A novel fluorescence probe for simultaneous detection of mitochondrial viscosity in hepatic ischemia reperfusion injury models.

Acute liver failure caused by hepatic ischemia reperfusion injury (HIRI) poses a severe threat to life, emphasizing the urgent need for precise and timely early diagnosis. Viscosity, a key parameter reflecting active analyte levels at the cellular level, remains underexplored in relation to HIRI. To address this gap, we have developed a groundbreaking near-infrared molecule rotator, PN, exhibiting exceptional characteristics. PN demonstrates remarkable sensitivity, with a 32-fold change in response to viscosity, ranging from PBS to glycerol solution. PN's distinctive features include maximum emission wavelength 790 nm, as well as an impressive Stokes shift 190 nm. Moreover, PN exhibits the ability to sensitively and selectively differentiate nystatin-induced viscosity changes within living cells, and can be used for the detection of viscosity changes in the HIRI mouse model. This capability enhances our understanding of cellular responses, opening avenues for potential applications within disease models. The versatility of PN extends to its potential role in guiding timely monitoring and imaging of viscosity, offering valuable insights into disease progression.

Development of a novel near-infrared molecule rotator for early diagnosis and visualization of viscosity changes in acute liver injury models.

Acute liver injury leading to acute liver failure can be a life-threatening condition. Therefore, timely and accurate early diagnosis of the onset of acute liver injury in vivo is critical. Viscosity is one of the key parameters that can accurately reflect the levels of relevant active analytes at the cellular level. Herein, a novel near-infrared molecule rotator, DJM, was designed and synthesized. This probe exhibited a highly sensitive (461-fold from PBS solution to 95% glycerol solution) and selective response to viscosity with a maximum emission wavelength of 760 nm and a Stokes shift of 240 nm. Furthermore, DJM has exhibited a remarkable capacity to discern viscosity changes induced by nystatin in viable cells with sensitivity and selectivity and further applied in the zebrafish and mouse model of acute liver injury. Additionally, DJM may potentially offer direction for the timely observation and visualization of viscosity in more relevant disease models in the future.

Modular synthesis of clickable peptides via late-stage maleimidation on C(7)-H tryptophan.

Cyclic peptides have attracted tremendous attention in the pharmaceutical industry owing to their excellent cell penetrability, stability, thermostability, and drug-like properties. However, the currently available facile methodologies for creating such peptides are rather limited. Herein, we report an efficient and direct peptide cyclization via rhodium(III)-catalyzed C(7)-H maleimidation. Notably, this catalytical system has excellent regioselectivity and high tolerance of functional groups which enable late-stage cyclization of peptides. This architecture of cyclic peptides exhibits higher bioactivity than its parent linear peptides. Moreover, the Trp-substituted maleimide displays excellent reactivity toward Michael addition, indicating its potential as a click functional group for applications in chemical biology and medicinal chemistry. As a proof of principle, RGD-GFLG-DOX, which is a peptide-drug-conjugate, is constructed and it displays a strong binding affinity and high antiproliferative activity toward integrin-αvß3 overexpressed cancer cell lines. The proposed strategy for rapid preparation of stapled peptides would be a robust tool for creating peptide-drug conjugates.

Recent progress on small molecular temperature-sensitive fluorescent probes.

Temperature is an important biophysical parameter that is closely related with the metabolic activity in living cells. Therefore, the detection of intracellular temperature changes is crucial for exploring temperature-related biological processes. Fluorescence probe is an ideal tool for observing temperature changes in cells, which has many advantages, such as high sensitivity, good selectivity, and noninvasive, and thus aroused the great interest of researchers. In this paper, we summarize the recent progress of organic small molecule temperature-sensitive fluorescence probes in recent years was reviewed. Particularly, we describe the common response mode to the temperature and the practical applications of the probe in living cells and even animal models. Moreover, an outlook regarding temperature detection in clinical applications is discussed. The temperature-sensitive fluorescent probe is a "black box" to many researchers. This review aims to open a window on the prospect of the noninvasive in vivo detection of temperature which is helpful to deeper understand this rich research area.

Ultrasensitive Small-Molecule Fluorescent Thermometer Reveals Hot Mitochondria in Surgically Resected Human Tumors.

The Warburg effect suggests that upregulated glycolysis arising from high glucose uptake in cancer cells might be accompanied with suppressed mitochondrial respiration. However, recent studies have shown that the mitochondrial temperature in cancer cells could be relatively higher than that in normal cells, suggesting hyperactive mitochondrial respiration in cancer cells. However, hot mitochondria have not been reported in patients with cancer. Here, near-infrared small-molecule fluorescent probes TRNs are rationally designed with two ethyl amino groups as the temperature-sensitive moiety. Afterward, a mitochondrial targeting group is installed via ether bonds on TRN-8 to build MTN. To the best of our knowledge, MTN is the near-infrared probe with the highest sensitivity for mitochondrial temperature. Moreover, it also displays high photostability, wide linearity, and high specificity. Using MTN, we can monitor the ups and downs of mitochondrial temperature in cancer cells upon the perturbations of mitochondrial respiration. Furthermore, we demonstrate that the mitochondrial temperature in surgically resected human tumors is relatively higher than that in paracancerous tissues. Our results indicate that relatively hot mitochondria may exist in tumors from patients. We envisage that our study provides critical evidence for revisiting the Warburg effect and cancer metabolism.

A dual-response fluorescent probe for N2H4 and viscosity in living cells and zebrafish to evaluate liver injury.

Hydrazide drugs can cause severe drug-induced liver injury owing to the enzymatic release of N2H4 in the liver. Also, changes in cellular viscosity are associated with liver damage. Thus, simultaneous monitoring of changes in N2H4 levels and viscosity can be used to evaluate the side effects of hydrazide drugs. Herein, we firstly reported a near-infrared fluorescent probe (FNN), which contains 1,8-naphthalimide as the fluorophore and a chalcone moiety as the responsive receptor, for sensitively detecting intracellular viscosity and N2H4. FNN showed a fast 'turn-on' fluorescence response to N2H4 with excellent selectivity. Additionally, FNN could selectively track viscosity without interference from polarity, pH, and other active species. Furthermore, imaging experiments suggested that FNN could be successfully applied in living cells and zebrafish larvae and embryos, which is of great importance for effectively assessing the degree of liver injury.

A novel dual-functional fluorescent probe for imaging viscosity and cysteine in living system.

Abnormal changes in intracellular viscosity and cysteine are both associated with several important biological processes such as reversible redox reactions, which play a pivotal role in the process of inflammation. However, it remains unclear how cysteine and viscosity are altered in inflammation. Herein, we firstly report a high-sensitivity and -selectivity near-infrared imaging probe (FCV) for tracking intracellular viscosity and endogenous cysteine. This dual-functional probe displays excellent photostability and large Stokes shifts. FCV exhibits a 54-fold enhancement in fluorescence emission at 560 nm with increasing Cys (λex = 420 nm) and an approximately 63-fold enhancement at 660 nm (λex = 460 nm) with increasing viscosity from 1.0 cP to 952.5 cP. Moreover, FCV reveals the synergistic relationship between viscosity and cysteine in the inflammation model of living cells and zebrafish for the first time. Thus, FCV is a promising vehicle to identify the changes in Cys and viscosity in associated diseases.

A bifunctional probe reveals increased viscosity and hydrogen sulfide in zebra fish model of Parkinson's disease.

Altered H2S levels and intracellular viscosity have both been seen in Parkinson's disease (PD). However, how H2S and intracellular viscosity are involved in PD pathogenesis remains unknown. Herein, a dual-function fluorescent probe DF was designed and synthesized to analyze intracellular viscosity and hydrogen sulfide. It is a near-infrared fluorescence probe with improved photostability and large Stokes shift (110 nm). The probe reveals increased viscosity and hydrogen sulfide in zebrafish model of PD for the first time.

A 1,8-naphthalimide-based lysosome-targeting dual-analyte fluorescent probe for the detection of pH and palladium in biological samples.

Fluorescent probes containing 1,8-naphthalimide dyes have been used to detect biomolecules in the environmental and biological fields. However, most of the probes only exhibit single fluorescent output to one analyte, making them insufficient for detection of more analytes. Herein, we developed a novel 1,8-naphthalimide-based lysosome-targeting dual-analyte sensitive fluorescent probe (DPPP) for the detection of pH and palladium (Pd0) using two different emissive channels. The probe showed high selectivity, large Stokes shifts (Δλ ≥ 100 nm) and enhanced response to pH, with blue emission at 485 nm via a morpholine group, and responsive to Pd0 concentration, with yellow emission at 545 nm via an allylcarbamate group. The effect of DPPP was successfully observed for sensitive visualizing pH and Pd0 concentration in the lysosome of HeLa cells and zebrafish using fluorescence microscopy. This work provides guidance for the design of dual-analyte fluorescent probes.

A dual-rotator fluorescent probe for analyzing the viscosity of mitochondria and blood.

A novel mitochondria-targeting molecular rotator FD was designed to visualize changes in viscosity under hypoxic conditions in vitro and in vivo. Importantly, FD can be used to detect changes in the blood viscosity of liver cancer and liver cirrhosis patients, and also rehabilitation of liver disease.

Dual ligand-promoted palladium-catalyzed nondirected C-H alkenylation of aryl ethers.

Direct C-H functionalization of aryl ethers remains challenging owing to their low reactivity and selectivity. Herein, a novel strategy for nondirected C-H alkenylation of aryl ethers promoted by a dual ligand catalyst was demonstrated. This catalytic system readily achieved the highly efficient alkenylation of alkyl aryl ethers (anisole, phenetole, n-propyl phenyl ether, n-butyl phenyl ether and benzyl phenyl ether), cyclic aryl ethers (1,4-benzodioxan, 2,3-dihydrobenzofuran, dibenzofuran), and diphenyl oxides. Moreover, the proposed methodology was successfully employed for the late-stage modification of complex drugs containing the aryl ether motif. Interestingly, the compounds developed herein displayed fluorescent properties, which would facilitate their biological applications.

A highly sensitive red-emitting probe for the detection of viscosity changes in living cells, zebrafish, and human blood samples.

Intracellular viscosity can be measured to reflect the state of living cells. Fluorescent probes are powerful tools for viscosity detection in vivo. Herein, we report on a novel red-emitting viscosity-sensitive probe DJH with a large Stokes shift of 165 nm, showing a 400-fold fluorescence enhancement from PBS solution to 90% glycerol. The probe was suitable for the visualization of the changes in viscosity within living cells and also in zebrafish treated with microplastics for the first time. Furthermore, the viscosity of fresh blood from diabetic mice and hypertensive and diabetic patients was first evaluated by using DJH. These results showed that the probe has a wide range of potential applications in basic research on environmental pollution and in the pre-diagnosis of patients.