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Real-time monitoring of the cytochrome P450 1A1 (CYP1A1) activity in complex biological systems via a practical tool is highly sought after because of its significant role in the metabolism and bioactivation of various xenobiotics. Herein, according to slight differences in the 3D structure and substrate preference between CYP1A1 and its homologous CYP1A2, a series of novel ratiometric fluorescent probes were designed and synthesized using 1,8-naphthalimide because of its trait of naked-eye visualization and ratiometric fluorescence to achieve the detection of CYP1A1 in biological samples. Among these probes, NEiPN showed good water solubility, highly isoform selectivity and great sensitivity (LOD = 0.04874 nM) for CYP1A1 under simulated physiological conditions, which makes it favorable for monitoring CYP1A1 in vivo. Remarkably, NEiPN exhibited excellent reproducibility when it was used to detect the CYP1A1 content in human liver microsomes, which indicated that it has a great potential for quantifying the CYP1A1 content in real biological samples. Furthermore, NEiPN showed relatively low cytotoxicity and has been successfully applied in biological imaging in living cells and zebrafish. These findings indicate that NEiPN is capable of real-time monitoring of the activity of endogenous CYP1A1, which could provide support for CYP1A1-associated pathological processes. [ABSTRACT FROM AUTHOR]

In most biophysiological processes, sulfur dioxide (SO 2) is an important intracellular signaling molecule that plays an important role. The change of SO 2 in cells are closely related to various diseases such as neurological disorders and lung cancer, so it is necessary to develop fluorescent probes with the ability to accurately detect SO 2 during physiological processes. In this work, we designed and synthesized a multifunctional fluorescent probe TIS. TIS has excellent properties such as near-infrared emission, large stokes shift, excellent SO 2 detection capabilities, low detection limit, high specificity and visualization of color change before and after reaction. Simultaneously, TIS has low cytotoxicity, good biocompatibility, clear cell imaging capability and mitochondrial targeting ability. In addition, the ability of TIS to be applied to different material surfaces for latent fingerprint fluorescence imaging was also explored. TIS provides an excellent method for the accurate detection of SO 2 derivatives and shows great potential applications in near-infrared cellular imaging and latent fingerprint fluorescence imaging. (a) TIS response mechanisms for HSO 3 −. (b) application of TIS. [Display omitted] • A NIR emission fluorescent probe with AIE characterization. • TIS has long emission wavelength (795 nm) and large Stokes shift (265 nm). • Dual detection channel for SO 2 derivatives accurate detection. • Superior colocalization effect on mitochondrial (0.86). • Clear three-level finger imaging capability. [ABSTRACT FROM AUTHOR]

[Display omitted] • TCN-2 has excellent viscosity response characteristics. • TCN-2 could achieve lipid droplets targeting and induce tumor cell death. • TCN-2 induced the generation of large amounts of non-oxygen consuming ROS. A dual donor–acceptor photosensitizer TCN-2 prepared based on single donor–acceptor could fulfil lipid droplets targeting to trigger apoptosis and tumor growth arrest. Meanwhile, all of experiments both in phosphate buffer solution and intracellular surroundings have demonstrated that TCN-2 catalyzed the production of type I as well as type II reactive oxygen species, forming a hybrid reactive oxygen species pattern, indicating that TCN-2 could be applied to initiate a series of biological responses triggered by oxidative stress within most high-viscosity solid tumors. In addition, TCN-2 also has the capability of fluorescence imaging, which could perfectly combine therapeutic imaging to achieve therapeutic effects while identifying cancerous lesions. Due to the structural design of double electron-absorbing groups, TCN-2 retained excellent lipophilicity while enhancing solubility in the biological environment. Terrific biocompatibility, minimal phototoxic damage to normal cells and tissues, and specific driving to prescriptive organelles to maximize therapeutic effects were used to enhance the therapeutic effect of photodynamic therapy to cease disease progression. [ABSTRACT FROM AUTHOR]

Targeting the organelles that generate oxidative stress and implementing oxidative stress therapy is an essential and ambitious task. As an important subcellular organelle in eukaryotic cells, the endoplasmic reticulum (ER) is significant in mediating the direction of cell metabolism and apoptosis. To achieve the goal, we rationally designed and synthesized a photosensitizer named TTQ-ER with aggregation-induced emission (AIE) characteristics. Such a probe connects the AIE-fluorophore to the glibenclamide backbone, which enables TTQ-ER to specifically target the ER and promote emission in the near-infrared region, avoiding the negative impact of autofluorescence in organisms. Meanwhile, TTQ-ER has a large stokes shift, excellent anti-photobleaching properties, and sufficient 1O 2 production (8.85-fold of Ce6). Apoptosis assay and cell migration assay further verified that excessive reactive oxygen species production by TTQ-ER in cancer cells could promote oxidative stress in the ER microenvironment and disrupt the normal biological function of ER, thus causing elevated local lipid peroxidation and inducing apoptosis in cancer cells. Consequently, this work offers informative ideas for designing a newly generation of photosensitizers to achieve accurate photodynamic therapy. Schematic diagram of TTQ-ER promoting apoptosis of cancer cells. [Display omitted] • TTQ-ER possesses bright NIR emission, large stokes shifts and precise ER targeting. • Significant ER-targeted specificity (Rr = 0.903). • Extremely high generation yield of 1O 2 (8.85-fold that of Ce6). • Superior photodynamic ablation of cancer cells. [ABSTRACT FROM AUTHOR]

• This strategy is the first report of a near-infrared fluorescent probe for detecting CYP1A1. • This NIR fluorescent probe reveals ultrasensitive sensitivity (minimum detectable limit is 0.026 nM), lower than that of the previously reported probe. • The size of the O-chloroethyl group is suitable for the cavity volume of the active sites of CYP1A1 and the lipophilicity and polarity of the group make the probe suitable for oriented at the actives sites. • The prominent Stokes Shift (118 nm) contribute to probe serving as a "naked-eye" efficient tool for indicating CYP1A1. Human cytochrome P450 1A1 (CYP1A1) enzyme is involved in the oxidation of various procarcinogenes into active carcinogenic metabolites in the phase I of biotransformation and initiates the carcinogenic process. Here, a novel ultrasensitive CYP1A1-specific fluorescent probe (DPCl) was investigated deeply which has O-chloroethyl group as a trigger for CYP1A1 activity and a dicyanoisophorone derivative fluorophore with a 673 nm emission. The size of the O-chloroethyl group is suitable for the cavity volume of the active sites of CYP1A1 and the lipophilicity and polarity of the group make the probe suitable for oriented at the actives sites. Hence, this near-infrared fluorescent probe reveals ultrasensitive sensitivity (minimum detectable limit is 0.026 nM), excellent specificity, and low toxicity in the process of target enzyme monitoring under simulated physiological condition, living cells and zebrafish. The success of this strategy is rely on intermediate product (DPOH) after dechloroethylation of DPCl is NIR-illuminant platform with a prominent Stokes Shift (118 nm), which is the first report of a NIR fluorescent probe for detecting CYP1A1. Anyhow, this probe provides support for clinical studies of CYP1A1 cell screening inhibitors and real-time tracking of enzyme activity in vivo. [ABSTRACT FROM AUTHOR]

Abstract Cysteine(Cys) is tightly related to physiological and pathological of human, and the imbalance of concentration of cysteine in the intracellular are associated with many diseases. Here, a novel NIR fluorescent probe TCF-Cys was designed and synthesized, and both the optimal excitation and emission wavelength of them were between 650 and 900 nm, that within the "optical window" of biological tissues. In aqueous solution, TCF-Cys , which with an acrylate extremity as a recognizing unit, exhibited excellent "turn-on" fluorescence response for Cys superior to other amino acids and thiols with a limit of detection of 0.1323 μM. Moreover, as an excellent naked-eye colorimetric indicator, TCF-Cys could effectively distinguishing the Cys, Hcy and GSH in aqueous solution through color change. Then, the response mechanism of TCF-Cys for Cys was revealed by TLC, 1H NMR, HPLC, HRMS and DFT calculation. Finally, TCF-Cys was successfully employed to fluorescence specifically map of exogenous and endogenous Cys in living cells and zebrafish with low toxicity. Graphical abstract A novel probe TCF-Cys for colorimetric and NIR fluorescent detection of Cys in aqueous solution and fluorescence imaging endogenous and exogenous Cys in living HeLa cells and zebrafish. Unlabelled Image Highlights • Novel NIR fluorescent probes TCF-Cys was designed and synthesized. • TCF-Cys showed selective "turn-on" fluorescence response to Cys in solution. • Cys, Hcy and GSH were distinguished by TCF-Cys through the solution color change. • The mechanism was studied by TLC, 1H NMR, HPLC, HRMS and DFT calculation. • TCF-Cys has been successfully utilized to image living cells and zebrafish. [ABSTRACT FROM AUTHOR]

Abstract Fast, highly selective and sensitive thiophenol probes are highly desirable in the field of bioimaging and environmental monitoring. For that, based on the mechanism that thiophenol can effectively cleave the sulfonamide bond selectively, we herein report a dicyanoisophorone-based Red-emitting/NIR probe for thiophenol detection. This probe had some desirable properties such as rapid response, high selectivity and sensitivity, remarkable large Stokes shift (181 nm), Red-emitting/NIR fluorescence region and low LOD value (80 nM, according to 3σ/s). Moreover, this novel Red-emitting/NIR probe can potentially be applied to the detection of thiophenols in real water samples quantitatively and fluorescent imaging in living cells and zebrafishes. Graphical Abstract Unlabelled Image Highlights • Probe with dicyanoisophorone has good membrane permeability and large Stokes shift. • Ideal fluorescence intensity and red-emitting/NIR emission (650 nm) • Instantaneous response (few seconds) and intensity levelled off within 7 min. • Probe has High selectivity. • Application in real water sample and cell even in vivo(zebrafish) [ABSTRACT FROM AUTHOR]

Abstract A novel near-infrared fluorescent probe RHCC was devised and synthesized. It exhibits high specificity to Fe3+ compared to other metals in aqueous solutions. The detection limit of RHCC was 1.2 × 10−7 M and the complexation stability constant was 5.807 × 104 M−1. The binding ratio of RHCC and Fe3+ was 1:1 which was measured through MS, FTIR and Job's plot. The energy gap between HOMO and LUMO of RHCC was 3.22 eV, while RHCC- Fe3+ complex was 0.95 eV. This result means the binding of probe RHCC and Fe3+ lowers the RHCC- Fe3+ complex's energy gap and makes it more stable. What's more, in living cells and zebrafishes studies, probe RHCC was no significant cytotoxic effect, indicating it could monitor Fe3+ in biological system. Graphical abstract fx1 Highlights • A novel near-infrared "turn-on" fluorescent probe RHCC had been synthesized. • The probe RHCC exhibits high sensitivity and excellent selectivity to Fe3+. • The probe RHCC can be used for characteristic 'naked-eye' detection of Fe3+. • The probe RHCC can monitor Fe3+ in biological system. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) combined with critical organelle targeting can maximize ablation of malignant tumors, which is a desirable route against cancer. However, the short excitation/emission wavelengths of conventional photosensitizers (PSs), the inefficient production of reactive oxygen species (ROS) and the inevitable aggregation-induced quenching phenomenon have restricted their development. Herein, we developed and synthesized a set of photoactivated fluorescent probes named MoTQu and MeTQu with aggregation-induced emission properties. The both of fluorescent probes have merits of bright near-infrared fluorescence emission, large stokes shift and enhanced intramolecular charge transfer attributed to the synergistic interaction of strong donor and acceptor of molecular. In addition, the optimal PS named MoTQu not only possesses superior anti-photobleaching, biocompatibility and extremely high-level ROS generation efficiency, on the other hand, can time-responsive target mitochondria and lysosomes in living cells to cause lysosomal dysfunction by generating large amount of ROS in situ under photoexcitation, subsequently targeting mitochondria through the positive electrical properties of the quinoline fraction, further inducing and promoting cancer cell damage and irreversible apoptosis. Consequently, we are convinced that MoTQu can be a powerful tool to foster the development of image-guided PDT. [Display omitted] • MoTQu has merit of time-responsive mitochondria and lysosomes targeting. • MoTQu have desirable advantages of large stokes shifts and bright NIR emission. • The sufficient ROS generation of MoTQu upon photoexcitation can ablate cancer cells. • Tiny doses of MoTQu under photoexcitation could suppress metastasis of cancer cells. [ABSTRACT FROM AUTHOR]

A near-infrared (NIR) and colorimetric fluorescent probe system was developed for Carbon Monoxide (CO) via a Pd 0 -mediated Tsuji-Trost reaction. In this probe, phenoxide anion formation (DPCO − ) was acted as the signal unit and an allyl carbonate group was used as the recognition unit. This non-fluorescent probe molecule can release the relevant fluorophore after conversion of Pd 2+ to Pd 0 by CO. The probe system including probe 1 and Pd 2+ can be used for “naked-eye” detection of CO, and exhibited high selectivity to CO over various other sensing objects. More importantly, the probe system has great potential for fluorescence imaging of intracellular CO in living cells. [ABSTRACT FROM AUTHOR]

Cytochrome P450s have brought considerable attention to researchers for their significant correlations with metabolic behaviors of procarcinogenic chemicals. To better understand the roles of CYP1A in biological and physiological systems, we developed a novel ratiometric fluorescence probe N-((2-hydroxyl ethoxy) ethyl)− 4-methoxy-1, 8-naphthalimide ( NEMN ) allowing for selectively and sensitively monitoring the target enzymes under physiological conditions and living cells. The probe was designed based on substrate predilection of CYP1A and its outstanding O-dealkylation capacity, and 1, 8-naphthalimide was chosen as fluorophore on account of its desirable photophysical properties. Absorption and emission spectra of the probe solution and reacted metabolism showed obvious red-shift with remarkable colour changes, which indicated that NEMN could be a promising ratiometric detector of CYP1A. Additionally, the selectivity assays displayed that NEMN only sensitive to CYP1A1 and CYP1A2 enzymes with scarce interference of other CYPs. Furthermore, the excellent linear relationships between the ratio of fluorescent intensities and incubation time and enzymes concentration signified time- and concentration- dependence of the probe, which were of desire benefit to quantify and monitor the CYP1A-involved biological behaviors in physiological conditions. The assay in real living samples (Human liver microsomes) further proved the analytical utility of the probe. Finally, the cytotoxicity assay and confocal fluorescence imaging demonstrated that this probe was of great promise for detecting the activity of endogenous CYP1A in human living cells. [ABSTRACT FROM AUTHOR]

The probe CT was synthesized and investigated as a novel label-free chemosensor for Ga 3 + detection in water. Probe CT showed remarkable selectivity and sensitivity for Ga 3 + in Tris–HCl aqueous buffer solution (pH 7.0). The chemosensor responded rapidly to Ga 3 + with a 1:1 stoichiometry. Meanwhile, the unapparent changes of fluorescence lifetime decays suggest the turn-on process of probe CT by Ga 3 + which appears to be a static mechanism. [ABSTRACT FROM AUTHOR]

• Detecting CYP3A5 activity using fluorescent probe for the first time. • Excellent sensitivity (LOD = 0.04581 nM) was realized in Hcy-Br. • Hcy-Br possessing Preferable mitochondria-specific targeting (Rr = 0.8746). • Visualization of living cells and tumor-bearing mice was achieved in Hcy-Br. Cytochrome P450 (CYP) 3A5 as the most important CYPs in the CYP3A isoform, is polymorphic and plays a significant role in drug metabolism. Herein, two novel enzyme-activatable near-infrared (NIR) ratiometric fluorescent probes (Hcy-Br and Hcy-Cl) are designed and synthesized to measure the activity of CYP3A5 in complex biological systems. Hcy-Br possesses excellent sensitivity in response to CYP3A5 enzyme with the LOD = 0.04903 nM and could quickly reach equilibrium within 30 min. The ability of targeting mitochondria, along with preferable Pearson's correlation coefficients (Rr) of 0.8746, is realized in Hcy-Br. The application of Hcy-Br in living cells and tumor-bearing mice is also achieved successfully for monitoring endogenous CYP3A5 activity. Detecting CYP3A5 activity in living system via fluorescent probe, to the best of our knowledge, is reported for the first time. These findings suggest that Hcy-Br could be served as a useful tool for selectively detecting the activity of endogenous CYP3A5 in vivo, providing assistance for investigating the function of CYP3A5 in drug metabolism and pathologic process. [ABSTRACT FROM AUTHOR]

Cytochrome P450 2J2 (CYP2J2) is overexpressed in human carcinoma cells lines and malignant tumors, and has been closely related to the pathogenesis of cancers and further deterioration of the tumor. However, the molecular tools used for In Situ monitoring CYP2J2 are still rarely reported due to the multiplex of CYP2J2 enzyme structure and biological sample. Herein, a near-infrared (NIR) fluorescent probe (DPBM) with large Stokes shift (118 nm) for detection CYP2J2 was developed based on three-fragmentary molecular assembly engineering. The DPBM exhibited excellent specificity, high sensitivity and rapid 'turn-on' NIR emission for CYP2J2 relative to other CYP isoforms in the simulated physiological environment. The limit of detection of DPBM was calculated to be 0.09 nM for CYP2J2, insinuating that DPBM would be sensitive enough to perceive endogenous CYP2J2 activity. Indeed, the DPBM was successfully applied for real-time and long-term monitoring and bio-imaging of CYP2J2 activity in human liver microsomes (HLMs), living cells, isolated organs and In Situ tumor-bearing BALB/c nude mice. These findings insinuate that DPBM can accurately sense CYP2J2 enzyme activity in vitro/vivo , which maybe facilitate further explorations of physiological and pathological processes of CYP2J2-associated diseases. [ABSTRACT FROM AUTHOR]

Cysteine (Cys), an important organic small molecule containing sulfhydryl groups, plays paramount functions in human pathologies and physiologies. The detection of Cys in living vivo is essential for studying its roles. Here, we designed and synthesized a novel red-emission fluorescent probe AXPI-Cys with highly sensitivity (LOD = 48.9 ± 0.23 nM), rapidly response (<7 min) and colorimetric for detection cysteine. More importantly, the AXPI-Cys was determined Cys in real cystinuria urine samples for the first time with the satisfactory results (92%–99.96%) and employed for specifically location of endogenous/exogenous Cys in living cancer/normal cells and almost non-toxic, that is very valuable for diagnosis of cystinuria and observation of the distribution of Cys in normal cells. Notably, the AXPI-Cys was applied to imaging Cys in BALB/c nude mice with good biocompatibility and desirable tissue-penetration depth. Owing to the superior capability of AXPI-Cys , it provided a desired method to detect Cys in urine samples and cells, and exhibited munificent potential usage in biosystems and imaging studies in vivo. Unlabelled Image • A water soluble red-emission fluorescent probe (AXPI-Cys) was developed. • AXPI-Cys was used to determine Cys in real cystinuria urine samples with the satisfactory recovery. • AXPI-Cys was employed map location Cys in living HepG2/LO2 cells with almost non-toxi. • AXPI-Cys was applied for rapidly detection Cys in mice with desirable biocompatibility and tissue-penetration depth. [ABSTRACT FROM AUTHOR]

Reactive sulfur species (RSS), primarily containing glutathione (GSH), cysteine (Cys), hydrogen sulfide (H 2 S) and hydrogen polysulfides (H 2 S n , n > 1), were crucial endogenous biological signal molecules. Among them, H 2 S and H 2 S n played extremely momentous roles in many physiological and pathological processes. Limited by the vivo environmental diversity and complexity, it was highly desirable to rely on the single fluorescence probe platform to visualize H 2 S n and H 2 S according different fluorescence signals. Herein, we reported a two-photon excited fluorescent probe MC-S n that had the following merits: (Ⅰ) ratiometric and colorimetric: reducing detection errors and conducting visual analysis; (Ⅱ) two-photon microscope: better performance in vivo and vitro imaging; (Ⅲ) two specific sulfide reaction sites: studying on the mutual transformation of H 2 S n and H 2 S in biological systems. Furthermore, take advantages of low cytotoxicity (cell viability ≥ 85.99%), low limit of detection (21 nM), significant photostability, excellent pH stability, quick response behavior (175 s) and high penetration depth (110 μm), MC-S n can be employed to visualize endogenous and exogenous H 2 S n and H 2 S in cells, liver tissues and zebrafish. • Ratiometric and colorimetric: reducing detection errors and conducting visual analysis. • Two-photon microscope: better performance in vivo and vitro imaging. • Two specific sulfide reaction sites: studying on the mutual transformation of H2Sn and H2S in biological systems. • Low limit of detection (21 nM) and high penetration depth (110 μm). [ABSTRACT FROM AUTHOR]