An interesting ratiometric fluorescent probe with unique optical performance was reported in this work. By modifying on the bridge-head of heptamethine cyanine chromophore with an ...N-phenyl-N’-ethylene amine thiourea substituent as a chemodosimetric recognition unit, the probe exhibited ratiometric fluorescent response towards hypochlorous acid (HClO). Upon addition of HClO, the absorbance spectra showed a great red shift as large as 150nm from 650nm to 800nm. Employing the isosbestic absorption point at 730nm as an excitation wavelength, a ratiometric fluorescent sensing mode with two long emission wavelengths at 760nm and 820nm was acquired, and thus the probe displayed significant behavior with both the excitation wavelength and the dual-emission wavelengths located at NIR (650–900nm) region exclusively. Also, the probe showed excellent performance in high sensitivity and good selectivity towards HClO over other reactive oxygen species and a wide variety of coexist species in biological pH condition and had been successfully used to detect hypochlorous acid in serum samples and tap water samples.
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•A ratiometric fluorescent heptamethine cyanine-based probe for HClO was developed.•HClO was measured with the excitation and the dual-emission wavelengths at NIR Region.•The mechanism relies on HClO-promoted desulfurization to afford a guanidine group.•The probe showed high sensitivity and good selectivity towards HClO.
Although iron‐catalyzed cross‐coupling of Grignard reagents with alkyl halides has been well established, the adoption of the reaction for fluoroalkylations has not been reported because traditional ...catalytic systems often lead to defluorination reactions. Described herein is the investigation of an iron‐catalyzed cross‐coupling between arylmagnesium bromides and difluoroalkyl bromides with modified N,N,N′,N′‐tetramethyl‐ethane‐1,2‐diamine (TMEDA) as a ligand. The use of this bulky diamine, in which a butylene is substituted at one carbon atom of the ethylene backbone in TMEDA, enables the iron‐catalyzed difluoroalkylation under mild reaction conditions with a wide range of difluoroalkyl bromides, including vulnerable bromodifluoromethane, thus providing a general and cost‐efficient route for applications in medicinal chemistry.
Ligand design: An iron‐catalyzed cross‐coupling between arylmagnesium bromides and difluoroalkyl bromides, with modified N,N,N′,N′‐tetramethyl‐ethane‐1,2‐diamine (TMEDA) as a ligand, is described. The combination of iron(II) salts with L enables the difluoroalkylations with a wide range of difluoroalkyl bromides, thus providing general and cost‐efficient access to difluoroalkylated arenes that are of great interest in the life sciences.
A sustainable and green route to access diverse functionalized ketones via dehydrogenative–dehydrative cross‐coupling of primary and secondary alcohols is demonstrated. This borrowing hydrogen ...approach employing a pincer N‐heterocyclic carbene Mn complex displays high activity and selectivity. A variety of primary and secondary alcohols are well tolerant and result in satisfactory isolated yields. Mechanistic studies suggest that this reaction proceeds via a direct outer‐sphere mechanism and the dehydrogenation of the secondary alcohol substrates plays a vital role in the rate‐limiting step.
Borrowing hydrogen: A sustainable and green route to access diverse functionalized ketones via dehydrogenative–dehydrative cross‐coupling of primary and secondary alcohols is demonstrated. This borrowing‐hydrogen approach employing a pincer N‐heterocyclic carbene Mn complex displays high activity and selectivity. Mechanistic studies suggest that this reaction proceeds via a direct outer‐sphere mechanism and the dehydrogenation of the secondary alcohol substrates plays a vital role in the rate‐limiting step.
Oxidative stress is involved in the pathogenesis of vascular dementia. Studies have shown that lycopene can significantly inhibit oxidative stress; therefore, we hypothesized that lycopene can reduce ...the level of oxidative stress in vascular dementia. A vascular dementia model was established by permanent bilateral ligation of common carotid arteries. The dosage groups were treated with lycopene (50, 100 and 200 mg/kg) every other day for 2 months. Rats without bilateral carotid artery ligation were prepared as a sham group. To test the ability of learning and memory, the Morris water maze was used to detect the average escape latency and the change of search strategy. Hematoxylin-eosin staining was used to observe changes of hippocampal neurons. The levels of oxidative stress factors, superoxide dismutase and malondialdehyde, were measured in the hippocampus by biochemical detection. The levels of reactive oxygen species in the hippocampus were observed by dihydroethidium staining. The distribution and expression of oxidative stress related protein, neuron-restrictive silencer factor, in hippocampal neurons were detected by immunofluorescence histochemistry and western blot assays. After 2 months of drug administration, (1) in the model group, the average escape latency was longer than that of the sham group, and the proportion of straight and tend tactics was lower than that of the sham group, and the hippocampal neurons were irregularly arranged and the cytoplasm was hyperchromatic. (2) The levels of reactive oxygen species and malondialdehyde in the hippocampus of the model group rats were increased, and the activity of superoxide dismutase was decreased. (3) Lycopene (50, 100 and 200 mg/kg) intervention improved the above changes, and the lycopene 100 mg/kg group showed the most significant improvement effect. (4) Neuron-restrictive silencer factor expression in the hippocampus was lower in the sham group and the lycopene 100 mg/kg group than in the model group. (5) The above data indicate that lycopene 100 mg/kg could protect against the learning-memory ability impairment of vascular dementia rats. The protective mechanism was achieved by inhibiting oxidative stress in the hippocampus. The experiment was approved by the Animal Ethics Committee of Fujian Medical University, China (approval No. 2014-025) in June 2014.
A novel and practical fluoroalkyl radical-initiated cascade reaction was developed to access diverse 2-fluoroalkylbenzothiazoles by reacting various fluoroalkyl radical sources, including ...perfluoroalkyl iodide (IC n F2n+1, n = 3–8, 10), ICF(CF3)2, ICF2COOEt, ICF2CF2Cl, or ICF2CF2Br, tetramethylethane-1,2-diamine (TMEDA), and 2-isocyanoaryl thioethers in tetrahydrofuran under nitrogen atmosphere and blue-light irradiation conditions. Furthermore, this one-pot protocol could well be expanded to access various 2-fluoroalkylbenzoselenazoles starting from (2-isocyanophenyl)(methyl)selane, perfluoroalkyl iodides (IC n F2n+1, n = 3–8) or ICF2COOEt and TMEDA.
The introduction of phosphorus functional groups into the skeleton of thioflavones is an attractive task and of great significance. Herein, a metal‐free visible‐light‐induced radical cascade ...cyclization was developed for the preparation of 2‐phosphorylated thioflavones from methylthiolated alkynones and phosphine oxides. In water as a green reaction medium, a large number of such 2‐phosphorylated thioflavones were prepared, catalyzed by 4CzIPN 1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzene under visible‐light irradiation. These reactions could be performed at ambient temperature and feature simple operation, wide reaction scope, and recyclability of aqueous media.
Let there be light: By using water as a reaction medium, a large number of 2‐phosphorylated thioflavones are prepared through the reaction of methylthiolated alkynones and phosphine oxides catalyzed by 4CzIPN 1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzene under visible‐light irradiation.
A transition‐metal‐free visible‐light‐promoted radical phosphorylation/cyclization of N‐allylbenzamides with phosphine oxides for the synthesis of phosphoryl‐substituted dihydroisoquinolones was ...developed under room temperature. This protocol features mild reaction conditions, simple operation, broad substrate scope as well as scale‐up ability.
A Mn(III)‐mediated radical cyclization reaction of o‐vinylaryl isocyanides and arylboronic acids or diphenylphosphine oxides to access various 2‐functionalized quinolines under mild conditions was ...developed. With the introduction of radical stabilizing substituents (e. g. aryl and methyl group) on vinyl group, this reaction provides a regiospecific 6‐endo‐trig radical cyclization of o‐vinylaryl isocyanides, giving a number of structurally unique and biologically potential 2‐functionalized quinoline derivatives.
The palladium‐catalyzed difluoroalkylation of aryl boronic acids with bromodifluoromethylphosphonate, bromodifluoroacetate, and further derivatives has been developed. This method provides a facile ...and useful access to a series of functionalized difluoromethylated arenes (ArCF2PO(OEt)2, ArCF2CO2Et, and ArCF2CONR1R2) that have important applications in drug discovery and development. Preliminary mechanistic studies reveal that a single electron transfer (SET) pathway may be involved in the catalytic cycle.
Palladium does it: The palladium‐catalyzed difluoroalkylation of aryl boronic acids with bromodifluoromethylphosphonate, bromodifluoroacetate, and further derivatives has been developed (see scheme). Preliminary mechanistic studies reveal that a single electron transfer (SET) pathway may be involved in the catalytic cycle.
Precise genome editing via homology-directed repair (HDR) after double-stranded DNA (dsDNA) cleavage facilitates functional genomic research and holds promise for gene therapy. However, HDR ...efficiency remains low in some cell types, including some of great research and clinical interest, such as human induced pluripotent stem cells (iPSCs).
Here, we show that a double cut HDR donor, which is flanked by single guide RNA (sgRNA)-PAM sequences and is released after CRISPR/Cas9 cleavage, increases HDR efficiency by twofold to fivefold relative to circular plasmid donors at one genomic locus in 293 T cells and two distinct genomic loci in iPSCs. We find that a 600 bp homology in both arms leads to high-level genome knockin, with 97-100% of the donor insertion events being mediated by HDR. The combined use of CCND1, a cyclin that functions in G1/S transition, and nocodazole, a G2/M phase synchronizer, doubles HDR efficiency to up to 30% in iPSCs.
Taken together, these findings provide guidance for the design of HDR donor vectors and the selection of HDR-enhancing factors for applications in genome research and precision medicine.
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