ABSTRACT
Activatable probes with a higher signal-to-background ratio and accuracy are essential for monitoring liver cancer as well as intraoperative fluorescence navigation. However, the presence of only one biomarker is usually not sufficient to meet the high requirement of a signal-to-background ratio in cancer surveillance, leading to the risk of misdiagnosis. In this work, a dual-locked activation response probe, Si-NTR-LAP, for nitroreductase and leucine aminopeptidase was reported. This dual-locked probe provides better tumor recognition and a higher signal-to-noise ratio than that of single-locked probes (Si-LAP and Si-NTR). In both the subcutaneous tumor model and the more complex orthotopic hepatocellular carcinoma model, the probe was able to identify tumor tissue with high specificity and accurately differentiate the boundaries between tumor tissue and normal tissue. Therefore, the dual-locked probe may provide a new and practical strategy for applying to real patient tumor tissue samples.
Subject(s)
Leucyl Aminopeptidase , Liver Neoplasms , Nitroreductases , Liver Neoplasms/diagnosis , Liver Neoplasms/metabolism , Humans , Animals , Leucyl Aminopeptidase/metabolism , Leucyl Aminopeptidase/analysis , Nitroreductases/metabolism , Nitroreductases/analysis , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/metabolism , Mice , Fluorescent Dyes/chemistry , Optical ImagingABSTRACT
N 6-Methyladenosine (6mA) is a well-known prokaryotic DNA modification that has been shown to play epigenetic roles in eukaryotic DNA. Accurate detection and quantification of 6mA are prerequisites for molecular understanding of the impact of 6mA modification on DNA. However, the existing methods have several problems, such as high false-positive rate, time-consuming and complex operating procedures. Chemical sensors for the selective detection of 6mA modification are rarely reported in the literature. Fluorinated phenylboronic acid combined with 19F NMR analysis is an effective method for determining DNA or RNA modification. In this study, we presented a simple and fast chemical method for labelling the 6th imino group of 6mA using a boric-acid-derived probe. Besides, the trifluoromethyl group of trifluoromethyl phenylboronic acid (2a) could detect 6mA modification through 19F NMR. Combined with this sensor system, 6mA modification could be detected well and quickly in 6 types of deoxynucleoside mixtures and DNA samples. Taken together, the method developed in the current study has potential for specific detection of 6mA in biological samples.
Subject(s)
Adenosine/analogs & derivatives , Boronic Acids , DNA , DNA/chemistry , DNA Methylation , Magnetic Resonance SpectroscopyABSTRACT
Non-invasive dynamic tracking of lysosomes and their interactions with other organelles is important for the study of lysosomal function and related diseases. However, many fluorescent dyes developed so far to target lysosomes cannot be used to monitor these processes due to the high concentrations required for imaging, long cell penetration times, and non-ideal photostability. In this regard, we synthesized three lysosomal targeting probes with large Stokes shifts, good stability, and high brightness. The Q-P-ARh dye, developed by us for the first time, can stain lysosomes at ultra-low concentrations (1.0â nM) without affecting the physiological functions of the lysosomes. More importantly, its excellent anti-interference ability and ultrafast lysosomal staining ability (within 1.0â min) clearly monitored the entire dynamic process of lipophagy. Ultimately, this method can greatly contribute to the study of autophagy pathways. This novel fluorescence platform shows great promise for the development of biological probes for application in pathological environments.
Subject(s)
Autophagy , Fluorescence , Fluorescent Dyes/chemistry , Optical Imaging , Fluorescent Dyes/chemical synthesis , Hep G2 Cells , Humans , Lysosomes/chemistryABSTRACT
A computer-generated hologram (CGH) is the core component for an aspheric surface test. According to fabrication demands, it is necessary to convert the designed CGH phase compensation function into the processed pattern, that is, the fringe discretization process. In this paper, we propose a new discretization method for a CGH in a test of the freeform surface, and realized the encoding of processed fringes by MATLAB software. Furthermore, we designed the experiment to verify the accuracy of the new discretization method and compared the calculation efficiency between the new algorithm and the reported algorithm. Finally, based on the testing requirement of a freeform mirror in a camera optical system, we completed the design, encoding, and fabrication of the CGH sample, and analyzed the influence of various errors on wavefront accuracy of the CGH.
ABSTRACT
An iodine-mediated synthesis of 3-acylbenzothiadizine 1,1-dioxides is described. A range of electronically diverse acetophenones reacted well with several 2-aminobenzenesulfonamides, affording 3-acylbenzothiadiazine 1,1-dioxides in good yields.
ABSTRACT
An efficient method to synthesize substituted quinolines from ketones and 2-amino benzylamines is described. Copper-catalyzed C-N cleavage of amines followed by condensation with ketones deliver quinolines in moderate to high yields. The broad scope of substrates and the use of air as the sole oxidant make this transformation very attractive.
Subject(s)
Carbon/chemistry , Copper/chemistry , Nitrogen/chemistry , Quinolines/chemistry , Quinolines/chemical synthesis , Benzylamines/chemistry , Catalysis , Chemistry Techniques, SyntheticABSTRACT
An efficient method for the oxidative amidation of benzylic aldehydes or alcohols with ammonium salts has been developed for the synthesis of primary amides using Et4NI as the catalyst and tert-butyl hydroperoxide as the oxidant. This amidation reaction is operationally straightforward and provides primary amides in moderate to good yields under mild conditions.
Subject(s)
Alcohols/chemistry , Aldehydes/chemistry , Amides/chemical synthesis , Ammonium Compounds/chemistry , Tetraethylammonium/chemistry , Amides/chemistry , Catalysis , Molecular Structure , Salts/chemistryABSTRACT
The fluorescence high-throughput screening method is of importance for new antioxidant drug candidate discovery for the treatment of serious hepatorenal syndrome, which displayed an obvious upregulated peroxynitrite level. However, most of the current ONOO- probes possessed incomplete fluorescence quenching efficiency, which can result in non-negligible probe inherent fluorescence. Hence, we utilized the probe conjugated structure disruption strategy to construct hydrogenation phosphorus-substituted rhodamine (H-PRh) with "zero" probe inherent fluorescence character. Based on the precursor, a series of natural products were screened for identifying antioxidant drug candidates. Luteolin was screened out by activating the Sirt1-Nrf2-HO-1 signaling pathway to regulate the accumulation of ONOO- in the hepatorenal syndrome. Overall, the "zero" probe inherent fluorescence ONOO- sensor constructed here applies for a promising and versatile toolbox for illuminating the ONOO--related pathological process in the hepatorenal syndrome. Besides, this strategy of constructing highly sensitive sensors could serve as a valuable reference for further fluorescent probes.
Subject(s)
Antioxidants , Fluorescent Dyes , High-Throughput Screening Assays , Peroxynitrous Acid , Peroxynitrous Acid/analysis , Antioxidants/chemistry , Antioxidants/pharmacology , Humans , High-Throughput Screening Assays/methods , Fluorescent Dyes/chemistry , NF-E2-Related Factor 2/metabolism , Biological Products/chemistry , Biological Products/pharmacology , Animals , Sirtuin 1/metabolism , Heme Oxygenase-1/metabolism , Rhodamines/chemistry , Luteolin/chemistry , Luteolin/pharmacology , Fluorescence , Signal Transduction/drug effectsABSTRACT
High-performance fluorescent probes stand as indispensable tools in fluorescence-guided imaging, and are crucial for precise delineation of focal tissue while minimizing unnecessary removal of healthy tissue. Herein, machine-learning-assisted strategy to investigate the current available xanthene dyes is first proposed, and a quantitative prediction model to guide the rational synthesis of novel fluorescent molecules with the desired pH responsivity is constructed. Two novel Siârhodamine derivatives are successfully achieved and the cathepsin/pH sequentially activated probe Siârhodamineâcathepsin-pH (SiRâCTS-pH) is constructed. The results reveal that SiRâCTS-pH exhibits higher signal-to-noise ratio of fluorescence imaging, compared to single pH or cathepsin-activated probe. Moreover, SiRâCTS-pH shows strong differentiation abilities for tumor cells and tissues and accurately discriminates the complex hepatocellular carcinoma tissues from normal ones, indicating its significant application potential in clinical practice. Therefore, the continuous development of xanthene dyes and the rational design of superior fluorescent molecules through machine-learning-assisted model broaden the path and provide more advanced methods to researchers.
Subject(s)
Cathepsins , Fluorescent Dyes , Machine Learning , Rhodamines , Rhodamines/chemistry , Fluorescent Dyes/chemistry , Humans , Hydrogen-Ion Concentration , Cathepsins/metabolism , Silicon/chemistry , Optical Imaging/methods , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/diagnostic imagingABSTRACT
An efficient, concise, and transition metal-free synthesis of functionalized sulfonylated five-membered heterocyclic compounds via an S(N)Ar reaction has been developed. Using commercially available sodium sulfinates as sulfonylation reagents, various five-membered heterocyclic sulfones were obtained in good yields.
Subject(s)
Heterocyclic Compounds/chemistry , Sulfhydryl Compounds/chemical synthesis , Crystallography, X-Ray , Models, Molecular , Molecular Structure , Sulfhydryl Compounds/chemistryABSTRACT
Accurate detection of target analytes and generation of high-fidelity fluorescence signals are particularly critical in life sciences and clinical diagnostics. However, the majority of current NIR-I fluorescent probes are vulnerable to pH effects resulting in signal distortion. In this work, a series of fluorescence-tunable and pH-independent probes are reported by combining optically tunable groups of unsymmetric Si-rhodamines and introducing the methoxy instead of the spiro ring on the benzene ring at position 9. To validate the concept, the leucine aminopeptidase response site was introduced into Si-2,6OMe-NH2 with the best optical properties to synthesize Si-LAP for monitoring the intrahepatic LAP in vivo. Therefore, the design approach may provide a new and practical strategy for designing innovative functional fluorescent probes and generating high-stability and high-fidelity fluorescent signals.
Subject(s)
Fluorescent Dyes , Leucyl Aminopeptidase , Fluorescent Dyes/chemistry , Rhodamines/chemistry , Fluorescence , Hydrogen-Ion ConcentrationABSTRACT
An "AND" logic gate-based NIR fluorescent probe Si-NH2-Glu was developed based on novel meso-amine Si-Rhodamine, which combined γ-glutamyl transpeptidase and pH dual-responsive sites. The features of Si-NH2-Glu enable it to be applied in orthotopic tumor imaging and fluorescence-guided surgery.
Subject(s)
Breast Neoplasms , Fluorescent Dyes , Humans , Female , gamma-Glutamyltransferase , Optical Imaging/methods , Hydrogen-Ion ConcentrationABSTRACT
Enriching the palette of high-performance fluorescent dyes is vital to support the frontier of biomedical imaging. Although various rhodamine skeletons remain the premier type of small-molecule fluorophores due to the apparent high brightness and flexible modifiability, they still suffer from the inherent defect of small Stokes shift due to the nonideal fluorescence imaging signal-to-background ratio. Especially, the rising class of fluorescent dyes, sulfone-substituted xanthone, exhibits great potential, but low chemical stability is also pointed out as the problem. Molecular engineering of sulfone-xanthone to obtain a large Stokes shift and high stability is highly desired, but it is still scarce. Herein, we present the combination modification method for optimizing the performance of sulfone-xanthone. These redesigned fluorescent skeletons owned greatly improved stability and Stokes shift compared with the parent sulfone-rhodamine. To the proof of bioimaging capacity, annexin protein-targeted peptide LS301 was introduced to the most promising dyes, J-S-ARh, to form the tumor-targeted fluorescent probe, J-S-LS301. The resulting probe, J-S-LS301, can be an outstanding fluorescence tool for the orthotopic transplantation tumor model of hepatocellular carcinoma imaging and on-site pathological analysis. In summary, the combination method could serve as a basis for rational optimization of sulfone-xanthone. Overall, the chemistry reported here broadens the scope of accessible sulfone-xanthone functionality and, in turn, enables to facilitate the translation of biomedical research toward the clinical domain.
ABSTRACT
A novel and simple transition metal-free direct arylation of arene and N-heteroarenes with diaryliodonium salts has been developed. This cross-coupling reaction is promoted only by base and gives the desired products in moderate to good yields.
ABSTRACT
The introduction of amines onto aromatics without metal catalysts and chemical oxidants is synthetically challenging. Herein, we report the first example of an electrochemical cross-dehydrogenative aromatization (ECDA) reaction of saturated cyclohexanones and amines to construct anilines without additional metal catalysts and chemical oxidants. This reaction exhibits a broad scope of cyclohexanones including heterocyclic ketones, affording a variety of aromatic amines with various functionalities, and shows great potential in the synthesis of biologically active compounds.
ABSTRACT
Different chemical states of nitrogen are present in many freshwater and marine ecosystems, and nitrite ions are one of the most toxic water-soluble nitrogen species. Developing an effective and convenient sensing method to constantly detect the concentration of nitrite has become a wide concern. Here, a novel near-infrared fluorescent probe (AAC) was designed and synthesized via the "covalent assembly" principle, showing excellent selectivity and high sensitivity for nitrite. A new nitrite-quantitative method was established with the help of AAC, and the detection limit of nitrite using the new method was as low as 6.7 nM. AAC was successfully applied for the quantitative detection of nitrite in real-world environmental and food samples (including river water and Chinese sauerkraut), and the detection results were essentially identical to the results obtained from the traditional Griess assay. Moreover, AAC was successfully applied for tracking nitrite in Escherichia coli by fluorescence imaging. Since nitrite can have devastating effects, the method established with AAC allowed us to "see" effectively about the water quality, food quality, etc.
Subject(s)
Fluorescent Dyes/chemistry , Nitrites/analysis , Spectroscopy, Near-Infrared/methods , Coumarins/chemistry , Escherichia coli/chemistry , Fresh Water/analysis , Limit of DetectionABSTRACT
An optically active BINOL-terpyridine based Cu(II) complex (R)-2 was prepared. Sonication of (R)-2 in CHCl(3) led to the formation of a stable gel. The interaction of this gel with chiral amino alcohols was studied. It was found that (S)-phenylglycinol (0.10 equiv) could break the gel network of (R)-2 (3.75% w/v, g/mL) in CHCl(3) to cause gel collapsing but (R)-phenylglycinol (0.10 equiv) could not. Similar enantioselective gel collapsing was also observed with (R)- and (S)-1-amino-2-propanol. This study demonstrates that chiral molecular gels are potentially useful for visual chiral discrimination. Complex (R)-2 in solution also exhibited significant enantioselective fluorescent enhancement in the presence of a variety of amino alcohols.
ABSTRACT
A highly reactive ylide tBuA was introduced, which could react rapidly with the 5-formyl and 4-amino groups of 5-formylcytosine (5fC) under mild conditions without any co-solvent or catalyst in a manner of Wittig olefination and intramolecular nucleophilic substitution to yield a cyclized fluorescent adduct, which meets the demands of both single-base resolution sequencing and fluorescence switch-on detection of 5fC in DNA.
Subject(s)
Cytosine/analogs & derivatives , DNA/chemistry , Fluorescent Dyes/chemistry , Cytosine/analysis , Density Functional Theory , Molecular Structure , Water/chemistryABSTRACT
A novel and efficient method to synthesize rigid bis-coumarins based on the dimerization of coumarinyl aldehydes was developed. This procedure is additive- and column-free, providing a facile and environment-friendly way to prepare fluorophores. The prepared novel fluorescent bis-coumarins exhibit favorable photophysical properties with good sensitivity and selectivity towards G-quadruplexes (G4s).
ABSTRACT
Inspired by the natural properties of the phospholipid bilayer (PB), three probes that could assemble with phospholipid bilayer through hydrophobic and electrostatic interactions are reported for rapid and accurate specific imaging of plasma membrane in 2D and 3D cell models. What's more, we have captured the picture of probe assembly with the phospholipid bilayer in cells for the first time.