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CuAAC
DYES AND PIGMENTS · 2021 · IF 4.889

A click-induced fluorescence-quenching sensor based on gold nanoparticles for detection of copper(Ⅱ) ion and ascorbic acid

Shijun Lin,Shuwen Liu,Guofei Dai,Xiaojin Zhang,Fan Xia,Yu Dai

Gold nanoparticles (AuNPs), as one of the major tools of fluorescence-quenching sensors, have been widely used in biochemical analysis through fluorescence resonance energy transfer (FRET) effect. With the development of chemistry and biochemistry, reaction-based fluorescent sensors have attracted increasing attention because of their unique selectivity, high sensitivity and rapid detection. Here we report a click-induced fluorescence-quenching sensor based on AuNPs for detection of copper ion (Cu 2+ ) and ascorbic acid (AA). A fluorescent dye Rhodamine B-(CH 2 CH 2 O) 4 -azide (RB-PEG 4 -N 3 ) is conjugated to the surface of AuNPs via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) in the presence of Cu 2+ and AA, leading to the fluorescence quenching of Rhodamine B. The sensor responds quickly (within less than 3 min). The fluorescent intensity linearly correlates with the concentration of Cu 2+ in the range of 0–108 μM. The limit of detection (LOD) for Cu 2+ is 5.8 μM. The concentration range for detection of AA is 0–3 mM. The LOD for AA is 0.13 mM. In addition, the application of the sensor is verified by performing detection in real samples such as fresh orange, juice, VC tablet, and lake water. This work expands the application of AuNPs-based fluorescence-quenching sensors for multi-component detection.

研究领域: 化学 · 生物化学 · 纳米技术 · 分析化学
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MICROCHEMICAL JOURNAL · 2024 · IF 4.9

Click chemistry-mediated stable isotope labeling combined with HPLC-MS/MS analysis for highly sensitive determination of steroid hormones

Xiao-Kang Fu,Si-Qi Han,Xiao-Bo Zhao,Jing-Yan Kang,Wei Ha,Yan-Ping Shi

Steroid hormone residues in food are a significant sources of endocrine disrupting chemicals (EDCs) that can adversely affect public health. However, the current analytical methods for determining steroid hormones using liquid chromatography-tandem mass spectrometry (LC-MS/MS) can be challenging due to the poor ionization efficiency of steroid hormones and the matrix effect of complex food samples. Herein, based on Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and stable isotope labeling (SIL) technique, a novel pair of chemoselective probes ABI / d 5 -ABI was precisely designed and synthesized. This pair of probes comprises a H/D isotope tag, a linker, a reactive site azido group (N 3 ) and a MS tag (imidazolium salt). The probe ABI was employed to label ethynyl-containing steroid hormones in real samples and d 5 -ABI was applied to label standards, respectively, followed by mixing the two labeled samples for high performance (HP)LC-MS/MS analysis. It was found that the ionization efficiencies of target analytes were increased by 17–4532 folds after ABI labeling. More importantly, the heavy labeled samples serving as internal standards (ISs) can effectively compensate matrix effect during HPLC-MS/MS analysis. Finally, the proposed SIL-HPLC-MS/MS method was successfully used to highly sensitive determine four synthetic steroid hormones in food samples (milk, pork and egg). Furthermore, the good detection limits (0.015–0.020 ng/mL), satisfactory recoveries (75.7–122.9 %), and precisions (RSDs less than 9.2 %) were obtained. Hence, the established method not only provides new insights in designing SIL probes for determination of ethynyl-containing analytes within complex matrix, but also extends the application of CuAAC reaction in the field of food chemistry.

研究领域: 分析化学 · 食品科学 · 质谱技术
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CHEMICAL ENGINEERING JOURNAL · 2022 · IF 16.744

In-situ activation of CuAl-LDH nanosheets to catalyze bioorthogonal chemistry in vivo in tumor microenvironment for precise chemotherapy and chemodynamic therapy

Sa Wang,Shuqing Yang,Zhuolin Cui,Xueyan Liu,Yu Yang,Tao Wang,Wenjuan Ma,Yubin Zhou,Ruizheng Liang,Dan Yan,Huizhi Chen

Precise activation of therapeutic molecules in tumor tissues is the key step to ensure targeted antitumor performance and reduce adverse effects towards normal tissues and organs. Although the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), i.e., bioorthogonal chemistry, has been used for the rapid synthesis of anticancer drugs in cells, it remains a great challenge to realize precise in vivo drug synthesis in tumor sites for precise cancer treatment. In this work, we first report the in-situ activation of CuAl-layered double hydroxide (CuAl-LDH) nanosheets to realize Cu(I)-catalyzed bioorthogonal chemistry in vivo in tumor microenvironment (TME) for precise chemotherapy and chemodynamic therapy (CDT). The Cu(II) ions in the biocompatible CuAl-LDH nanosheets can be in-situ reduced to Cu(I) ions partially by the overexpressed glutathione in TME. The generated Cu(I) can serve as a catalyst to catalyze the CuAAC reaction between alkyne and azide in TME, thus realizing in vivo drug synthesis for precise chemotherapy. Meanwhile, the generated Cu(I) can catalyze the Fenton-like reaction to generate toxic hydroxyl radicals (⋅OH) from H 2 O 2 in TME for CDT. Therefore, CuAl-LDHs can be used for the targeted synergistic chemotherapy and CDT to achieve highly precise and efficient elimination of cancer cells in vitro and inhibition of tumors in vivo .

研究领域: 纳米技术 · 癌症治疗 · 生物化学 · 材料科学
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ANALYTICAL CHEMISTRY · 2021 · IF 6.986

Bioinspired Artificial “Clickase” for the Catalytic Click Immunoassay of Foodborne Pathogens

Xianlong Zhang,Yongning Wu,Juhong Chen,Yan Yang,Guoliang Li

The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click reaction has drawn increasing attention in the field of analytical science. However, the poor stability of Cu(I) usually hinders not only the simplicity of the click reaction but also its applications in precise analyses. Therefore, the development of a nanocatalyst containing stable Cu(I) is of great significance for broadening the application of CuAAC-based assays. Herein, inspired by the active center structure of natural multicopper oxidases (MCOs), we successfully prepared a novel nanocatalyst containing abundant stable Cu(I) as an artificial “clickase” (namely, CCN) by using glutathione to stabilize Cu(I). The stability and enzyme-like catalytic activity in the CuAAC reaction of the prepared CCN clickase were studied, and the catalytic mechanism of the CCN clickase-mediated CuAAC reaction between 3-azide-7-hydroxycoumarin (Azide 1) and propargyl alcohol (Alkyne 2) was also revealed. Compared with the existing solid CuO nanocatalysts used in CuAAC-based assays, CCN clickases exhibited plenty of superior properties (including high stability, excellent catalytic activity, no requirements of dissolution and reducing agents/radical initiator during the detection, well-defined porosities benefiting the substrate diffusion, and good biocompatibility), which can greatly increase the reaction efficiency and shorten the detection time. Encouraged by these remarkable performances, CCN clickases were used as labels to establish a new catalytic click fluorescence immunoassay for foodborne pathogens. Notably, the proposed CCN clickase-based immunoassay exhibited high analytical performances for the quantification of Salmonella enteritidis in the linear range of 102–106 CFU/mL with a limit of detection as low as 11 CFU/mL. The developed method has also been used in the determination of S. enteritidis in food samples, showing its great potential in the detection of foodborne pathogens.

研究领域: 分析化学 · 纳米技术 · 免疫学 · 食品安全
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EUROPEAN POLYMER JOURNAL · 2013 · IF 2.562

Multiresponsive supramolecular gels constructed by orthogonal metal–ligand coordination and hydrogen bonding

Wengui Weng,Xiuli Fang,Huan Zhang,Huiying Peng,Yangju Lin,Yinjun Chen

Macromonomers bearing tridentate 2,6-bis(1,2,3-trizol-4-yl)pyridine (BTP) ligand unit synthesized via CuAAC “click” chemistry in the middle of the chain and two ureidopyrimidinone (UPy) motifs on the ends linked to the central BTP unit via PEGs of various lengths were synthesized and used for the study of gelation both with and without the presence of Eu(III) ions. Various interesting gelation behaviors were found. Gels exhibited various multi-responsive properties, including photoluminescence, mechanoresponsive properties, self-healing abilities, thermorepsonsive properties and chemoresponsive properties. The different gelation abilities and multi-responsive properties for different systems were shown to be resulted from difference in PEG linker lengths and the introduction of orthogonal metal–ligand coordination and hydrogen bonding interactions. The selective responsiveness to different chemicals would allow the development of modular sensory systems that utilize a combination of orthogonal supramolecular interactions.

研究领域: 超分子化学 · 材料科学 · 高分子化学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

A Clickase-Mediated Immunoassay Based on Nanopore and Bionic Signal Labels for Ultrasensitive, Portable, and On-Site Detection of Ricin

Jianing Chen,Zhuoqun Su,Wenrui Li,Ziye Pei,Di Wu,Lin Li,Yongning Wu,Guoliang Li

It is of particular importance to develop an effective method that possesses several merits simultaneously of rapid, ultrasensitive, portable, and on-site detection potential for food safety detection. Herein, we propose a clickase-mediated immunoassay based on nanopore and bionic signal labels for the detection of ricin. The introduction of Cu/Cys clickase and nanopore simultaneously effectively addressed the inherent limitations of natural enzymes and colorimetric signal output, respectively. Using this method, bionic signal labels can be easily formed through DNA and Gram-positive bacterial cell wall terminal peptide fragments (labeled by alkynyl and azide, respectively) and vancomycin. Translocation of the D-P@vancomycin through the nanopore generated highly specific oscillation current traces. This method showed a great on-site detection potential and superior analytical performance owing to the combination of the specificity of antibodies, high CuAAC click reaction catalytic efficiency of clickase, ultrasensitivity of the nanopore, and high signal resolution of D-P@vancomycin. Moreover, the practical applicability of the established method was also verified, achieving a limit of detection (LOD) down to 200.9 ag/mL with a wide linear relationship under the optimized conditions. In conclusion, this method is promising for rapid, portable, ultrasensitive, and on-site food safety detection.

研究领域: 分析化学 · 纳米技术 · 食品安全 · 生物传感器 · 免疫测定
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FOOD CHEMISTRY · 2022 · IF 9.231

Ultrasensitive microfluidic immunosensor with stir bar enrichment for point-of-care test of Staphylococcus aureus in foods triggered by DNAzyme-assisted click reaction

Jiaqi Wang,Lei Tan,Wenchao Bi,Haoyu Shen,Dengfeng Li,Zhenzhong Yu,Ning Gan

This work demonstrated an ultrasensitive and simple microfluidic immunosensor for point-of-care test of Staphylococcus aureus ( S. aureus ) based on the stir bar enrichment and DNAzyme-assisted click reaction. Initially, S. aureus was enriched by the 4-mercaptophenylboronic acid-functionalized stir bar. The yolk antibody (immunoglobulin Y) and copper-labeled polydopamine nanoparticles were then specifically conjugated with the captured target. The Cu(II) was released under acidic conditions and effectively catalyzed the copper-catalyzed azide-alkyne cycloaddition (CuAAC) between the alkyne group-labeled DNAzyme and the streptavidin–biotin-azido with the assistance of DNAzyme. Finally, the DNAzyme-streptavidin complexes were detected by microfluidic chips to quantify S. aureus . Under optimum conditions, this immunosensor showed good detection performances toward S. aureus within 10 to 2.5 × 10 4 CFU/mL with a limit of detection of 3 CFU/mL. Moreover, the satisfying detection results of real samples of animal origin also implied that this immunosensor owned great potential in practical applications.

CAS / MDL: 111-30-8 1633-78-9
研究领域: 生物技术 · 分析化学 · 食品安全 · 即时诊断 · 微流控技术
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JOURNAL OF POLYMER SCIENCE · 2022 ·Vol. 60 ·期 13 ·1954-1961 · IF 3.046

Preparation of α,ω-heterobifunctionalized poly(N-vinylpyrrolidone) via a bis-clickable RAFT reagent

Jingrui Liu,Wei Sun,Zhaoqiang Wu,Hong Chen

A novel trithiocarbonate reversible addition−fragmentation chain transfer (RAFT) reagent, 3-azidopropyl (4-[fluorosulfonyl]benzyl)trithiocarbonate (Az-FSBCT), which has both clickable azidopropyl and sulfonyl fluoride moieties, was designed and synthesized. Using the RAFT agent Az-FSBCT and triethylboron as an initiator, well-defined poly( N -vinylpyrrolidone) (PVP), in which the azide and sulfonyl fluoride groups are at the α and ω positions of the polymer chains, were prepared without prior deoxygenation at room temperature. Moreover, the possibilities for the construction of new functionalized polymers were also demonstrated by a “click” copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) and sulfur(VI)-fluoride exchange (SuFEx) postreaction using these terminal functional PVPs. Graphical

研究领域: 高分子化学 · 材料科学 · 有机化学
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JOURNAL OF INORGANIC BIOCHEMISTRY · 2022 · IF 4.336

Unlocking the potential of iridium and ruthenium arene complexes as anti-tumor and anti-metastasis chemotherapeutic agents

Mengdi Lv,Xiaoting Qian,Shijie Li,Jie Gong,Qun Wang,Yong Qian,Zhi Su,Xuling Xue,Hong-Ke Liu

It is a major challenge to design novel multifunctional metal-based chemotherapeutic agents for anti-tumor and anti-metastasis applications. Two complexes ( OA-Ir and OA-Ru ) were synthesized via CuAAC (copper-catalyzed azide-alkyne cycloaddition) reaction from nontoxic Ir - N 3 or Ru - N 3 species and low toxic alkynyl precursor OA-Alkyne, and exhibited satisfactory anti-tumor and anti-metastasis pharmacological effects . Conjugation of Oleanolic acid (OA) and metal-arene species significantly enhanced the cytotoxicity in A2780 cells compared to the precursors through mitochondrial-induced autophagy pathway. Moreover, the two complexes could inhibit the cell metastasis and invasion through damage of actin dynamics and down-regulation of MMP2/MMP9 proteins. Combination of two precursors improved the lipophilicity and biocompatibility, simultaneously enhanced the cell uptake and the mitochondrial accumulation of metal-arene complexes, which caused mitochondrial membrane potential damage, oxidative phosphorylation , ATP depletion and autophagy. Besides, OA-Ir and OA-Ru displayed excellent activity to disintegrate the 3D multicellular tumor spheroids , showing potential for the treatment of solid tumors. This work provides a new way for developing novel metal-based complexes via CuAAC reaction for simultaneously inhibiting tumor proliferation and metastasis.

研究领域: 化学 · 药理学 · 癌症研究 · 材料科学
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BIOMATERIALS · 2020 · IF 10.317

Fusion peptide engineered “statically-versatile” titanium implant simultaneously enhancing anti-infection, vascularization and osseointegration

Junjian Chen,Guansong Hu,Tianjie Li,Yunhua Chen,Meng Gao,Qingtao Li,Lijing Hao,Yongguang Jia,Lin Wang,Yingjun Wang

Although antimicrobial titanium implants can prevent biomaterial-associated infection (BAI) in orthopedics, they display cytotoxicity and delayed osseointegration . Therefore, versatile implants are desirable for simultaneously inhibiting BAI and promoting osseointegration, especially “statically-versatile” ones with nonessential external stimulations for facilitating applications. Herein, we develop a “statically-versatile” titanium implant by immobilizing an innovative fusion peptide (FP) containing HHC36 antimicrobial sequence and QK angiogenic sequence via sodium borohydride reduction promoted Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC-SB), which shows higher immobilization efficiency than traditional CuAAC with sodium ascorbate reduction (CuAAC-SA). The FP-engineered implant exhibits over 96.8% antimicrobial activity against four types of clinical bacteria ( S. aureus , E. coli , P. aeruginosa and methicillin-resistant S. aureus ), being stronger than that modified with mixed peptides. This can be mechanistically attributed to the larger bacterial accessible surface area of HHC36 sequence. Notably, the implant can simultaneously enhance cellular proliferation , up-regulate expressions of angiogenesis-related genes/proteins (VEGF and VEGFR-2) of HUVECs and osteogenesis-related genes/proteins (ALP, COL-1, RUNX-2, OPN and OCN) of hBMSCs . In vivo assay with infection and non-infection bone-defect model reveals that the FP-engineered implant can kill 99.63% of S. aureus , and simultaneously promote vascularization and osseointegration. It is believed that this study presents an excellent strategy for developing “statically-versatile” orthopedic implants .

CAS / MDL: 7787-70-4
研究领域: 骨科 · 材料科学 · 生物材料 · 组织工程 · 生物医学工程
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