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Advanced probes for imaging viscous lipids microenvironment in vitro and in vivo are desirable for the study of membranous organelles and lipids traffic. Herein, a reaction-based dihydroquinoline probe (DCQ) was prepared via linking a diethylamino coumarin fluorophore with a N-methylquinoline moiety. DCQ is stable in low viscous aqueous mediums and exhibits green fluorescence, which undergoes fast autoxidation in high viscous mediums to form a fluorescent product with deep-red to near-infrared (NIR) emission, rendering the ability for dual-color imaging. Living cell imaging indicated that DCQ can effectively stain lysosomal membranes with deep-red fluorescence. Super-resolution imaging of lysosome vesicles has been achieved by DCQ and stimulated emission depletion (STED) microscopy. In addition, DCQ realizes multiple organs imaging in zebrafish, whose dual-color emission can perfectly discriminate zebrafish's yolk sac, digestive tract and gallbladder. Most importantly, DCQ has been successfully used to establish a gallbladder-visualizable zebrafish model for the evaluation of drug stress.

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Fluorescence-guided surgery (FSG) is a surgical method to selectively visualize the tumor site using fluorescent materials with instrumental setups in the operation rooms. It has been widely used in the surgery of brain tumors, such as glioblastoma (GBM), which is difficult to distinguish from normal tissue. Although FSG is crucial for GBM surgery, the commercially available fluorescent materials for FSG have shown serious adverse effects. To satisfy the clinical demand, we recently reported reaction-based fluorescent probes based on a 4-chloro-7-nitrobenzofurazan (NBD) fluorophore that can detect cysteine (Cys) and homocysteine (Hcy), a biomarker of GBM, and their applications for the GBM diagnosis and FSG. However, our probes have cellular toxicity issues arising from the leaving group (LG) that is generated after the reaction of the fluorescent probe and the analytes. In this study, we disclosed a nontoxic fluorescent probe for sensing biothiols and their clinical applications for real-time human glioblastoma visualization. Systematic toxicity analysis of several LGs was conducted on several cell lines. Among the LGs, 2-hydroxy-pyridine showed negligible toxicity, and its fluorescent probe derivative (named NPO-o-Pyr) showed high specificity and sensitivity (LOD: 0.071 ppm for Cys; 0.189 ppm for Hcy), a fast response time (<5 min) to Cys and Hcy, and high biocompatibility. In addition, NPO-o-Pyr can significantly detect the GBM site both in actual clinical samples as well as in the GBM-xenografted mouse model. We are confident that NPO-o-Pyr will become a new substitute in FSG due to its capability to overcome the limitations of the current fluorescent probes.

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Hydrogen peroxide (H2O2) is a type of reactive oxygen species that regulates essential biological processes. Despite the central role of H2O2 in pathophysiological states, available molecular probes for assessing H2O2 in vivo are still limited. This work develops hyperpolarized 15N-boronobenzyl-4-cyanopyridinium (15N-BBCP) as a rationally designed molecular probe for detecting H2O2. The 15N-BBCP demonstrated favorable physicochemical and biochemical properties for H2O2 detection and dynamic nuclear polarization, allowing noninvasive detection of H2O2. In particular, 15N-BBCP and the products possessed long spin-lattice relaxation times and spectrally resolvable 15N chemical shift differences. The performance of hyperpolarized 15N-BBCP was demonstrated both in vitro and in vivo with time-resolved 15N-MRS. This study highlights a promising approach to designing a reaction-based 15N-labeled molecular imaging agent for detecting oxidative stress in vivo.

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A latent turn-on fluorescent probe for the detection of malononitrile (NCCH2CN), a precursor of hydrogen cyanide (HCN) in the mammalian tissue metabolism, is developed based on reaction-based fluorophore generation for the first time. Malononitrile is utilized within a wide spectrum of academic and industrial applications, and it is a key reagent to make o-chlorobenzylidene malononitrile (CS gas; tear gas), which is used for riot control. Due to its extensive use as well as potential health risks and the environmental pollution, malononitrile monitoring method has been required. In this paper, we discovered that our key sensing platform, 6-(dimethylamino)-3-hydroxy-2-naphthaldehyde (named Mal-P1), responds sensitively and selectively towards malononitrile. The Knoevenagel condensation induced benzo [g]coumarin formation of Mal-P1 with malononitrile showed significant fluorescence turn-on response. In addition, Mal-P1 showed the malononitrile sensing ability in environmental samples (real water, CS gas) and imaging ability in biological sample (HeLa cell line) using fluorescence microscopy with low cytotoxicity. The successful demonstrations will facilitate further applications in a variety of fields.

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Diethylcyanophosphonate (DCNP) is a simulant of Tabun (GA) which is an extremely toxic chemical substance and is used as a chemical warfare (CW) nerve agent. Due to its toxic properties, monitoring methods have been constantly come under the spotlight. What we are proposing within this report is a next-generation fluorescent probe, DMHN1, which allows DCNP to become fully traceable in a sensitive, selective, and responsive manner. This is the first fluorescent turn-on probe within the dipolar naphthalene platform induced by ESIPT (excited state intramolecular proton transfer) suppression that allows us to sense DCNP without any disturbance by other similar G-series chemical weapons. The successful demonstrations of practical applications, such as in vitro analysis, soil analysis, and the development of an on-site real-time prototype sensing kit, encourage further applications in a variety of fields.

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We designed and synthesized a new series of intramolecular charge transfer (ICT) molecules (compounds T1, T2 and T3) by attaching various electron-donating thiophene groups to the triphenylamine backbone with aldehyde group as the electron acceptor. Based on the nucleophilic addition reaction between hydrogen sulfite and aldehyde, all compounds could act as ratiometric optical probe for hydrogen sulfite and displayed efficient chromogenic and fluorogenic signaling. Upon the addition of hydrogen sulfite anions, probe T3 displayed apparent fluorescent color changes from yellowish-green to blue, with a large emission wavelength shift (Δλ = 120 nm). T3 responded to hydrogen sulfite with high sensitivity and the detection limit was determined to be as low as 0.9 µM. At the same time, apparent changes in UV-vis spectra could also be observed. By virtue of the special nucleophilic addition reaction with aldehyde, T3 displayed high selectivity over other anions. Copyright © 2016 John Wiley & Sons, Ltd.

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Most of the near-infrared (NIR) fluorescent copper ion probes are coordination-based, and the fluorescence enhancement is between 10 and 20 folds. Herein, a novel NIR fluorescent dye named CSCN with excellent photostability and a reaction-based Cu(2+) NIR probe named CSCN-Cu were reported. CSCN exhibited good photostability toward photo irradiation. CSCN-Cu showed lower background fluorescent interference and over 40-fold fluorescence enhancement in NIR region, it also exhibited good selectivity toward Cu(2+) in Hepes solution. Biotic experiments demonstrated that CSCN-Cu possessed low toxicity and successfully imaged Cu(2+) in living cells under the conditions performed.

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Chelatable, mobile forms of divalent zinc, Zn(II), play essential signaling roles in mammalian biology. A complex network of zinc import and transport proteins has evolved to control zinc concentration and distribution on a subcellular level. Understanding the action of mobile zinc requires tools that can detect changes in Zn(II) concentrations at discrete cellular locales. We present here a zinc-responsive, reaction-based, targetable probe based on the diacetyled form of Zinpyr-1. The compound, (6-amidoethyl)triphenylphosphonium Zinpyr-1 diacetate (DA-ZP1-TPP), is essentially nonfluorescent in the metal-free state; however, exposure to Zn(II) triggers metal-mediated hydrolysis of the acetyl groups to afford a large, rapid, and zinc-induced fluorescence response. DA-ZP1-TPP is insensitive to intracellular esterases over a 2-h period and is impervious to proton-induced turn-on. A TPP unit is appended for targeting mitochondria, as demonstrated by live cell fluorescence imaging studies. The practical utility of DA-ZP1-TPP is demonstrated by experiments revealing that, in contrast to healthy epithelial prostate cells, tumorigenic cells are unable to accumulate mobile zinc within their mitochondria.

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