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A convenient and efficient synthesis of structurally diverse indazolo[1,2-a]indazolones via a Rh(III)-catalyzed [4 + 1] annulation of 1-arylindazolones with alkynyl cyclobutanols has been achieved by combining C-H and C-C bond cleavage. This cascade reaction features readily available starting materials, good functional group tolerance, broad substrate scope, and excellent atom-economy.
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Two new cationic meso-thiazolium-BODIPY-based water-soluble and red-shifted fluorescent probes were constructed for the first time. They can monitor cellular viscosity in dual organelles and show aggregation-induced emission (AIE), which is ascribed to the efficient restricted rotation of meso-thiazolium in viscous or hindered systems. Probe 3 with an N-benzyl group shows better AIE as compared to probe 2 with an N-methyl group.
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Epilepsy is a complex disease in the brain. Complete control of seizure has always been a challenge in epilepsy treatment. Currently, clinical management primarily involves pharmacological and surgical interventions, with the former being the preferred approach. However, antiepileptic drugs often exhibit low bioavailability due to inherent limitations such as poor water solubility and difficulty penetrating the blood-brain barrier (BBB). These issues significantly reduce the drugs' effectiveness and limit their clinical application in epilepsy treatment. Additionally, the diagnostic accuracy of current imaging techniques and electroencephalography (EEG) for epilepsy is suboptimal, often failing to precisely localize epileptogenic tissues. Accurate diagnosis is critical for the surgical management of epilepsy. Thus, there is a pressing need to enhance both the therapeutic outcomes of epilepsy medications and the diagnostic precision of the condition. In recent years, the advancement of nanotechnology in the biomedical sector has led to the development of nanomaterials as drug carriers. These materials are designed to improve drug bioavailability and targeting by leveraging their large specific surface area, facile surface modification, ability to cross the BBB, and high biocompatibility. Furthermore, nanomaterials have been utilized as contrast agents in imaging and as materials for EEG electrodes, enhancing the accuracy of epilepsy diagnoses. This review provides a comprehensive examination of current research on nanomaterials in the treatment and diagnosis of epilepsy, offering new strategies and directions for future investigation.
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Cellular senescence is characterized by the permanent arrest of cell proliferation and is a response to endogenous and exogenous stress. The continuous accumulation of senescent cells (SnCs) in the body leads to the development of aging and age-related diseases (such as neurodegenerative diseases, cancer, metabolic diseases, cardiovascular diseases, and osteoarthritis). In the face of the growing challenge of aging and age-related diseases, several compounds have received widespread attention for their potential to target SnCs. As a result, senolytics (compounds that selectively eliminate SnCs) and senomorphics (compounds that alter intercellular communication and modulate the behavior of SnCs) have become hot research topics in the field of anti-aging. In addition, strategies such as combination therapies and immune-based approaches have also made significant progress in the field of anti-aging therapy. In this article, we discuss the latest research on anti-aging targeting SnCs and gain a deeper understanding of the mechanism of action and impact of different anti-aging strategies on aging and age-related diseases, with the aim of providing more effective references and therapeutic ideas for clinical anti-aging treatment in the face of the ever-grave challenges of aging and age-related diseases.
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A one-pot three-component synthesis of multifunctionalized isoquinolones from 2-oxazolines, iodonium ylides, and carboxylic acids via Rh(III)-catalyzed oxazolinyl-directed C-H activation and tandem annulation under redox-neutral conditions has been developed. This catalytic system is characterized by readily available starting materials, a wide tolerance of functional groups, a short reaction time, and high yields. The synthetic utility of the cascade reaction was further demonstrated by a gram-scale synthesis and derivatization of the obtained products.
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Hypochlorous acid/hypochlorite (HOCl/ClO-) plays important roles in killing bacterial and causing damage to living tissues, and its abnormal levels could lead to many diseases. Although great efforts have been devoted, fluorescent probes for HOCl/ClO- with near-infrared fluorescence, good selectivity/sensitivity, and low background are still important and urgent. In this work, a novel double-bond-linked TCF-aza-BODIPY-based near-infrared fluorescent probe (3) was rationally designed, successfully prepared, and applied for sensing HOCl/ClO- in both solutions and living RAW264.7 cells, showing good selectivity and fluorescence "turn-on" phenomenon at 670 nm with low background. The limit of detection towards ClO- was determined to be 0.36 µM through the linear fluorescence changes at 670 nm in a broad ClO--concentration range of 0-150 µM. Furthermore, the sensing mechanism was investigated by mass spectrometry and compared with 1, suggesting that the remarkable spectroscopic changes could be ascribed to the oxidization of the double bond to the aldehyde group, accompanied with the leaving of the TCF group. Confocal imaging experiments also confirmed the remarkable intracellular fluorescence enhancements through incubation of ClO- and phorbol ester 12-myristate 13-acetate (PMA) in RAW264.7 cells. Therefore, for the first time, we reported a near-infrared TCF-aza-BODIPY-based fluorescent probe for highly sensitive and fluorescence "turn-on" detection of both exogenous and endogenous HOCl in living RAW264.7 cells through the quick oxidation of a conjugated double bond.
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Corantes Fluorescentes , Ácido Hipocloroso , Compostos de Boro/química , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Microscopia de Fluorescência/métodosRESUMO
With increasing demand for customized commodities and the greater insight and understanding of olfaction, the synthesis of fragrances with diverse structures and odor characters has become a core task. Recent progress in organic synthesis and catalysis enables the rapid construction of carbocycles and heterocycles from readily available unsaturated molecular building blocks, with increased selectivity, atom economy, sustainability and product diversity. In this review, synthetic methods for creating cyclic fragrances, including both natural and synthetic ones, will be discussed, with a focus on the key transformations of alkenes, alkynes, dienes and enynes. Several strategies will be discussed, including cycloaddition, catalytic cyclization, ring-closing metathesis, intramolecular addition, and rearrangement reactions. Representative examples and the featured olfactory investigations will be highlighted, along with some perspectives on future developments in this area.
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Alcenos , Alcinos , Alcenos/química , Alcinos/química , Catálise , Ciclização , Reação de Cicloadição , OdorantesRESUMO
Two novel meso-CF3 BODIPY-based fluorescent rotors have been rationally prepared and found to sensitively respond to viscosity in living cells with a fluorescence "turn-on" effect, attributed to the special restricted rotation of meso-CF3 group in viscous environments. Interestingly, a monostyryl probe with one cationic group exhibits good mitochondrial localization and AIE property.
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Compostos de Boro/química , Corantes Fluorescentes/química , Mitocôndrias/metabolismo , Viscosidade , Cátions , Células HeLa , Humanos , Estrutura Molecular , Espectrometria de FluorescênciaRESUMO
An efficient rhodium(III)-catalyzed direct C-H oxidative annulation of isoquinolones with allyl alcohols as C1 synthons has been successfully developed. This protocol enables the straightforward synthesis of structurally diverse isoindolo[2,1-b]isoquinolin-5(7H)-ones with high atom economy, tolerates a broad spectrum of functionalities, and is applicable to one-pot operation from readily available N-methoxybenzamides.
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Hydrogen peroxide (H2O2) plays vital roles in oxidative stress and signal transduction in living organisms, and its abnormal levels could be linked to many diseases. Despite numerous efforts spent, it is still urgent and of high importance to develop better H2O2 probes with good selectivity, high sensitivity and low backgrounds. To this end, a novel boron dipyrromethene (BODIPY)-based fluorescent probe with an electron-withdrawing methylenemalononitrile at the meso position has been rationally designed, successfully synthesized and investigated for detection of H2O2 in aqueous solutions and living cells, which exhibited high selectivity and sensitivity, fluorescent "turn-on" phenomenon at 540 nm, and ratiometric changes from 506 to 540 nm. Upon exposure to H2O2, a strong fluorescent emission at 540 nm appeared and the corresponding quantum yields changed from 0.009 to 0.13. The detection limit towards H2O2 was calculated to be 31 nM by the linear fluorescence change at 540 nm in the H2O2-concentration ranging from 2 to 10 µM. This probe was applicable in a pH range from 6 to 10. Meanwhile, the sensing mechanism was also confirmed by the 1H NMR and mass spectrometry, suggesting that the above changes might be ascribed to the quick addition and oxidization of the double bond. Furthermore, confocal imaging results also showed great enhancement of intracellular fluorescence upon exposure to H2O2 and PMA in RAW264.7 cells, unambiguously confirming its great potentials as a fluorescent probe for highly sensitive detection of both exogenous and endogenous H2O2 in living cells.
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Compostos de Boro/química , Corantes Fluorescentes/química , Peróxido de Hidrogênio/análise , Nitrilas/química , Imagem Óptica , Animais , Relação Dose-Resposta a Droga , Corantes Fluorescentes/síntese química , Células HEK293 , Humanos , Camundongos , Estrutura Molecular , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
The synthesis of C3-substituted isoindolin-1-ones from oxazolines and cyclopropanols has been achieved with oxazoline as a bifunctional nucleophilic directing group. The reaction proceeds by the cleavage of three chemical bonds and allows the formation of three new chemical bonds, a C-N bond, a C-C bond, and a C-O bond, in a single step.
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Correction for 'Rhodium(iii)-catalyzed oxidative alkylation of N-aryl-7-azaindoles with cyclopropanols' by Jidan Liu et al., Org. Biomol. Chem., 2021, DOI: .
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An efficient Rh(iii)-catalyzed C-H oxidative alkylation of N-aryl-7-azaindoles with cyclopropanols by merging tandem C-H and C-C cleavage was developed. This transformation features mild reaction conditions, high regioselectivity, and excellent functional group compatibility. The resulting ß-aryl ketone derivatives can be readily transformed into 7-azaindole-containing π-extended polycyclic heteroarenes.
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A new near-infrared (NIR)-emitting aza-boron-dipyrromethene dye with two electron-donating amino groups at 1- and 7-positions has been prepared via several steps of reactions. This probe showed a NIR absorption at 748 nm with an obvious shoulder peak at 634 nm in CH3CN/H2O. Interestingly, a NIR fluorescence emission at 843 nm was observed with a large Stokes shift of 95 nm. This novel NIR-emitting aza-boron-dipyrromethene dye was further investigated as a Hg2+-sensing fluorescent probe, which selectively bound to Hg2+, showing a blue-shifted and sharp absorption band at 695 nm with the disappearance of the shoulder peak at 634 nm. Correspondingly, the color change could be easily seen from blue to green. Interestingly, the emission exhibited an absolutely "turn-on" peak at 725 nm with a significant blue shift by 118 nm (from 843 to 725 nm), due to the efficient inhibition of the intramolecular-charge-transfer process arising from two amino groups. This probe was finally introduced to Hela cells, showing a "OFF-ON" NIR emission upon exposure to Hg2+. The overall results confirmed that this novel NIR-emitting aza-boron-dipyrromethene fluorescent probe with a large Stokes shift could serve as a colorimetric and fluorescent "turn-on" sensor for Hg2+ in both solutions and living cells.
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Corantes Fluorescentes , Mercúrio , Boro , Compostos de Boro , Células HeLa , Humanos , Porfobilinogênio/análogos & derivadosRESUMO
Polycyclic scaffolds are omnipresent in natural products and drugs, and the synthetic strategies and methods toward construction of these scaffolds are of particular importance. Compared to simple cyclic ring systems, polycyclic scaffolds have higher structure complexity and diversity, making them suitable for charting broader chemical space, yet bringing challenges for the syntheses. In this review, we surveyed progress in the past decade on synthetic methods for polycyclic natural product scaffolds, in which the key steps are one-pot reactions involving intermolecular or intramolecular alkyne annulation. Synthetic strategies of selected polycyclic carbocycles and heterocycles with at least three fused, bridged, or spiro rings are discussed with emphasis on the synthetic efficiency and product diversity. Recent examples containing newly developed synthetic concepts or toolkits such as collective and divergent total synthesis, gold catalysis, C-H functionalization, and dearomative cyclization are highlighted. Finally, several "privileged synthetic strategies" for "privileged polycyclic scaffolds" are summarized, with discussion of remained challenges and future perspectives.
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A general method for the synthesis of structurally diverse N-arylpyrazoles from readily available cyclopropanols and aryldiazonium salts is disclosed. The reaction was conducted at room temperature within minutes with a broad substrate scope and excellent regioselectivity.
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An enantioselective organocatalytic desymmetrization of 2,2-disubstituted cyclopentene-1,3-diones via a formal C(sp2)-H amidation is reported. The reaction was carried out with N-methoxy amide as the nitrogen source and commercially available cinchonidine as the catalyst under mild reaction conditions, releasing methanol as the only byproduct. It provides an efficient way to synthesize enantioenriched chiral cyclopentenyl amines bearing an all-carbon quaternary stereogenic carbon center.
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An efficient [2 + 2 + 2] benzannulation of phthalic acids/anhydrides with two alkynes was developed for synthesis of multisubstituted 1-naphthoic acids via Ru-catalyzed C-H activation. The reaction preceded well using atmospheric oxygen as the sole oxidant with high atom/step economies. Facilitated by the free carboxyl group, the products can be easily converted to diverse polycyclic molecules.
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A near-infrared distyryl boron dipyrromethene-based sensor bearing one bis(1,2,3-triazole)amino receptor has been synthesized. This probe selectively and quickly binds to Hg2+ and Cu2+ ions in CH3CN/H2O (5:1â¯v/v) and exhibits remarkably blue-shifted absorption and fluorescence bands due to the inhibition of the intramolecular charge transfer process. The fluorescence changes of this probe upon binding to Hg2+ or Cu2+ ion are totally different, undergoing a ratiometric fluorescence enhancement (for Hg2+) or a fluorescence quenching (for Cu2+) mechanism. The corresponding vivid color changes can be easily seen by the naked eye. This probe was further introduced into Hela cells for living cell imaging and found to discriminate Hg2+ and Cu2+ ions through two near-infrared fluorescence emission channels. These overall results indicate that this Click-derived near-infrared BODIPY-based probe is potentially useful for ratiometric and discriminative detection of Hg2+ and Cu2+ ions in solutions and living cells.
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Compostos de Boro/química , Cobre/análise , Corantes Fluorescentes/química , Mercúrio/análise , Células HeLa , Humanos , Raios Infravermelhos , Íons/análise , Células Tumorais CultivadasRESUMO
A simple and efficient approach has been developed for the synthesis of imidazo[1,5-a]pyridines using the elemental sulfur mediated sequential dual oxidative Csp3-H amination of 2-pyridyl acetates and amines under metal- and peroxide-free conditions. Broad substrate scope, operational simplicity and gram-scale ability make this chemistry very practical.