Integrating a Copper-Histidine Brace in a Mimetic Nanozyme Streamlines the Tyrosinase Recognition Moiety to Achieve Chiral Differentiation.

Designing artificial mimetic enzymes with high activity/selectivity to replace chiral bioenzymes is of great interest in the development of chiral materials consisting of molecules, enantiomers, that exist in two forms as mirror images of one another but cannot be superimposed. In this study, the chiral catalytic structural unit was streamlined from tyrosinase to integrate a mimetic nanozyme. The chiral amino acid l-histidine, as the chiral binding/recognition site, and the active metal site Cu were coupled (Cu@l-His) to create a copper-histidine brace with enantioselective catalytic ability to tyrosinol enantiomers. Results of kinetic parameters and activation energies confirmed the excellent peroxidase-like activity with a preference of Cu@l-His to l-tyrosinol. Such a preference could be attributed to the structurally oriented copper-histidine brace with a stronger affinity and catalytic activity to l-tyrosinol. By accurately evaluating chiral recognition units derived from bioenzymes, stable and superior chiral mimetic nanoenzymes could be constructed in a more straightforward and simplified manner, and they could also be extended to the reconstruction of diverse chiral enzymes.

Twisted Intramolecular Charge Transfer-Based Viscosity-Responsive Probe Reveals Lysosomal Degradation Process of Endocytosed Foreign Bodies.

The optimization of nanomedicines requires a thorough understanding of nanocarrier attrition during lysosome-mediated biological processes. Real-time monitoring of endocytosis provides valuable insights into the lysosomal effects on nanocarriers and the release of nanodrugs. We report the development of a coresponsive probe that detects changes in the spatial viscosity of the intracellular domain caused by lysosomal degradation of foreign bodies. The probe, based on a benzofuro[2,3-d]pyrimidine structure, exhibits torsional intramolecular charge transfer (TICT) and responds to ambient viscosity changes with a sensitive fluorescence intensity. The antidiffused fluorescence transition of the probe in the spatially restricted domain serves as a key indicator for real-time monitoring. When encapsulated with diverse foreign bodies and emitted into macrophages by endocytosis, the probe forms nanoparticles. Lysosomes uptake these materials for intracellular digestion, causing alterations in the aggregation or depolymerization state of the nanoparticles, leading to viscosity changes manifested by the probe's fluorescence. By studying the spatial viscosity changes caused by lysosomal degradation of foreign bodies, our monitoring strategy contributes to understanding the digestion or escape capabilities of potential pharmaceutical-carrying nanocarriers, providing guidelines to design more effective nanocarriers that navigate lysosomal degradation to achieve precise drug payloads and release.

Tandem Four-Component Reaction to Access Fused Polycycles Exhibiting Aggregation-Enhanced Through-Space Charge Transfer Emission.

Rapid construction of new fluorescence emitters is essential in advancing synthetic luminescent materials. This study illustrated a piperidine-promoted reaction of chiral dialdehyde with benzoylacetonitrile and malonitrile, leading to the formation of the 6/6/7 fused cyclic product in good yield. The proposed reaction mechanism involves a dual condensation/cyclization process, achieving the formation of up to six bonds for fused polycycles. The single crystal structure analysis revealed that the fused cyclic skeleton contains face-to-face naphthyl and cyanoalkenyl motifs, which act as the electronic donor and acceptor, respectively, potentially resulting in through-space charge transfer (TSCT) emission. While the TSCT emissions were weak in solution, a notable increase in luminescence intensity was observed upon aggregation, indicating bright fluorescent light. A series of theoretical analyses further supported the possibility of spatial electronic communication based on frontier molecular orbitals, the distance of charge transfer, and reduced density gradient analysis. This work not only provides guidance for the one-step synthesis of complex polycycles, but also offers valuable insights into the design of aggregation-enhanced TSCT emission materials.

Gold Nanoclusters Whose Photoluminescent Properties are Dynamically Tunable by Modulating the Assembly Pathway Complexity.

Modulating the assembly pathway is an indispensable strategy for optimizing the performance of optical materials. However, implementing this strategy is nontrivial for metal nanocluster building blocks, due to the limited functional modification of nanoclusters and complexity of their emission mechanism. In this report, we demonstrate that a gold nanocluster modified by 4,6-diamino-2-pyrimidinethiol (DPT-AuNCs) self-assembles into two distinct aggregation structures in methanol (MeOH)/water mixed solvent, thus exhibiting pathway complexity. Kinetic studies show that DPT-AuNCs firstly assembles into non-luminescent nanofibers (kinetically controlled), which further transforms into strongly luminescent microflowers (thermodynamically controlled). In-depth analysis of the assembly mechanism reveals that the transformation of aggregation structures involves the disassembly of nanofibers and a subsequent nucleation-growth process. Temperature-dependent photoluminescence (PL) spectroscopy and infrared (IR) measurements reveal that inter-cluster hydrogen bonding bridged by solvent molecules and C-H⋅⋅⋅π interaction are the key factors for emission enhancement. The photoluminescent property of DPT-AuNCs can be controlled by varying the cosolvent in water, enabling DPT-AuNCs to distinguish different kind of alcohols, particularly the isomerism n-propanol (NPA) and isopropanol (IPA). Additionally, the addition of seeds effectively regulate the assembly kinetics of DPT-AuNCs. This study advances our understanding of assembly pathways and improves the luminescent performance of nanoclusters (NCs).

Spatially confined dual-emission nanoprobes assembled from silicon nanoparticles and gold nanoclusters for ratiometric biosensing.

Gold nanoclusters (AuNCs) possess weak intrinsic fluorescence, limiting their sensitivity in biosensing applications. This study addresses these limitations by developing a spatially confined dual-emission nanoprobe composed of silicon nanoparticles (SiNPs) and AuNCs. This amplified and stabilized fluorescence mechanism overcomes the limitations associated with using AuNCs alone, achieving superior sensitivity in the sensing platform. The nanoprobe was successfully employed for ratiometric detection of bleomycin (BLM) in serum samples, operating at an excitation wavelength of 365 nm, with emission wavelengths at 480 nm and 580 nm. The analytical performance of the system is distinguished by a linear detection range of 0-3.5 µM, an impressive limit of detection (LOD) of 35.27 nM, and exceptional recoveries ranging from 96.80 to 105.9%. This innovative approach significantly enhances the applicability and reliability of AuNC-based biosensing in complex biological media, highlighting its superior analytical capabilities.

Relay Copper-Catalyzed Synthesis of Imidazo[1,5-a]pyridine Scaffolds from Phenylalanine and Halohydrocarbon.

An efficient and straightforward strategy to synthesize imidazo[1,5-a]pyridine compounds from phenylalanine and halohydrocarbon has been successfully developed. The protocol features a relay copper-catalyzed reaction involving intermolecular C-O coupling and intramolecular C-N cyclization, providing an approach to access a diverse range of imidazo[1,5-a]pyridine derivatives with unique aza quaternary carbon centers.

Late-Stage Diversification of Peptides via Pd-Catalyzed Site-Selective δ-C(sp2)-H Fluorination and Amination.

Site-selective C-H fluorination is an attractive strategy for directly transforming inert C-H bonds into C-F bonds, yet it remains a significant challenge. Herein, we have developed an efficient and versatile strategy for site-selective fluorination and amination of phenylalanine-containing peptides via late-stage Pd-catalyzed δ-C(sp2)-H activation, providing a valuable tool for the in situ synthesis of fluorinated indoline scaffolds within peptides.

Copper-Catalyzed Chemodivergent Synthesis of Oxazoles and Imidazolidones by Selective C-O/C-N Cyclization.

Efficient synthesis of phenylalanine-derived oxazoles and imidazolidones can be achieved by copper-catalyzed reactions that are controlled by directing groups and proceed by selective C-O or C-N coupling. This strategy employs inexpensive commercial copper catalysts and readily available starting materials. It uses a convenient reaction procedure and provides a reliable approach to the versatile and flexible assembly of heterocyclic building blocks.

Biomass-involved synthesis of N-substituted benzofuro[2,3-d]pyrimidine-4-amines and biological evaluation as novel EGFR tyrosine kinase inhibitors.

Shikimic acid (1) is a renewable biomass which could be obtained sustainably through natural product isolation or metabolic engineering. Owing to its great potential in chemical conversion, the value-added utilization of this non-grain biomass has received much attention in recent years. Based on the established transformation route from shikimic acid (1) to methyl 3-dehydroshikimate (3-MDHS, 2) and to the multi-functionalized methyl 2-amino-3-cyanobenzofuran-5-carboxylate (3), we disclose a facile and transition metal-free method to access a series of N-substituted benzofuro[2,3-d]pyrimidine-4-amines in 63%-90% yields. The identification of these compounds as EGFR tyrosine kinase inhibitors has also been described. Among them, compound 5h exhibited the most potent inhibitory effect against EGFR tyrosine kinase with an IC50 of 1.7 nM and excellent antiproliferative activity against A431 and A549 cell lines with a GI50 of 5.1 and 12.3 µM, respectively.

The Structure-Activity Relationship of Pterostilbene Against Candida albicans Biofilms.

Candida albicans biofilms contribute to invasive infections and dramatic drug resistance, and anti-biofilm agents are urgently needed in the clinic. Pterostilbene (PTE) is a natural plant product with potentials to be developed as an anti-biofilm agent. In this study, we evaluated the structure-activity relationship (SAR) of PTE analogues against C. albicans biofilms. XTT (Sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt) reduction assay was used to evaluate the activity of the analogues against C. albicans biofilms. Knowing that hyphal formation is essential for C. albicans biofilms, anti-hyphal assay was further carried out. By comparing a series of compounds tested in this study, we found that compounds with para-hydroxy (-OH) in partition A exhibited better activity than those with other substituents in the para position, and the double bond in partition B and meta-dimethoxy (-OCH3) in partition C both contributed to the best activity. Consistent results were obtained by anti-hyphal assay. Collectively, para-hydroxy (-OH), double bond and meta-dimethoxy (-OCH3) are all needed for the best activity of PTE against C. albicans biofilms.

Synthesis of Coumestrol and Aureol.

A total synthesis of coumestrol (1) and aureol (2) is described. The Perkin condensation of 2-bromo-4-hydroxylphenylacetic acid (6) and o-hydroxybenzaldehydes (7) gave the corresponding 2'-bromo-3-arylcoumarins (9). A copper-catalyzed consecutive hydroxylation and aerobic oxidative coupling of 9 under microwave conditions facilitated the total synthesis of 1 and 2, respectively, with spectroscopic data highly similar to those of natural products.

Cu-Catalyzed Consecutive Hydroxylation and Aerobic Oxidative Cycloetherification under Microwave Conditions: Entry to 2-Arylbenzofuran-3-carboxylic Acids.

A convenient one-pot synthesis of 2-arylbenzofuran-3-carboxylic acids from (E)-2-(2-bromophenyl)-3-phenylacrylic acids via Cu-catalyzed consecutive hydroxylation and aerobic oxidative cycloetherification under microwave conditions has been developed. This protocol employed the reagent combination of Cu(OAc)2, 1,10-phen, and KOH in DMSO/H2O (1:1), all of which are cost-effective, readily available, and easily removable from the reaction mixture. Utilizing this synthetic protocol, various 2-arylbenzofuran-3-carboxylic acids as well as the natural product moracin M have been synthesized in satisfactory yields under mild conditions.

Backbone-Enabled and Ester Groups Switched δ-C(sp2)-H Amination/Fluorination: Cyclic Dipeptides Synthesis.

An efficient and concise strategy for the synthesis of cyclic dipeptides via Pd-catalyzed site-selective δ-C(sp2)-H amination/fluorination and N-to-C cyclization is disclosed. The backbone amides within the dipeptides serves as endogenous directing groups, while the desired products were switched by the C-terminal ester group. This chemistry presents a novel and robust alternative to construct cyclodipeptide fragments.

Late-Stage Modification of Peptides with Maleimides through Palladium-Catalyzed ß-C(sp3)-H Alkylation.

Transition-metal-catalyzed C-H activation has proven to be a powerful tool for the late-stage modification of peptides. We herein report a method for site-selective alkylation of peptides with maleimides through Pd-catalyzed ß-C(sp3)-H activation. In this protocol, the methionine residues within peptides serve as the directing groups, which circumvented the preinstallation and subsequent removal of the directing groups. This chemistry exhibited broad substrate scope and can be utilized for peptide ligation.

A dual-emission fluorescent probe with independent polarity and viscosity responses: The synthesis, spectroscopy and bio-imaging applications.

Viscosity and polarity are essential parameters that play critical roles in various physiological processes. Thus, dual-emission fluorescent probes that respond to both polarity and viscosity are highly sought-after tools for studying these processes. In addressing this need, a novel fluorescent probe (L), with dual emissions centered at 460 nm and 780 nm, which can sensitively respond to polarity and viscosity respectively, has been developed. Probe (L) is constructed through rational molecular design, utilizing two conjugated synthons connected by a π-bond to form a D-π-A system. The twisted intramolecular charge transfer (TICT) state is dominant in low-viscosity environments, resulting in weak near-infrared (NIR) fluorescence. Conversely, the intramolecular charge transfer (ICT) state is expected to prevail in high-viscosity environments, leading to strong NIR fluorescence. The polarity-sensitive fluorescence centered at 460 nm can be attributed to the emission of the coumarin unit. Moreover, probe (L) exhibits low cytotoxicity and primarily targets mitochondria. By leveraging the dual-emission properties of probe (L), real-time imaging of polarity and viscosity fluctuations within cells has been achieved. Additionally, probe (L) can be used for in situ and in vivo imaging of rheumatoid arthritis (RA) with good imaging resolution.

Rationally design a novel Zn-MOF for fluorescent detection of nitrofuran antibiotics: The synthesis, structure and sensing applications.

Nitrofuran antibiotics (NFAs) residues in waterare a persistent concern for the public due to the potential threats they pose to human health and the environment. Therefore, efficient probes that are capable of detecting trace amounts of antibiotics in real water environments have become a top priority. Herein, a novel fluorescent Zn-MOF probe (MOF-1) was revealed for the highly selective and sensitive sensing of NFAs. MOF-1 was rationally constructed with Zn(NO3)2·6H2O, 5,5'-(anthracene-9,10-diyl) diisophthalic acid (H4ADIP) and 1,3-bis(imidazol-1-ylmethyl)-benzene (mbib) by using the solvothermal method. Fluorescence sensing experiments demonstrate that MOF-1 can function as a fluorescent sensor for selective, sensitive, and rapid detection of NFAs among 15 antibiotics including ciprofloxacin (CPFX), chloramphenicol (CAP), sulfonamides and NFAs. Fluorescence titration experiments indicated that MOF-1 exhibited remarkably low detection limits of 0.19 µM, 0.26 µM, and 0.34 µM for furazolidone (FZD), furaltadone (FDH) and nitrofurazone (NFZ), respectively. Meanwhile, MOF-1 was successfully employed for NFAs detection in real samples with the recoveries of 98.7 % - 104.1 %, and a relative standard deviation below 5.1 %. Moreover, the sensing mechanism could be ascribed to the synergistic effect between the internal filtering effect and photoinduced electron transfer according to the experiment results and DFT calculations. Additionally, test strips were prepared based on MOF-1 for point of care testing of NFAs.

Backbone-enabled modification of peptides with benzoquinone via palladium-catalyzed δ-C(sp2)-H functionalization.

Backbone-enabled site-selective modification of peptides with benzoquinone via Pd-catalyzed δ-C(sp2)-H functionalization has been achieved. The amide groups of peptides serve as internal directional groups, facilitating C-H functionalization through a kinetically less favored six-membered palladacycle. This methodology presents novel opportunities for the late-stage site-selective diversification of peptides.

Highly efficient removal and real-time visual detection of fluoride ions using ratiometric CAU-10-NH2@RhB: Probe design, sensing performance, and practical applications.

The extensive use of fluoride in agriculture, industry, medicine, and daily necessities has raised growing concerns about fluoride residue. To date, real-time visual detection and efficient removal of fluoride ions from water remain greatly desirable. Herein, nano-CAU-10-NH2@RhB is introduced as a ratiometric fluorescent probe and efficient scavenger for the intelligent detection and removal of fluoride ions. CAU-10-NH2@RhB is readily obtained through one-pot synthesis and exhibits high sensitivity and selectivity for real-time fluoride ion detection, with a naked-eye distinguishable color change from pink to blue. A portable device for point-of-care testing was developed based on color hue analysis readout using a smartphone. A quantitative response was achieved across a wide concentration range, with a detection limit of 54.2 nM. Adsorption experiments suggest that nano-CAU-10-NH2@RhB serves as an efficient fluoride ion scavenger, with a fluoride adsorption capacity of 49.3 mg/g. Moreover, the mechanistic study revealed that hydrogen bonds formed between fluoride ions and amino groups of CAU-10-NH2@RhB are crucial for the detection and adsorption of fluoride ions. This analysis platform was also used for point-of-care quantitative visual detection of fluoride ions in food, water, and toothpaste.

High-fidelity imaging of drug-induced acute gastritis by using a fluorescent and photoacoustic dual-modal probe with good stability in stomach acid.

In consideration of deep tissue imaging and signal fidelity, fluorescent-photoacoustic (PA) dual-modal probes are much more desirable. However, dual-modal imaging of gastritis using molecular probes remains a challenge due to the harsh gastric acid environment in the stomach. Based on the positive correlation between gastritis and cell viscosity, stomach acid-stable and viscosity-activated probes could potentially diagnose gastritis. As a proof of concept, herein, a fluorescent and photoacoustic dual-modal probe (named WSP-1) is revealed for the imaging of drug-induced acute gastritis in vivo. WSP-1 exhibits viscosity-dependent fluorescence emission and photoacoustic signals. A rotatable C-C single bond is incorporated into the D-π-A structure of WSP-1, which could facilitate the formation of the twisted intramolecular charge transfer (TICT) state in a low-viscosity environment (weak fluorescence/PA signal) and the intramolecular charge transfer (ICT) state in a high-viscosity environment (strong fluorescence/PA signal). WSP-1 has demonstrated the capability to target mitochondria and can be utilized to monitor the viscosity enhancement of cells during inflammation. Most importantly, WSP-1 exhibits good optical and structural stability in gastric acid. By leveraging these desirable features of WSP-1, we have achieved fluorescent and 3D photoacoustic in situ imaging of drug-induced acute gastritis following oral administration of WSP-1.

Water bridges as the trigger in an amino functionalized Zn-MOF for highly selective and sensitive fluorescent sensing of water.

Water is a fundamental element for life. The highly selective and sensitive sensing of water is always attractive for mankind in activities such as physiological processes study and extraterrestrial life exploration. Fluorescent MOFs with precise channels and functional groups might specifically recognize water molecules with hydrogen-bond interaction or coordination effects and work as water sensors. As a proof of concept, herein, an amino functionalized Zn-MOF (named as complex 1) with pores that just right for water molecules to form hydrogen bond bridges is revealed for highly selective and sensitive fluorescent sensing of water. The single-crystal X-ray diffraction analysis indicates that the 3D framework of complex 1 is functionalized with free amino groups in the channels. Hydrogen bonds formed in the channel along b-axis as water bridges to connect two adjacent NH2bdc ligands and result in the restriction of intramolecular motions (RIM) which could responsible for the selective turn-on fluorescence response to water. Complex 1 exhibits high sensitive to trace amount of water in organic solvents and could be used for water detection in a wide range water contents. Take advantages of complex 1, portable sensors (complex 1@PMMA) were prepared and used in the highly sensitive water sensing.