A Near-Infrared Fluorescent Probe with Large Stokes Shift for Sensitive Detection of Hydrogen Sulfide in Environmental Water, Food Spoilage, and Biological Systems.

Hydrogen sulfide (H2S) is an important endogenous gas transmitter that plays a critical role in various physiological and pathological processes and can also cause a negative impact on foodstuffs. In this study, we designed and synthesized a simple, easily available, high-yield, and low-cost near-infrared (λem = 710 nm) fluorescent probe, DEM-H2S, with a substantial Stokes shift (205 nm) for the detection of H2S. DEM-H2S features high selectivity and sensitivity (LOD = 80 nM) toward H2S, accompanied by a noticeable color change. Upon interaction with H2S, DEM-H2S exhibits a restored ICT (Intramolecular Charge Transfer) process, thereby manifesting near-infrared fluorescence. DEM-H2S has been successfully utilized to detect H2S in actual water samples and to monitor the spoilage of food items, such as pork, shrimp, and eggs. Furthermore, DEM-H2S enables the imaging of endogenous and exogenous H2S in living MCF-7 cells and zebrafish. Hence, DEM-H2S provides an attractive method for the detection of H2S in environmental, food, and biological systems, holding potential value in physiological and pathological research.

Monitoring the Mitochondrial Viscosity Changes During Cuproptosis with Iridium(III) Complex Probe via In Situ Phosphorescence Lifetime Imaging.

Cuproptosis is a novel copper-dependent form of programmed cell death, displaying important regulatory functions in many human diseases, including cancer. However, the relationship between the changes in mitochondrial viscosity, a key factor associated with cellular malfunction, and cuproptosis is still unclear. Herein, we prepared a phosphorescent iridium (Ir) complex probe for precisely monitoring the changes of mitochondrial viscosity during cuprotosis via phosphorescence lifetime imaging. The Ir complex probe possessed microsecond lifetimes (up to 1 µs), which could be easily distinguished from cellular autofluorescence to improve the imaging contrast and sensitivity. Benefiting from the long phosphorescence lifetime, excellent viscosity selectivity, and mitochondrial targeting abilities, the Ir complex probe could monitor the increase in the mitochondrial viscosity during cuproptosis (from 46.8 to 68.9 cP) in a quantitative manner. Moreover, through in situ fluorescence imaging, the Ir complex probe successfully monitored the increase in viscosity in zebrafish treated with lipopolysaccharides or elescolomol-Cu2+, which were well-known cuproptosis inducers. We anticipate that this new Ir complex probe will be a useful tool for in-depth understanding of the biological effects of mitochondrial viscosity during cuproptosis.

Eco-friendly photothermal hydrogel evaporator for efficient solar-driven water purification.

The field of solar vapor generation has developed rapidly in recent years, but achieving the goals of a high evaporation rate, eco-friendliness and rapid preparation with low-cost raw materials is still a challenge. In this work, a type of photothermal hydrogel evaporator was prepared by blending eco-friendly poly(vinyl alcohol), agarose, Fe3+ and tannic acid (TA) together, in which the tannic acid-ferric ion (TA*Fe3+) complexes served as photothermal materials and effective gelators. The results indicate that the TA*Fe3+ complex exhibits excellent gelatinization ability and light-absorption performance, which leads to a compressive stress of 0.98 MPa at 80% strain and up to 85% light absorption ratio in the photothermal hydrogel. For interfacial evaporation, a high rate of 1.897 ± 0.11 kg·m-2·h-1 corresponding to an energy efficiency of 89.7 ± 2.73% under 1 sun irradiation is achieved. Moreover, the hydrogel evaporator exhibits high stability in a 12-hour test and a 20-cycle test without a decline in evaporation performance. The outdoor testing results show that the hydrogel evaporator can achieve an evaporation rate of > 0.70 kg/m2 and effectively purify wastewater treatment and seawater desalination.

Design, Synthesis, Antifungal Activity, and Molecular Docking of Streptochlorin Derivatives Containing the Nitrile Group.

Based on the structures of natural products streptochlorin and pimprinine derived from marine or soil microorganisms, a series of streptochlorin derivatives containing the nitrile group were designed and synthesized through acylation and oxidative annulation. Evaluation for antifungal activity showed that compound 3a could be regarded as the most promising candidate-it demonstrated over 85% growth inhibition against Botrytis cinerea, Gibberella zeae, and Colletotrichum lagenarium, as well as a broad antifungal spectrum in primary screening at the concentration of 50 µg/mL. The SAR study revealed that non-substituent or alkyl substituent at the 2-position of oxazole ring were favorable for antifungal activity, while aryl and monosubstituted aryl were detrimental to activity. Molecular docking models indicated that 3a formed hydrogen bonds and hydrophobic interactions with Leucyl-tRNA Synthetase, offering a perspective for the possible mechanism of action for antifungal activity of the target compounds.

Visual and Rapid Detection of Nerve Agent Mimics in Gas and Solution Phase by a Simple Fluorescent Probe.

Chemical nerve agents are highly toxic organophosphorus compounds that are easy to obtain and can be utilized by terrorists to threaten homeland security and human safety. Those organophosphorus nerve agents contain nucleophilic ability that can react with acetylcholinesterase leading to muscular paralysis and human death. Therefore, there is great importance to explore a reliable and simple method to detect chemical nerve agents. Herein, the o-phenylenediamine-linked dansyl chloride as a colorimetric and fluorescent probe has been prepared to detect specific chemical nerve agent stimulants in the solution and vapor phase. The o-phenylenediamine unit serves as a detection site that can react with diethyl chlorophosphate (DCP) in a rapid response within 2 min. A satisfied relationship line was obtained between fluorescent intensity and the concentration of DCP in the range of 0-90 µM. In the optimized conditions, we conducted the fluorescent titration to measure the limits of detection (0.082 µM) with the fluorescent enhancement up to 18-fold. Fluorescence titration and NMR studies were also conducted to explore the detection mechanism, indicating that the formation of phosphate ester causes the intensity of fluorescent change during the PET process. Finally, probe 1 coated with the paper test is utilized to detect DCP vapor and solution by the naked eye. We expect that this probe may give some admiration to design the small molecule organic probe and applied in the selectivity detection of chemical nerve agents.

Design, synthesis, antifungal activity and molecular docking of ring-opened pimprinine derivative containing (thio)amide structure.

BACKGROUND: To obtain new environmentally friendly fungicides, we used the natural product pimprinine as the lead compound, and designed and synthesized two series of ring-opening derivatives of pimprinine containing amide/thioamide. We then studied their antifungal activity against six common plant pathogenic fungi in vitro. RESULTS: Most of the target compounds have good antifungal activity against six important plant pathogenic fungi in vitro. At a concentration of 50 µg ml-1 , compound 3o showed prominent antifungal effects on Alternaria solani and Rhioctornia solani, with inhibition rates of 91.8% and 97.4%, and a 50% effective concentration (EC50 ) of 6.2255 and 0.6969 µg ml-1 respectively. The EC50 of compound 3o against Alternaria solani was significantly lower than that of boscalid (13.0380 µg ml-1 ) and flutriafol (11.9057 µg ml-1 ). In addition, compound 3o had good antifungal activity against Sclerotinia sclerotiorum, cucumber powdery mildew, cucumber Botrytis cinerea and Phytophthora capsici in vivo; the antifungal activity of compound 3o against cucumber Botrytis cinerea is 91.7%. At the same time, docking results for highly active compound 3o with the presumed target succinate dehydrogenase and the molecular docking prediction scores of all compounds further indicate its possible antifungal activity mechanism. CONCLUSION: The designed and optimized derivative 3o of ring-opening pimprinine has good antifungal activity and can be used as a new antifungal drug for further research. © 2023 Society of Chemical Industry.

An H2S-Regulated Artificial Nanochannel Fabricated by a Supramolecular Coordination Strategy.

Hydrogen sulfide (H2S), as the third gasotransmitter, has an important impact on physiological and pathological activities. Herein, we fabricated an artificial nanochannel with a conductance value of 2.01 nS via a supramolecular coordination strategy. Benefiting from the unique H2S-mediated covalent reaction, the nanochannel biosensor could change from ON to OFF states with the addition of H2S. Furthermore, this nanochannel directed the ion transport, showing a high rectification ratio as well as gating ratio. Subsequently, theoretical simulations were conducted to help to reveal the possible mechanism of the functionalized nanochannel. This study can provide insights for better understanding the process of H2S-regulated biological channels and fabricating gas gated nanofluids.

Rapid Fabrication of Porous Photothermal Hydrogel Coating for Efficient Solar-Driven Water Purification.

Cost management and scalable fabrication without sacrificing the purification performance are two critical issues that should be addressed before the practical commercial application of solar-driven evaporators. To address this challenge, we report a porous photothermal hydrogel coating prepared by mixing the raw materials of sawdust (SD), carbon nanotubes (CNTs), and poly(vinyl alcohol) (PVA), which was applied to undergo a blading-drying-rehydration process to prepare the evaporator. In the coating, the crystallized PVA gives the coating a solid skeleton and the sawdust endows the coating with a loose structure to sufficiently enhance the water transportation capacity. As a result, the evaporator coated with the hydrogel coating displays a high water transport rate and efficient evaporation performance along with excellent mechanical properties and stability. Water migrates vertically upward 5 cm within 4 minutes. The compressive stress of the rehydrated hydrogel coating reaches as high as 14.28 MPa under 80% strain. The water evaporation rate of the hydrogel coating-based evaporator reaches 1.833 kg m-2 h-1 corresponding to an energy efficiency of 83.29% under 1 sun irradiation. What is more, the hydrogel coating retains its excellent evaporation performance and stability after immersion in acid or alkali solution, ultrasound treatment, and long-time immersion in water. Under outdoor conditions, the water evaporation rate of the hydrogel coating-based evaporator is about 5.69 times higher than that of pure water. This study proposes a rapid, cost-effective, and scalable strategy for preparing a high-performance photothermal hydrogel coating that will find sustainable and practical application in solar-driven water purification.

Structure-Guided Discovery of the Novel Covalent Allosteric Site and Covalent Inhibitors of Fructose-1,6-Bisphosphate Aldolase to Overcome the Azole Resistance of Candidiasis.

Fructose-1,6-bisphosphate aldolase (FBA) represents an attractive new antifungal target. Here, we employed a structure-based optimization strategy to discover a novel covalent binding site (C292 site) and the first-in-class covalent allosteric inhibitors of FBA from Candida albicans (CaFBA). Site-directed mutagenesis, liquid chromatography-mass spectrometry, and the crystallographic structures of APO-CaFBA, CaFBA-G3P, and C157S-2a4 revealed that S268 is an essential pharmacophore for the catalytic activity of CaFBA, and L288 is an allosteric regulation switch for CaFBA. Furthermore, most of the CaFBA covalent inhibitors exhibited good inhibitory activity against azole-resistant C. albicans, and compound 2a11 can inhibit the growth of azole-resistant strains 103 with the MIC80 of 1 µg/mL. Collectively, this work identifies a new covalent allosteric site of CaFBA and discovers the first generation of covalent inhibitors for fungal FBA with potent inhibitory activity against resistant fungi, establishing a structural foundation and providing a promising strategy for the design of potent antifungal drugs.

Synthesis and Discovery of Schiff Base Bearing Furopyrimidinone for Selective Recognition of Zn2+ and its Applications in Cell Imaging and Detection of Cu2.

A simplefuro [2,3-d]pyrimidinone-based Schiff base FPS was synthesized via aza-Wittig reaction and structure elucidation was carried out by spectroscopic studies FT-IR, 1H NMR, and 13C NMR and mass spectrometry. FPS showed weak fluorescence emission in methanol and the selectivity of FPS to different metal ions (Mn2+, Ca2+, Fe2+, Fe3+, Mg2+, Al3+, Ba2+, Ag+, Co2+, Na+, K+, Cu2+, Zn2+, Pb2+, Bi3+) were studied by absorption and fluorescence titration. The results show that FPS has selective fluorescence sensing behavior for Zn2+ ions and the limit of detection (LOD) was calculated to be 1.19 × 10-8 mol/L. Moreover, FPS-Zn2+ acts as a metal based highly selective and sensitive new chemosensor for Cu2+ ions and the LOD was calculated to be 2.25 × 10-7 mol/L. In accordance with the results and theoretical calculations, we suspected that the binding mechanisms of FPS to Zn2+ and Cu2+ were assigned to be the cooperative interaction of Zn2+(Cu2+)-N.

Vinylation of α-Aminoazoles with Triethylamine: A General Strategy to Construct Azolo[1,5-a]pyrimidines with a Nonsubstituted Ethylidene Fragment.

A new general synthesis of pharmaceutically important azolo[1,5-a]pyrimidines starting from widely available 3(5)-aminoazoles, aldehydes, and triethylamine is developed. The key is to enable the vinylation reaction that allows the in situ generation of elusive acyclic enamines and the subsequent annulation reaction to occur. This direct and practical strategy is capable of constructing a range of 5,6-unsubstituted pyrazolo[1,5-a]pyrimidines and [1,2,4]triazolo[1,5-a]pyrimidines. More importantly, this protocol provides a concise synthetic route to prepare the clinically used zaleplon.

Streptochlorin analogues as potential antifungal agents: Design, synthesis, antifungal activity and molecular docking study.

Streptochlorin is a small molecule of indole alkaloid isolated from marine Streptomyces sp., it is a promising lead compound due to its potent bioactivity in preventing many phytopathogens in our previous study, but further structural modifications are required to improve its antifungal activity. Our work in this paper focused on the replacement of oxazole ring in streptochlorin with the imidazole ring, to discover novel analogues. Based on this design strategy, three series of streptochlorin analogues were efficiently synthesized through sequential Vilsmeier-Haack reaction, Van Leusen imidazole synthesis and halogenation reaction. Some of the analogues displayed excellent activity in the primary assays, and this is highlighted by compounds 4g and 4i, the growth inhibition against Alternaria Leaf Spot and Rhizoctorzia solani under 50 µg/mL are 97.5% and 90.3%, respectively, even more active than those of streptochlorin, pimprinine and Osthole. Molecular docking models indicated that streptochlorin binds with Thermus thermophiles Leucyl-tRNA Synthetase in a similar mode to AN2690, offering a perspective on the mode of action study for antifungal activities of streptochlorin derivatives. Further study is still ongoing with the aim of discovering synthetic analogues, with improved antifungal activity and clear mode of action.

Diversity-oriented synthesis and antifungal activities of novel pimprinine derivative bearing a 1,3,4-oxadiazole-5-thioether moiety.

Based on the strategy of diversity-oriented synthesis and the structures of natural product pimprinine and streptochlorin, two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties were efficiently synthesized under the optimized reaction conditions. Biological assays conducted at Syngenta showed the designed derivatives displayed an altered pattern of biological activity, of which 5h was identified as the most promising compound with strong activity against Pythium dissimile and also a broad antifungal spectrum in primary screening. Further structural optimization of pimprinine and streptochlorin derivatives is well under way, aiming to discover synthetic analogues with improved antifungal activity. Two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties were efficiently synthesized through diversity-oriented synthesis strategy under the optimized conditions. Biological assays showed the designed derivatives exhibited potential activity.

Biological evaluation and SAR analysis of novel covalent inhibitors against fructose-1,6-bisphosphatase.

Fructose-1,6-bisphosphatase (FBPase) is an attractive target for affecting the GNG pathway. In our previous study, the C128 site of FBPase has been identified as a new allosteric site, where several nitrovinyl compounds can bind to inhibit FBPase activity. Herein, a series of nitrostyrene derivatives were further synthesized, and their inhibitory activities against FBPase were investigated in vitro. Most of the prepared nitrostyrene compounds exhibit potent FBPase inhibition (IC50 < 10 µM). Specifically, when the substituents of F, Cl, OCH3, CF3, OH, COOH, or 2-nitrovinyl were installed at the R2 (meta-) position of the benzene ring, the FBPase inhibitory activities of the resulting compounds increased 4.5-55 folds compared to those compounds with the same groups at the R1 (para-) position. In addition, the preferred substituents at the R3 position were Cl or Br, thus compound HS36 exhibited the most potent inhibitory activity (IC50 = 0.15 µM). The molecular docking and site-directed mutation suggest that C128 and N125 are essential for the binding of HS36 and FBPase, which is consistent with the C128-N125-S123 allosteric inhibition mechanism. The reaction enthalpy calculations show that the order of the reactions of compounds with thiol groups at the R3 position is Cl > H > CH3. CoMSIA analysis is consistent with our proposed binding mode. The effect of compounds HS12 and HS36 on glucose production in primary mouse hepatocytes were further evaluated, showing that the inhibition was 71% and 41% at 100 µM, respectively.

A Multi-responsive Fluorescent Probe Reveals Mitochondrial Nucleoprotein Dynamics with Reactive Oxygen Species Regulation through Super-resolution Imaging.

Understanding the biomolecular interactions in a specific organelle has been a long-standing challenge because it requires super-resolution imaging to resolve the spatial locations and dynamic interactions of multiple biomacromolecules. Two key difficulties are the scarcity of suitable probes for super-resolution nanoscopy and the complications that arise from the use of multiple probes. Herein, we report a quinolinium derivative probe that is selectively enriched in mitochondria and switches on in three different fluorescence modes in response to hydrogen peroxide (H2 O2 ), proteins, and nucleic acids, enabling the visualization of mitochondrial nucleoprotein dynamics. STED nanoscopy reveals that the proteins localize at mitochondrial cristae and largely fuse with nucleic acids to form nucleoproteins, whereas increasing H2 O2 level leads to disassociation of nucleic acid-protein complexes.

A colorimetric and fluorescence turn-on probe for the detection of palladium in aqueous solution and its application in vitro and in vivo.

Palladium has attracted a growing number of attention due to its widely application and environmental toxicity. Consequently, a novel colorimetric and fluorescent turn-on probe (NT-Pd) was designed for sensing of palladium. This probe was capable of detecting palladium in aqueous solution (DMSO was less than 1%, v/v). Under this mild condition, NT-Pd displayed high selectivity and sensitivity for sensing of palladium in both colorimetric and fluorescent strategy, such as low detection limit (5.30 nM) and rapid response time (within 10 min). In addition, NT-Pd was successfully applied for imaging of exogenous palladium in living cells and zebrafishes with good biocompatibility and low toxicity, indicating this probe has satisfactory application potential to track palladium in the complicated biological system.

Multifunctional Mineral Hydrogels: Potential in Artificially Intelligent Skins and Drug Delivery.

Hydrogels have received considerable attention due to their potential applications in the fields of drug delivery, tissue engineering, and stimuli-responsive devices. Nonetheless, it is still a great difficulty in designing hydrogels with multifunctional characteristics including excellent antibacterial activity and appropriate mechanical and remarkable sensing properties. In the present study, a novel type of organic-inorganic adhesive is demonstrated, which comprises inorganic matter of amorphous calcium phosphate particles and organic substances of poly(acrylic acid) and chitosan. The hydrogel possesses excellent biocompatible and antibacterial activity, unique viscoelastic properties, high quantity of drug load, and remarkably sensitive pressure sensing, which have potential use as antibacterial biomaterials, artificially intelligent skins, and drug delivery carriers.

Discovery of novel allosteric site and covalent inhibitors of FBPase with potent hypoglycemic effects.

Fructose-1,6-bisphosphatase (FBPase) is an essential enzyme of GNG pathway. Significant advances demonstrate the FBPase plays a critical role in treatment of diabetes. Numerous FBPase inhibitors were developed by targeting AMP site, nevertheless, none of these inhibitors has exhibited suitable potency and druggability. Herein, a new allosteric site (C128) on FBPase was discovered, and several nitrostyrene compounds exhibiting potent FBPase inhibitions were found covalently bind to C128 site on FBPase. Mutagenesis suggest that C128 is the only cysteine that can influence FBPase inhibition, the N125-S124-S123 pathway was most likely involved in allosteric signaling transmission between C128 and active site. However, these nitrostyrenes may bind with multiple cysteine besides C128 in FBPase. To improve pocket selectivity, a series of novel compounds (14a-14n) were re-designed rationally by integrating fragment-based covalent virtual screening and machine-learning-based synthetic complexity evaluation. As expected, the mass spectrometry validated that the proportion of title compounds binding to the C128 in FBPase was significantly higher than that of nitrostyrenes. Notably, under physiological and pathological conditions, the treatment of compounds 14b, 14c, 14i or 14n led to potent inhibition of glucose production, as well as decreased triglyceride and total cholesterol levels in mouse primary hepatocytes. We highlight a novel paradigm that molecular targeting C128 site on FBPase can have potent hypoglycemic effect.

Aerobic α,ß-C(sp3)-H Bond Difunctionalization and C-N Bond Cleavage of Triethylamine: Difunctional Ammonium Iodide Enabling the Regioselective Synthesis of 4-Arylpyrimido[1,2-b]indazoles.

A novel method for the regioselective synthesis of 4-arylpyrimido[1,2-b]indazoles has been developed via the dual C(sp3)-H bond functionalization and C-N bond cleavage of triethylamine. The elusive acyclic enamine intermediates are effectively in situ generated and captured by aromatic aldehydes to form a wide array of tricyclic products from 3-aminoindazoles under the NH4I-mediated aerobic oxidative conditions. This reaction features easily available feedstock, green and economic conditions, and valuable products.

Nanostructures assembly and the property of polysaccharide extracted from Tremella Fuciformis fruiting body.

Polysaccharides from fungi are good free radical scavengers. However, there are no enzymes digesting these polysaccharides in the human body, which limits the use of fungal polysaccharides. Therefore, it is of great significance to study the preparation methods of fungal polysaccharides to improve the utilization rate of fungal polysaccharides. In this paper, the acidic polysaccharide of Tremella fuciformis was extracted by boiling and precipitated by ethanol. The total sugar content obtained by freeze-drying after ion exchange chromatography purification was 93.6%. It is mainly composed of mannose, glucuronic acid, xylose and fucose. According to the peak area, the mass ratio of the substance is about 6.8:1:1.5:0.6, which indicates that TFP is a polysaccharide with mannose as its main chain and glucuronic acid, fucose and xylose as well as a small amount of glucose as the branch chain. Molecular weight is 1.86 × 106 Da. The existence of glucuronic acid endows polysaccharides with negative charge in aqueous solution and can be assembled into nanostructures with chitosan. By measuring the swelling property in aqueous, it shows the TFP separated from Tremella fuciformis fruits is suitable for drug controlled release.