Sensing Performance Enhancement via Acetate-Mediated N-Acylation of Thiourea Derivatives: A Novel Fluorescent Turn-On Hg²⁺ Chemodosimeter

A Hg²⁺ chemodosimeter <b>P3</b> derived from a perylenebisimide scaffold and thiourea fragments was systematically studied with focus on the photophysical, chemodosimetric mechanistic, as well as fluorogenic behaviors toward various metal cations for the sake of improving selectivity to Hg²⁺. As demonstrated, Hg²⁺ can promote a stepwise desulfurization and N-acylation of <b>P3</b> with the help of an acetate anion (OAc^–), resulting in an N-acylated urea derivative. Interestingly, OAc^– has the effect of improving the selectivity of <b>P3</b> to Hg²⁺ among other metal ions; that is, in an acetone/Britton–Robinson buffer (9:1, v/v; pH 7.0) upon excitation at 540 nm, the relative fluorescence intensity is increased linearly with increasing concentration of Hg²⁺ in the range of 2.5–20 μM with a detection limit of 0.6 μM, whereas the fluorescence intensity of <b>P3</b> to other metal ions, including Na⁺, K⁺, Mg²⁺, Ca²⁺, Mn²⁺, Fe²⁺, Ni²⁺, Co²⁺, Zn²⁺ Ag⁺, Cd²⁺, Pb²⁺, and Cu²⁺, is negligible. The fluorescent bioimaging of chemodosimeter <b>P3</b> to detect Hg²⁺ in living cells was also reported

A Multiaddressable Photochromic Bisthienylethene with Sequence-Dependent Responses: Construction of an INHIBIT Logic Gate and a Keypad Lock

A photochromic bisthienylethene derivative (<b>BIT</b>) containing two imidazole units has been synthesized and fully characterized. When triggered by chemical ions (Ag⁺), protons, and light, <b>BIT</b> can behave as an absorbance switch, leading to a multiaddressable system. <b>BIT</b> exhibits sequence-dependent responses via efficient interaction of the specific imidazole unit with protons and Ag⁺. Furthermore, an INHIBIT logic gate and a keypad lock with three inputs are constructed with the unimolecular platform by employing an absorption mode at different wavelengths as outputs on the basis of an appropriate combination of chemical and photonic stimuli

Screen-Printed Red Luminescent Copolymer Film Containing Cyclometalated Iridium(III) Complex as a High-Permeability Dissolved-Oxygen Sensor for Fermentation Bioprocess

The novel hydrophobic luminescent copolymer P­(Ir-TFEMA) was developed as an online dissolved-oxygen (DO) sensor. The phosphorescent moiety of cyclometalated iridium­(III) complex exhibits red emission near 650 nm with a large Stokes shift of about 245 nm and minimal optical interference from the fermentation system. The covalent incorporation of the chromophore into the polymeric matrix rather than physical doping was used to avoid phase-separation and leaching problems. The low molar ratio between the introduced chromophore and polymeric matrix within the range of 1:135–1:250 was confirmed to have little influence on the luminescence response ability. To assess its potential utility, this copolymer was applied to the online monitoring of DO during the cephalosporin C fermentation process. The screen-printing technique was utilized as a rapid and reliable automatic approach to preparing sensor films with good photostability and fatigue resistance, showing promise in bioprocess monitoring as a low-cost DO indicator for high-throughput microbioreactors

Optimizing the Chemical Recognition Process of a Fluorescent Chemosensor for α‑Ketoglutarate

α-Ketoglutarate (α-KA) can convert to 2-hydroxyglutarate (2-HG), which is confirmed to be associated with many diseases, especially with acute myeloid leukemia (AML). In this paper, a novel reaction-based chemosensor DT based on the typical Schiff-base reaction was designed for sensing the biomarker of α-KA, in which a diazanyl group as the recognition group was linked with a benzothiadiazole unit as the fluorophore moiety. Considering the typical Schiff-base reaction to generate hydrazones suffering from slow kinetics, particularly under neutral conditions, a series of parallel experiments was conducted for optimizing the chemical recognition process, including varying the solvent, reaction temperature, reactant concentration, and reaction rate. The optimum condition was established as a pH value, temperature, α-KA concentration, and response time of 5.7, 30 °C, 100 μM, and 20 min, respectively. Notably, in contrast with the initial 6.3-fold fluorescence enhancement, the remarkable 75-fold fluorescence enhancement ((<i>I</i> – <i>I</i>₀)/<i>I</i>₀ at 560 nm) was observed by optimizing the chemical recognition process of DT and α-KA. Finally, DT was carried out for the chemical recognition processing of α-KA in serum. We demonstrated that DT is selective for α-KA over other potential biologically interferences with similar structures and thus is suitable for detecting α-KA in serum. On the basis of the optimized chemical recognition process, DT shows high potential application for sensing α-KA with remarkable fluorescence enhancement. This work provided a potential method that is quick and convenient for sensing biomarker α-KA in serum. It is worth noting that without complicated pretreatment, utilizing a novel reaction-based fluorescent chemosensor may establish a new promising platform for clinical diagnosis biomarker

Near-Infrared Colorimetric and Fluorescent Cu²⁺ Sensors Based on Indoline–Benzothiadiazole Derivatives via Formation of Radical Cations

The donor–acceptor system of indoline–benzothiadiazole is established as the novel and reactive platform for generating amine radical cations with the interaction of Cu²⁺, which has been successfully exploited as the building block to be highly sensitive and selective near infrared (NIR) colorimetric and fluorescent Cu²⁺ sensors. Upon the addition of Cu²⁺, an instantaneous red shift of absorption spectra as well as the quenched NIR fluorescence of the substrates is observed. The feasibility and validity of the radical cation generation are confirmed by cyclic voltammetry and electron paramagnetic resonance spectra. Moreover, the introduction of an aldehyde group extends the electron spin density and changes the charge distribution. Our system demonstrates the large scope and diversity in terms of activation mechanism, response time, and property control in the design of Cu²⁺ sensors

<i>In Vivo</i> and <i>in Situ</i> Tracking Cancer Chemotherapy by Highly Photostable NIR Fluorescent Theranostic Prodrug

<i>In vivo</i> monitoring of the biodistribution and activation of prodrugs is urgently required. Near infrared (NIR) fluorescence-active fluorophores with excellent photostability are preferable for tracking drug release <i>in vivo</i>. Herein, we describe a NIR prodrug DCM-S-CPT and its polyethylene glycol–polylactic acid (PEG-PLA) loaded nanoparticles as a potent cancer therapy. We have conjugated a dicyanomethylene-4<i>H</i>-pyran derivative as the NIR fluorophore with camptothecin (CPT) as the anticancer drug using a disulfide linker. <i>In vitro</i> experiments verify that the high intracellular glutathione (GSH) concentrations in tumor cells cause cleavage of the disulfide linker, resulting in concomitantly the active drug CPT release and significant NIR fluorescence turn-on with large Stokes shift (200 nm). The NIR fluorescence of DCM-S-CPT at 665 nm with fast response to GSH can act as a direct off–on signal reporter for the GSH-activatable prodrug. Particularly, DCM-S-CPT possesses much better photostability than ICG, which is highly desirable for <i>in situ</i> fluorescence-tracking of cancer chemotherapy. DCM-S-CPT has been successfully utilized for <i>in vivo</i> and <i>in situ</i> tracking of drug release and cancer therapeutic efficacy in living animals by NIR fluorescence. DCM-S-CPT exhibits excellent tumor-activatable performance when intravenously injected into tumor-bearing nude mice, as well as specific cancer therapy with few side effects. DCM-S-CPT loaded in PEG-PLA nanoparticles shows even higher antitumor activity than free CPT, and is also retained longer in the plasma. The tumor-targeting ability and the specific drug release in tumors make DCM-S-CPT as a promising prodrug, providing significant advances toward deeper understanding and exploration of theranostic drug-delivery systems

Self-Assembly Solid-State Enhanced Red Emission of Quinolinemalononitrile: Optical Waveguides and Stimuli Response

The fluorescence of luminescent emitters is often quenched in the solid state, because of the typical aggregation-caused quenching (ACQ) effect, which is a thorny obstacle to high-performance organic optoelectronic materials. The exploration of solid-state enhanced long wavelength, red-emitting chromophores, especially possessing one-dimensional (1D) assembly features, is of great importance. Interestingly, an excellent solid-state enhanced red emission system (denoted as ED) based on quinolinemalononitrile has been developed via the delicate modification of the conventional ACQ dicyanomethylene-4<i>H</i>-pyran (DCM) derivative (denoted as BD) through crystal engineering. ED exhibits extraordinary self-assembly property in a variety of solvents, even realizing the “waving ribbons” with a length of 6 mm and a diameter of 10 μm. Crystal analysis shows that the CH···π and CH···N supramolecular interactions of ED contribute to the twisted self-assembly solid-state enhanced emission phenomenon. However, for BD, strong face-to-face stacking leads to fluorescence quenching in the solid state. Because of such easy assembly and strong solid-state emission properties, application for optical waveguides of ED is realized with a low optical loss. Stimuli-responsive behavior is also elaborated with color change between orange and red by grinding/fuming or pressing/heating

In Situ Ratiometric Quantitative Tracing of Intracellular Leucine Aminopeptidase Activity via an Activatable Near-Infrared Fluorescent Probe

Leucine aminopeptidase (LAP), one of the important proteolytic enzymes, is intertwined with the progress of many pathological disorders as a well-defined biomarker. To explore fluorescent aminopeptidase probe for quantitative detection of LAP distribution and dynamic changes, herein we report a LAP-targeting near-infrared (NIR) fluorescent probe (DCM–Leu) for ratiometric quantitative trapping of LAP activity in different kinds of living cells. DCM–Leu is composed of a NIR-emitting fluorophore (DCM) as a reporter and l-leucine as a triggered moiety, which are linked together by an amide bond specific for LAP cleavage. High contrast on the ratiometric NIR fluorescence signal can be achieved in response to LAP activity, thus enabling quantification of endogenous LAP with “build-in calibration” as well as minimal background interference. Its ratiometric NIR signal can be blocked in a dose-dependent manner by bestatin, an LAP inhibitor, indicating that the alteration of endogenous LAP activity results in these obviously fluorescent signal responses. It is worth noting that DCM–Leu features striking characteristics such as a large Stokes shift (∼205 nm), superior selectivity, and strong photostability responding to LAP. Impressively, not only did we successfully exemplify DCM–Leu in situ ratiometric trapping and quantification of endogenous LAP activity in various types of living cells, but also, with the aid of three-dimensional confocal imaging, the intracellular LAP distribution is clearly observed from different perspectives for the first time, owing to the high signal-to-noise of ratiometric NIR fluorescent response. Collectively, these results demonstrate preclinical potential value of DCM–Leu serving as a useful NIR fluorescent probe for early detection of LAP-associated disease and screening inhibitor

Facile Preparation of AIE-Active Fluorescent Nanoparticles through Flash Nanoprecipitation

Flash nanoprecipitation (FNP) is an easily scalable and fast processing method for the preparation of nanoparticles (NPs) with simple vortex equipment. By using the FNP method, fluorescent NPs are prepared in less than 1 s in a multi-inlet vortex mixer, in which hydrophobic aggregation-induced emission (AIE)-active dye of EDP is incorporated within the biocompatible block copolymer poly­(ethylene glycol)-<i>b</i>-poly­(ε-caprolactone) for EDP NP assembly. The formulation parameters of stream velocity, dyes, and loading and concentration in FNP are optimized. The sizes of the NPs ranged from 20 to 60 nm with a ratio change of mixed solvents. As a control, an aggregation-caused quenching (ACQ) molecule of BDP was also synthesized for BDP NPs. To gain insight into the effect of the polymer on the aggregation state of hydrophobic dyes, the preparation of EDP and BDP NPs without block copolymer was also investigated. Apparently, the sizes of the NPs display large distributions without an amphiphilic block copolymer as the engineering template, suggesting that the block of polymers plays a key role in tuning the aggregation state of encapsulated dyes in FNP processes. Moreover, the peak shifts of dye with different microenvironments also confirmed the successful encapsulation of fluorescent dye in the NP cores. Finally, by externally applied forces in the FNP method, the engineered assembly of AIE-active fluorescent NPs possessing a narrow size distribution with desirable fluorescence properties was obtained. These features provide the possibility of rapidly constructing controllable AIE-active fluorescent NPs as biomedical tracers

Facile Preparation of AIE-Active Fluorescent Nanoparticles through Flash Nanoprecipitation

Flash nanoprecipitation (FNP) is an easily scalable and fast processing method for the preparation of nanoparticles (NPs) with simple vortex equipment. By using the FNP method, fluorescent NPs are prepared in less than 1 s in a multi-inlet vortex mixer, in which hydrophobic aggregation-induced emission (AIE)-active dye of EDP is incorporated within the biocompatible block copolymer poly­(ethylene glycol)-<i>b</i>-poly­(ε-caprolactone) for EDP NP assembly. The formulation parameters of stream velocity, dyes, and loading and concentration in FNP are optimized. The sizes of the NPs ranged from 20 to 60 nm with a ratio change of mixed solvents. As a control, an aggregation-caused quenching (ACQ) molecule of BDP was also synthesized for BDP NPs. To gain insight into the effect of the polymer on the aggregation state of hydrophobic dyes, the preparation of EDP and BDP NPs without block copolymer was also investigated. Apparently, the sizes of the NPs display large distributions without an amphiphilic block copolymer as the engineering template, suggesting that the block of polymers plays a key role in tuning the aggregation state of encapsulated dyes in FNP processes. Moreover, the peak shifts of dye with different microenvironments also confirmed the successful encapsulation of fluorescent dye in the NP cores. Finally, by externally applied forces in the FNP method, the engineered assembly of AIE-active fluorescent NPs possessing a narrow size distribution with desirable fluorescence properties was obtained. These features provide the possibility of rapidly constructing controllable AIE-active fluorescent NPs as biomedical tracers