6a-h and 9a-c were tested on four cancer cell lines - HCT116, PC3, HL60 and SNB19 - where four pyrimidine 6a, 6f-h and one pyrazole 9c derivatives show promising antiproliferative activity. In addition, docking simulation and machine learning methods were carried out to explain the biological activity achieved by the synthetized compounds.
Assuntos
Antineoplásicos/farmacologia , Compostos Ferrosos/farmacologia , Aprendizado de Máquina , Metalocenos/farmacologia , Micro-Ondas , Simulação de Acoplamento Molecular , Pirazóis/farmacologia , Pirimidinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Ferrosos/síntese química , Compostos Ferrosos/química , Humanos , Metalocenos/síntese química , Metalocenos/química , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-AtividadeRESUMO
Selectivity in N-H and S-H carbene insertion reactions promoted by Ru(II)porphyrinates currently requires slow addition of the diazo precursor and large excess of the primary amine and thiol substrates in the reaction medium. Such conditions are necessary to avoid the undesirable carbene coupling and/or multiple carbene insertions. Here, the authors demonstrate that the synergy between the steric shielding provided by a Ru(II)porphyrinate-based macrocycle with a relatively small central cavity and the kinetic stabilization of otherwise labile coordinative bonds, warranted by formation of the mechanical bond, enables single carbene insertions to occur with quantitative efficiency and perfect selectivity even in the presence of a large excess of the diazo precursor and stoichiometric amounts of the primary amine and thiol substrates. As the Ru(II)porphyrinate-based macrocycle bears a confining nanospace and alters the product distribution of the carbene insertion reactions when compared to that of its acyclic version, the former therefore functions as a nanoreactor.
RESUMO
A 5,15-bis(1,1'-biphenyl)porphyrin-based molecular clip covalently connected to a ditopic aliphatic ester loop moiety yields a semi-rigid macrocycle with a well-defined cavity. The resulting macrocycle fits the structural requirements for the preparation of porphyrinates capable of promoting formation of C-C bonds. To demonstrate the usefulness of porphyrin-based macrocycles, an active-metal-template synthesis of rotaxanes through a redox non-innocent carbene transfer reaction is described. Coordination of CoII ions into the porphyrin subunit followed by addition of appropriate monodentate nitrogen-based additives to function as axial ligands enables the radical carbene transfer reactions to styrene derivatives to occur exclusively through the cavity of the macrocycle to afford cyclopropane-linked rotaxanes in excellent 95 % yield. Investigation of the product distribution afforded from the rotaxane assembly reaction reveals how the redox cooperative action between the carbene species and the CoII ions can be manipulated to gain control over the radical-type mechanism to favor the productive rotaxane forming process.
RESUMO
A CoII /porphyrinate-based macrocycle in the presence of a 3,5-diphenylpyridine axial ligand functions as an endotopic ligand to direct the assembly of [2]rotaxanes from diazo and styrene half-threads, by radical-carbene-transfer reactions, in excellent 95 % yield. The method reported herein applies the active-metal-template strategy to include radical-type activation of ligands by the metal-template ion during the organometallic process which ultimately yields the mechanical bond. A careful quantitative analysis of the product distribution afforded from the rotaxane self-assembly reaction shows that the CoII /porphyrinate subunit is still active after formation of the mechanical bond and, upon coordination of an additional diazo half-thread derivative, promotes a novel intercomponent C-H insertion reaction to yield a new rotaxane-like species. This unexpected intercomponent C-H insertion illustrates the distinct reactivity brought to the CoII /porphyrinate catalyst by the mechanical bond.
RESUMO
Chemical investigation of the tubers of Sinningia allagophylla led to the isolation of two new chromenes, (2S)-12-hydroxylapachenole (1) and (3R)-3,4-dihydro-3-hydroxy-4-oxo-8-methoxylapachenole (2), and three new dimeric chromenes, allagophylldimers A-C (3-5). Thirteen known compounds, 6-methoxy-7,8-benzocoumarin (6), lapachenole, 8-methoxylapachenole, tectoquinone, 7-hydroxytectoquinone, dunniol, α-dunnione, dunnione, 8-hydroxydunnione, aggregatin E, cedrol, oleanolic acid, and halleridone, were also identified. 6-Methoxy-7,8-benzocoumarin (6) has been isolated for the first time from a natural source.
Assuntos
Benzopiranos/isolamento & purificação , Naftalenos/isolamento & purificação , Tubérculos/química , Plantas Medicinais/química , Benzofuranos/química , Benzofuranos/isolamento & purificação , Benzopiranos/química , Brasil , Cicloexanonas/química , Cicloexanonas/isolamento & purificação , Estrutura Molecular , Naftalenos/química , Naftoquinonas/química , Naftoquinonas/isolamento & purificação , Sesquiterpenos Policíclicos , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
A novel series of copper(II) coordination polymers [Cu2(O2CC8H9)4(pyz)]n (1), [Cu2(O2CC8H9)4(dps)]n (2), {[Cu(O2CC8H9)2(dps)(H2O)]·H2O}n (3), {[NaCu(O2CC8H9)2(bpm)(NO3)]·H2O}n (4), and [Cu4(O2CC8H9)6(OH)2(bpp)2]n (5) [O2CC8H9− = 3-phenylpropionate anion, pyz = pyrazine, dps = di(4-pyridyl)sulfide, bpm = 2,2'-bipyrimidine, and bpp = 1,3-bis(4-pyridyl)propane] have been synthesized and magneto-structurally investigated. Compounds 1 and 2 belong to a large group of copper(II) carboxylates where bis-monodentate pyz (1) and dps (2) ligands connect the paddle-wheel [CuII2(µ-O2CC8H9)4] units leading to alternating copper(II) chains. The structure of 3 consists of uniform chains of trans-[CuII(O2CC8H9)2] units linked by the bis-monodentate dps ligand. Compound 4 consists of heterobimetallic chains where [NaI2CuII2(µ-O2CC8H9)4(NO3)2] units are doubly bridged by bis-bidentate bpm ligands. Compound 5 is also a chain compound whose structure is made up by tetranuclear [CuII4(µ3-OH)2(µ-O2CC8H9)4(O2CC8H9)2] units which are doubly bridged by bis-monodentate bpp ligands. The magnetic properties were investigated in the temperature range 1.8300 K. Strong antiferromagnetic interactions across the quadruple synsyn carboxylate are observed in 1 and 2 [J = −378 (1) and −348 cm−1 (2)] whereas a weak ferromagnetic coupling through the double out-of-plane oxo(carboxylate) bridge occurs in 4 [J = +2.66 cm−1], the spin Hamiltonian being defined as H = −JS1·S2 with S1 = S2 = SCu = 1/2. A quasi Curie law is observed for 3 (θ = −0.36 cm−1), the bis-monodentate dps ligand being a very poor mediator of magnetic interactions. The analysis of the magnetic properties of 5 is quite complex because of the presence of two crystallographically independent tetracopper(II) units with single-µ-hydroxo, di-µ-hydroxo, µ3-hydroxo and single-µ-hydroxo plus double syn,syn carboxylate bridges in each one. The nature and values of the magnetic couplings for 5 obtained by fitting (intermediate, strong and weak antiferromagnetic interactions for the three former exchange pathways respectively, and intermediate ferromagnetic interactions for the latter one) were substantiated by DFT type calculations.
RESUMO
Human adipose-derived stem cells (hASCs) are an attractive cell source for therapeutic applicability in diverse fields for the repair and regeneration of damaged or malfunctioning tissues and organs. There is a growing number of cell therapies using stem cells due to their characteristics of modulation of immune system and reduction of acute rejection. So a challenge in stem cells therapy is the delivery of cells to the organ of interest, a specific site. The aim of this paper was to investigate the effects of a supramolecular assembly composed of single-walled carbon nanotubes (SWCNT), molecular magnets (lawsone-Co-phenanthroline), and a synthetic peptide (FWYANHYWFHNAFWYANHYWFHNA) in the hASCs cultures. The hASCs were isolated, characterized, expanded, and cultured with the SWCNT supramolecular assembly (SWCNT-MA). The assembly developed did not impair the cell characteristics, viability, or proliferation. During growth, the cells were strongly attached to the assembly and they could be dragged by an applied magnetic field of less than 0.3 T. These assemblies were narrower than their related allotropic forms, that is, multiwalled carbon nanotubes, and they could therefore be used to guide cells through thin blood capillaries within the human body. This strategy seems to be useful as noninvasive and nontoxic stem cells delivery/guidance and tracking during cell therapy.
Assuntos
Imãs/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Nanotubos de Carbono/química , Peptídeos/química , Tecido Adiposo/citologia , Separação Celular/métodos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Transplante de Células-Tronco Mesenquimais , Nanotubos de Carbono/toxicidade , Naftoquinonas/química , Fenantrolinas/químicaRESUMO
A unique bistable copper-metallacyclic complex is used as an elegant molecular switch for the reversible formation of emulsions by simple pH variation. This switch may have several exciting applications in biphasic processes such as catalysis and separation science technologies.