RESUMO
Many diseases in the human body are related to the overexpression of viscosity and sulfur dioxide. Therefore, it is essential to develop rapid and sensitive fluorescent probes to detect viscosity and sulfur dioxide. In the present work, we developed a dual-response fluorescent probe (ES) for efficient detection of viscosity and sulfur dioxide while targeting mitochondria well. The probe generates intramolecular charge transfer by pushing and pulling the electron-electron system, and the ICT effect is destroyed and the fluorescence quenched upon reaction with sulfite. The rotation of the molecule is inhibited in the high-viscosity system, producing a bright red light. In addition, the probe has good biocompatibility and can be used to detect sulfite in cells, zebrafish and mice, as well as upregulation of viscosity in LPS-induced inflammation models. We expect that the dual response fluorescent probe ES will be able to detect viscosity and sulfite efficiently, providing an effective means of detecting viscosity and sulfite-related diseases.
Assuntos
Corantes Fluorescentes , Inflamação , Mitocôndrias , Sulfitos , Peixe-Zebra , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Animais , Sulfitos/química , Sulfitos/análise , Viscosidade , Mitocôndrias/metabolismo , Mitocôndrias/química , Camundongos , Humanos , Inflamação/induzido quimicamente , Dióxido de Enxofre/análise , Dióxido de Enxofre/química , Lipopolissacarídeos , Células RAW 264.7 , Imagem Óptica/métodosRESUMO
Biothiols play a crucial role in maintaining redox balance in organisms, and anomalous levels of biothiols in human organs can lead to various sicknesses and biological disorders. This work developed a novel sensitive fluorescent probe TZ-NBD with double channels for highly efficient recognition of biothiols. TZ-NBD adopts 4-Chloro-7-nitrobenzofurazan (NBD-Cl) as the recognition moiety with simultaneous fluorescence output. By incorporating NBD-Cl with the other fluorophore, benzothiazole dihydrocyclopentachromene derivative (TZ-OH), the dual-channel sensitive fluorescence probe TZ-NBD was built. The existence of Cys/ Hcy could significantly trigger both the green and red fluorescent emissions, which were derived from fluorophores amine-substituted NBD and TZ-OH, respectively. While exposing to GSH, only the red-channel fluorescence signal could be detected, indicating the release of TZ-OH. The phenomena was mainly attributed to the fact that sulfur-substituted NBD has nearly no fluorescence, while amine-substituted NBD shows obvious green fluorescence. In our study, TZ-NBD exhibited dual-channel sensitivity, fast response, and excellent selectivity to biothiols in vitro. Moreover, TZ-NBD was favorably utilized for recognition of biothiols in vivo. We believe that the sensitive fluorescence probe with double channels can afford an alternate approach for monitoring biothiols in organisms and would be useful for studying diseases associated with biothiols.
Assuntos
Cisteína , Corantes Fluorescentes , Humanos , Glutationa , Espectrometria de Fluorescência , Aminas , HomocisteínaRESUMO
Biothiols, including cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), play distinct yet crucial roles in various mitochondrial physiological activities. However, due to their similar chemical structures, distinguishing and detecting Cys/Hcy/GSH poses a considerable challenge. In this study, we developed a dual-channel, mitochondrial-targeted fluorescent probe termed QX-NBD, designed specifically for discriminating Cys/Hcy from GSH. The incorporation of a quinolinium group endowed the probe with excellent mitochondrial targeting capabilities. This functionality arose from the positively charged group's ability to selectively bind to negatively charged mitochondrial membranes through electrostatic interactions. Additionally, the ether bond between 4-chloro-7-nitro-1,2,3-benzoxadiazole and the near-infrared fluorophore QX-OH rendered the probe susceptible to nucleophilic attack by biothiols. Upon the introduction of Cys/Hcy, the probe exhibited dual fluorescence emissions in red and green. Conversely, the presence of GSH resulted in only red fluorescence emission. The detection limits of the probe for Cys and Hcy at 542 nm in buffer solution were determined to be 0.044 µM and 0.042 µM, respectively. Similarly, the detection limit for all these biothiols was 0.028 µM at 678 nm. Furthermore, the response times for Cys/Hcy/GSH were recorded as 4.0 min, 5.5 min, and 9.5 min, respectively. Moreover, the probe was employed to monitor fluctuations in biothiol levels during oxidative stress in both HeLa cells and zebrafish, demonstrating its applicability and utility in biological contexts.
Assuntos
Corantes Fluorescentes , Homocisteína , Mitocôndrias , Peixe-Zebra , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Animais , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/química , Células HeLa , Homocisteína/análise , Homocisteína/metabolismo , Homocisteína/análogos & derivados , Compostos de Sulfidrila/análise , Compostos de Sulfidrila/química , Glutationa/análise , Glutationa/metabolismo , Cisteína/análise , Espectrometria de Fluorescência/métodos , Limite de Detecção , Imagem Óptica/métodosRESUMO
Hydroxyl radical (â¢OH), one of the most reactive and deleterious substances in organisms, belongs to a class of reactive oxygen species (ROS), and it has been verified to play an essential role in numerous pathophysiological scenarios. However, due to its extremely high reactivity and short lifetime, the development of a reliable and robust method for tracking endogenous â¢OH remains an ongoing challenge. In this work, we presented the first ratiometric fluorescent nanoprobe NanoDCQ-3 for â¢OH sensing based on oxidative C-H abstraction of dihydroquinoline to quinoline. The study mainly focused on how to modulate the electronic effects to achieve an ideal ratiometric detection of â¢OH, as well as solving the inherent problem of hydrophilicity of the probe, so that it was more conducive to monitoring â¢OH in living organisms. The screened-out probe NanoDCQ-3 exhibited an exceptional ratiometric sensing capability, better biocompatibility, good cellular uptake, and appropriate in vivo retention, which has been reliably used for detecting exogenous â¢OH concentration fluctuation in living cells and zebrafish models. More importantly, NanoDCQ-3 facilitated visualization of â¢OH and evaluation of drug treatment efficacy in diabetic mice. These findings afforded a promising strategy for designing ratiometric fluorescent probes for â¢OH. NanoDCQ-3 emerged as a valuable tool for the detection of â¢OH in vivo and held potential for drug screening for inflammation-related diseases.
Assuntos
Técnicas Biossensoriais , Diabetes Mellitus Experimental , Animais , Camundongos , Radical Hidroxila , Peixe-Zebra , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Espécies Reativas de Oxigênio , Corantes FluorescentesRESUMO
Benefiting from high spatiotemporal resolution, deep tissue penetration, and excellent sensitivity, fluorescence imaging technology has been widely applied in cancer diagnosis and treatment. In recent years, a large number of fluorescent probes for monitoring the levels of endogenous biothiols have been reported, which have significant implications for cancer diagnosis and treatment. However, most probes still suffer from poor biological compatibility and easy attachment by the environment. This work presents the development of a water-soluble dual-channel fluorescent probe, named MAL-NBD, for sensitively detecting biothiols. Nonfluorescent MAL-NBD is transformed into fluorescent groups MAL and NBD-SR/NR through nucleophilic substitution by biologically active thiols, producing dual-channel fluorescence signals for precise detection of biologically active thiols. Taking advantage of the excellent biocompatibility and low biotoxicity, MAL-NBD is successfully used for imaging HeLa cancer cells and zebrafish larvae, promoting its potential application for the precise detection of biological thiols involved in physiological and pathological processes.
Assuntos
Corantes Fluorescentes , Peixe-Zebra , Humanos , Animais , Compostos de Sulfidrila , Células HeLa , Imagem Óptica/métodosRESUMO
A polymeric monophosphine ligand WePhos has been synthesized and complexed with palladium(ii) acetate [Pd(OAc)2] to generate a thermoresponsive pre-catalyst that can shuttle between water and organic phases, with the change being regulated by temperature. The structure of the polymeric ligand was confirmed with matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry and size-exclusion chromatography (SEC) analysis, as well as nuclear magnetic resonance (NMR) measurements. This polymeric metal complex enables highly efficient Pd-catalyzed cross-couplings and tandem reactions using 50 to 500 ppm palladium, and this can facilitate reactions that are tolerant to a broad spectrum of (hetero)aryl substrates and functional groups, as demonstrated with 73 examples with up to 99% isolated yields. Notably, 97% Pd remained in the aqueous phase after 10 runs of catalyst recycling experiments, as determined via inductively coupled plasma-atomic emission spectrometry (ICP-AES) measurements, indicating highly efficient catalyst transfer. Furthermore, a continuous catalyst recycling approach has been successfully developed based on flow chemistry in combination with the catalyst shuttling behavior, allowing Suzuki-Miyaura couplings to be conducted at gram-scales with as little as 10 ppm Pd loading. Given the significance of transition-metal catalyzed cross-coupling and increasing interest in sustainable chemistry, this work is an important step towards the development of a responsive catalyst, in addition to having high activity, by tuning the structures of the ligands using polymer science.
RESUMO
Highly enantioselective pyridine-directed rhodium-catalyzed asymmetric hydrogenation of challenging 1,1-diarylalkenes is achieved by using [Rh(NBD)DuanPhos]BF4 as a precatalyst. Various types of 2-pyridine substituted 1,1-diarylalkenes could be hydrogenated with good to excellent enantioselectivities, which provide an efficient route to the synthesis of pharmaceutically and biologically active compounds containing a 2-pyridyl ethane unit.