Perfluoroalkylation of Triarylamines by EDA Complexes and Ulterior Sensitized [6π]-Electrocyclization to Perfluoroalkylated Endo-Carbazoles. Mechanistic and Photophysical Studies.

Blue LEDs-irradiation of a mixture of N,N,N',N'-tetramethylethylenediamine (TMEDA) and perfluoroalkyl iodides (RF-I) - Electron Donor Acceptor (EDA)-complex - in the presence of triphenylamines (TPAs) in an aqueous solvent mixture afforded mono-perfluoroalkylated triphenylamines (RF-TPA) in good yields. These RF-TPA were further subjected to acetone-sensitized [6π]-electrocyclization at 315 nm-irradiation affording exclusively perfluoroalkylated endo-carbazole derivatives (RF-CBz) in quantitative yields. Mechanistic studies and photophysical properties of products are studied.

Effects of exposure to 3,6-DBCZ on neurotoxicity and AhR pathway during early life stages of zebrafish (Danio rerio).

Polyhalogenated carbazoles (PHCZs) are emerging environmental pollutants, yet limited information is available on their embryotoxicity and neurotoxicity. Therefore, the current work was performed to investigate the adverse effects of 3,6-dibromocarbazole (3,6-DBCZ), a typical PHCZs homolog, on the early life stages of zebrafish larvae. It revealed that the 96-hour post-fertilization (hpf) median lethal concentration (LC50) value of 3,6-DBCZ in zebrafish larvae was determined to be 0.7988 mg/L. Besides, 3,6-DBCZ reduced survival rates at concentrations ≥ 1 mg/L and decreased hatching rates at ≥ 0.25 mg/L at 48 hpf. In behavior tests, it inhibited locomotor activities and reduced the frequency of recorded acceleration states in response to optesthesia (a sudden bright light stimulus) at concentrations ≥ 160 µg/L. Meanwhile, 3,6-DBCZ exposure decreased the frequency of recorded acceleration states in the startle response (tapping mode) at concentrations ≥ 6.4 µg/L. Pathologically, with the transgenic zebrafish model (hb9-eGFP), we observed a strikingly decreased axon length and number in motor neurons after 3,6-DBCZ treatment, which may be ascribed to the activation of the AhR signaling pathway, as evidenced by the molecular docking analysis and Microscale thermophoresis (MST) assay suggested that 3,6-DBCZ binding to AhR-ARNT2 compound proteins. Through interaction with AhR-ARNT, a striking reduction of the anti-oxidative stress (sod1/2, nqo1, nrf2) and neurodevelopment-related genes (elavl3, gfap, mbp, syn2a) were observed after 3,6-DBCZ challenge, accompanied by a marked increased inflammatory genes (TNFß, IL1ß, IL6). Collectively, our findings reveal a previously unrecognized adverse effect of 3,6-DBCZ on zebrafish neurodevelopment and locomotor behaviors, potentially mediated through the activation of the AhR pathway. Furthermore, it provides direct evidence for the toxic concentrations of 3,6-DBCZ and the potential target signaling in zebrafish larvae, which may be beneficial for the risk assessment of the aquatic ecosystems.

Cyclic Azahelicene Dimers Showing Bright Circularly Polarized Luminescence and Selective Fluoride Recognition.

Although helicenes are promising molecules, the synthetic difficulty and tediousness have often been problems, and only small amounts of optically pure helicenes have been obtained by using chiral HPLC in most cases. Herein, aza[7]helicenes or closed-aza[7]helicenes with (1R)-menthyl substituents were selectively synthesized via the intramolecular Scholl reaction, and the diastereomeric pairs were separated by silica gel column chromatography. The optically pure helicenes were further transformed into the corresponding cyclic dimers, and the chiroptical properties were investigated. The rigid π-frameworks of the dimers led to the high molar extinction coefficients and fluorescence quantum yields, while the twisted helicene moieties induced clear Cotton effects and CPL in the visible region, and the high CPL brightness (BCPL) was achieved. Furthermore, the cyclic dimers were found to have the macrocyclic cavity with the two NH groups suitable for the selective binding of a fluoride anion, which induced significantly redshifted fluorescence and CPL in the red region.

An Organophosphorescence Probe with Ultralong Lifetime and Intrinsic Tissue Selectivity for Specific Tumor Imaging and Guided Tumor Surgery.

Organic phosphorescent materials are excellent candidates for use in tumor imaging. However, a systematic comparison of the effects of the intensity, lifetime, and wavelength of phosphorescent emissions on bioimaging performance has not yet been undertaken. In addition, there have been few reports on organic phosphorescent materials that specifically distinguish tumors from normal tissues. This study addresses these gaps and reveals that longer lifetimes effectively increase the signal intensity, whereas longer wavelengths enhance the penetration depth. Conversely, a strong emission intensity with a short lifetime does not necessarily yield robust imaging signals. Building upon these findings, an organo-phosphorescent material with a lifetime of 0.94 s was designed for tumor imaging. Remarkably, the phosphorescent signals of various organic nanoparticles are nearly extinguished in blood-rich organs because of the quenching effect of iron ions. Moreover, for the first time, we demonstrated that iron ions universally quench the phosphorescence of organic room-temperature phosphorescent materials, which is an inherent property of such substances. Leveraging this property, both the normal liver and hepatitis tissues exhibit negligible phosphorescent signals, whereas liver tumors display intense phosphorescence. Therefore, phosphorescent materials, unlike chemiluminescent or fluorescent materials, can exploit this unique inherent property to selectively distinguish liver tumor tissues from normal tissues without additional modifications or treatments.

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts.

N-Acyl carbazoles can be efficiently produced through a single-step process using amides and cyclic diaryliodonium triflates. This convenient reaction is facilitated by copper iodide in p-xylene, using the commonly found activating ligand diglyme. We have tested this method with a wide range of amides and iodonium triflates, proving its versatility with numerous substrates. Beyond carbazoles, we also produced a variety of other N-heterocycles, such as acridines, phenoxazines, or phenazines, showcasing the robustness of our technique. In a broader sense, this new method creates two C-N bonds simultaneously based on a mono-halogenated starting material, thus allowing heterocycle formation with diminished halogen waste.

Full-Color Emissive D-D-A Carbazole Luminophores: Red-to-NIR Mechano-fluorochromism, Aggregation-Induced Near-Infrared Emission, and Application in Photodynamic Therapy.

The preparation of multifunctionalized luminophores with full-color emission based on an identical core skeleton is a significative but challenging research topic. In this work, eight donor-donor-acceptor (D-D-A)-type luminogens based on a central carbazole core bearing a C6 hydrocarbon chain were designed by using different kinds of donor and acceptor units on the left and right, and synthesized in good yields. These D-D-A carbazole derivatives display deep-blue, sky-blue, cyan, green, yellow-green, yellow, orange and red fluorescence in the solid state, achieving full-color emission covering the whole visible light range under UV light illumination. Notably, the dicyano-functionalized triphenylamine-containing carbazole derivative exhibits rare aggregation-induced near-infrared emission and red-to-near-infrared mechano-fluorochromism with high contrast beyond 100 nm. Furthermore, the red-emissive luminogen can serve as a potential candidate for cell imaging and photodynamic therapy (PDT). This work not only provides reference for the construction of full-color emissive systems but also opens a new avenue to the preparation of multifunctionalized luminophores capable of simultaneous application in near-Infrared mechanical-force sensors and PDT fields.

Lycopene abolishes typical polyhalogenated carbazoles (PHCZs)-induced hepatic injury in yellow catfish (Pelteobagrus fulvidraco): Involvement of ROS/PI3K-AKT/NF-κB signaling.

Aquatic ecosystems are being more contaminated with polyhalogenated carbazoles (PHCZs), which raising concerns about their impact on aquatic organisms. Lycopene (LYC) exhibits several beneficial properties for fish via enhance antioxidant defenses and improve immunity. In this study, we attempted to investigate the hepatotoxic effects of typical PHCZs 3, 6-dichlorocarbazole (3,6-DCCZ) and the protective mechanisms of LYC. In this study, we found that yellow catfish (Pelteobagrus fulvidraco) exposure to 3,6-DCCZ (1.2 mg/L) resulted in hepatic inflammatory infiltration and disordered hepatocyte arrangement. Besides, we observed that 3,6-DCCZ exposure resulted in hepatic reactive oxygen species (ROS) overproduction and excessive autophagosome accumulation, accompanied with inhibition of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway. Subsequently, we confirmed that 3,6-DCCZ exposure triggered hepatic uncontrolled inflammatory response via activation of nuclear factor-κB (NF-κB) pathway, along with decreased plasma complement C3 (C3) and complement C4 (C4) levels. Meanwhile, yellow catfish exposed to 3,6-DCCZ exhibit an increased hepatic apoptosis phenomenon, as evidenced by the elevated number of positive TUNEL cells and upregulated expression of caspase3 and cytochrome C (CytC). In contrast, LYC treatment could alleviate the 3,6-DCCZ-induced pathological changes, hepatic ROS accumulation, autophagy, inflammatory response and apoptosis. To sum up, this study provided the demonstration that LYC exerts hepatoprotective effects to alleviate 3,6-DCCZ-induced liver damage by inihibiting ROS/PI3K-AKT/NF-κB signaling in yellow catfish.

Production of Polyhalogenated Carbazoles in Marine Red Alga Corallina officinalis: A Possible Natural Source.

Polyhalogenated carbazoles (PHCZs) have been increasingly detected in the environment as a result of anthropogenic and natural origin. However, it is unclear how PHCZs are naturally produced. In this study, the formation of PHCZs from bromoperoxidase (BPO)-mediated halogenation of carbazole was investigated. A total of six PHCZs were identified in reactions under different incubation conditions. The presence of Br- significantly influenced the formation of PHCZs. The products were first dominated by 3-bromocarbazole and then 3,6-dibromocarbazole as the reactions proceeded. Both bromo- and chlorocarbazoles were identified in the incubations with trace Br-, suggesting the co-occurrence of BPO-catalyzed bromination and chlorination. However, BPO-catalyzed chlorination of carbazole was much weaker than that of bromination. The formation of PHCZs could be attributable to the halogenation of carbazole by reactive halogen species generated from BPO-catalyzed oxidation of Br- and Cl- by H2O2. The halogenation was found to follow a successive substitution order of C-3, C-6, and C-1 on the carbazole ring, forming 3-, 3,6-, and 1,3,6-isomers. Similar to the incubation experiments, six PHCZs were for the first time detected in red algal samples collected from the South China Sea, China, suggesting the biogenesis of PHCZs in marine red algae. Given the widespread distribution of red algae in the marine environment, BPO-catalyzed halogenation of carbazole may be a natural origin for PHCZs.

1,3-Butadiynamides the Ethynylogous Ynamides: Synthesis, Properties and Applications in Heterocyclic Chemistry.

1,3-butadiynamides-the ethynylogous variants of ynamides-receive considerable attention as precursors of complex molecular scaffolds for organic and heterocyclic chemistry. The synthetic potential of these C4-building blocks reveals itself in sophisticated transition-metal catalyzed annulation reactions and in metal-free or silver-mediated HDDA (Hexa-dehydro-Diels-Alder) cycloadditions. 1,3-Butadiynamides also gain significance as optoelectronic materials and in less explored views on their unique helical twisted frontier molecular orbitals (Hel-FMOs). The present account summarizes different methodologies for the synthesis of 1,3-butadiynamides followed by the description of their molecular structure and electronic properties. Finally, the surprisingly rich chemistry of 1,3-butadiynamides as versatile C4-building blocks in heterocyclic chemistry is reviewed by compiling their exciting reactivity, specificity and opportunities for organic synthesis. Besides chemical transformations and use in synthesis, a focus is set on the mechanistic understanding of the chemistry of 1,3-butadiynamides-suggesting that 1,3-butadiynamides are not just simple alkynes. These ethynylogous variants of ynamides have their own molecular character and chemical reactivity and reflect a new class of remarkably useful compounds.

Polyhalogenated carbazoles induce hepatic metabolic disorders in mice via alteration in gut microbiota.

Polyhalogenated carbazoles (PHCZs) have been widely accepted as emerging pollutants, whereas their ecological and health risks remain uncertain. Herein, female and male Sprague-Dawley (SD) mice were treated with four typical PHCZs to investigate their negative consequences, along with alternations in gut microbiota to indicate underlying mechanisms. In female mice, the relative liver weight ratio increased after four PHCZs exposure; 2-bromocarbazole (2-BCZ) increased urine glucose level; 3-bromocarbazole (3-BCZ) decreased the glucose and total cholesterol levels; 3,6-dichlorocarbazole (3,6-DCCZ) decreased glucose level. The only disturbed biochemical index in male mice was the promoted alkaline phosphatase (ALP) level by 3,6-DCCZ. We also found that the differential blood biochemical indices were correlated with gut microbiota. 3-BCZ and 3,6-DCCZ altered Bacteroidetes and Proteobacteria phyla in female and male mice, which were correlated with metabolic disorders. Our findings demonstrated the correlation between PHCZs induced potential hepatotoxicity and metabolic disorders may be due to their dioxin-like potentials and endocrine disrupting activities, and the gender differences might result from their estrogenic activities. Overall, data presented here can help to evaluate the ecological and health risks of PHCZs and reveal the underlying mechanisms.

PM2.5-bound polyhalogenated carbazoles (PHCZs) in urban Beijing, China: Occurrence and the source implication.

Polyhalogenated carbazoles (PHCZs) are recently raising much attention due to their toxicity and ubiquitous environmental distribution. However, little knowledge is known about their ambient occurrences and the potential source. In this study, we developed an analytical method based on GC-MS/MS to simultaneously determine 11 PHCZs in PM2.5 from urban Beijing, China. The optimized method provided low method limit of quantifications (MLOQs, 1.45-7.39 fg/m3) and satisfied recoveries (73.4%-109.5%). This method was applied to analyze the PHCZs in the outdoor PM2.5 (n = 46) and fly ash (n = 6) collected from 3 kinds of surrounding incinerator plants (steel plant, medical waste incinerator and domestic waste incinerator). The levels of ∑11PHCZs in PM2.5 ranged from 0.117 to 5.54 pg/m3 (median 1.18 pg/m3). 3-chloro-9H-carbazole (3-CCZ), 3-bromo-9H-carbazole (3-BCZ), and 3,6-dichloro-9H-carbazole (36-CCZ) were the dominant compounds, accounting for 93%. 3-CCZ and 3-BCZ were significantly higher in winter due to the high PM2.5 concentration, while 36-CCZ was higher in spring, which may be related to the resuspending of surface soil. Furthermore, the levels of ∑11PHCZs in fly ash ranged from 338 to 6101 pg/g. 3-CCZ, 3-BCZ and 36-CCZ accounted for 86.0%. The congener profiles of PHCZs between fly ash and PM2.5 were highly similar, indicating that combustion process could be an important source of ambient PHCZs. To the best of our knowledge, this is the first research providing the occurrences of PHCZs in outdoor PM2.5.

Carbazole-Dendronized Luminescent Radicals.

A series of carbazole-dendronized tris(2,4,6-trichlorophenyl)methyl (TTM) radicals have been synthesized. The photophysical properties of dendronized radicals up to the fourth generation were compared systematically to understand how structure-property relationships evolve with generation. The photoluminescence quantum yield (PLQY) was found to increase with the increasing generation, and the fourth generation (G4TTM) in cyclohexane solution showed a PLQY as high as 63 % at a wavelength of 627 nm (in the deep-red region) from the doublet state. The dendron modification strategy also showed a blue-shift of the emission on increasing the generation number, and the photostability was also increased compared to the bare TTM radical.

Study of the scavenger and vector roles of microplastics for polyhalocarbazoles under simulated gastric fluid conditions.

Microplastics entering the digestive system of living organisms can serve as a carrier of hydrophobic organic pollutants (HOPs), increasing their exposure levels and the health risks they pose to both humans and animals. The desorption kinetics of six polyhalocarbazoles (PHCZs) from 5 mm and 0.15 mm polypropylene (PP) and polyvinyl chloride (PVC) microplastic particles were assessed using a combined microplastics and food system, representing the gastric system of vertebrates and invertebrates. Results showed that the chemical transfer of PHCZs is biphasic and reversible, with rapid exchange occurring within 2-48 h, followed by a period of slow transfer, which continues for weeks to months. The desorption capacity of PHCZs loaded on 0.15 mm microplastic particles was greater than that of 5 mm particles. The bioavailability percentage of PHCZ congeners for PP (24.2%-65.3%) and PVC (43.5%-57.2%) in the vertebrate fluid system were all lower than those in the invertebrate system (34.2%-70.7% for PP and 56.3%-72.7% for PVC, respectively). These findings indicate that physiological conditions, such as polarity, ingestion fluid, and microplastic affect the desorption of PHCZs from microplastics. In addition, desorption from PP was inhibited by the presence of foodstuff loaded with PHCZs due to competition, while desorption from PVC was not significantly affected by the presence of PHCZs contaminant food. Microplastics could provide a cleaning function in gastric fluid systems containing contaminated foodstuff, especially PP, which was capable of competitive adsorption of PHCZs from food. Few investigations have focused on the adverse effects of microplastic ingestion on human health, particularly in their role as vectors for HOPs, compared to other routes of exposure and transport. Therefore, these findings provide valuable insight into the health risks associated with dietary intake of microplastics and HOPs.

Lewis Acid-Catalyzed 2,3-Dihydrofuran Acetal Ring-Opening Benzannulations toward Functionalized 1-Hydroxycarbazoles.

The development of a Lewis acid-catalyzed, intramolecular ring-opening benzannulation of 5-(indolyl)2,3-dihydrofuran acetals is described. The resulting 1-hydroxycarbazole-2-carboxylates are formed in up to 90% yield in 1 h. The dihydrofuran acetals are readily accessed from the reactions of enol ethers and α-diazo-ß-indolyl-ß-ketoesters. To highlight the method's synthetic utility, a formal total synthesis of murrayafoline A, a bioactive carbazole-containing natural product, was undertaken.

Isolation and identification of 1,3,6,8-tetrabromocarbazole - degrading bacteria.

Halogenated carbazoles are a new class of persistent organic pollutants with dioxin-like toxicity, and this study focused on the microbial degradation of 1,3,6,8-tetrabromocarbazole. In this study, a novel 1,3,6,8-tetrabromocarbazole (1,3,6,8-TBCZ) degrading strain TB-1 was isolated from contaminated soil and identified as Achromobacter sp. based on its 16S rRNA gene sequence analysis, morphological, physiological, and biochemical characteristics. The soil sample was collected from a pharmaceutical factory in Suzhou, China. The strain was able to effectively degrade 1 mg L-1 1,3,6,8-TBCZ in 7 d at pH 7.0 and 30 °C with 80% degradation rate. During the process, the intermediate metabolites were identified as Tribromocarbazole, dibromocarbazole and bromocarbazole via gas chromatography mass spectrometry (GC-MS). The results indicated that strain TB-1 may contribute to the bioremediation of polyhalogenated carbazoles (PHCs) in contaminated environment.

Chiral-at-Cage Carboranes for Circularly Polarized Luminescence and Aggregation-Induced Electrochemiluminescence.

Herein, we report the structures of chiral-at-cage carborane derivatives bearing carbazole chromophores that emit circularly polarized luminescence (CPL) and aggregation-induced electrochemiluminescence (AIECL). By adjusting the substituent positions on the carborane derivatives, two chiral luminescent molecules, Cb1 and Cb2, with different properties were obtained. The photoluminescence dissymmetry factors |gPL | of both (R/S)-Cb1 and (R/S)-Cb2 enantiomers in neat films were as high as 6.24×10-3 and 7.38×10-3 , respectively. Cb1 showed a deep blue emission peak at 434 nm in n-pentane. Interestingly, distinct fluorescence and CPL spectra were observed in solvents of different polarities due to the twisted intramolecular charge transfer effect, suggesting its potential use in solvent recognition. Meanwhile, Cb2 exhibited good AIECL property, excellent ECL stability and could be used for determining dopamine concentrations, suggesting its potential applications in biology and diagnosis.

Boosting Room Temperature Phosphorescence Performance by Alkyl Modification for Intravital Orthotopic Lung Tumor Imaging.

Pure organic persistent room temperature phosphorescence (RTP) materials have attracted wide attention owing to their great potential in various applications, particularly in bioimaging. However, it is still a challenge to manufacture organic RTP materials possessing quite high efficiency and long lifetime, owing to the high requirements for triplet excitons. In this study, a series of keto derivatives with efficient RTP in crystals are developed through the regulation of molecular aggregation states by simple alkyl groups, resulting in impressive luminescence performance with a longer lifetime and higher efficiency of up to 868 ms and 51.59%, respectively. All the alkyl-substituted derivatives exhibit bright RTP intensities after heavy grinding with a pestle, indicating their robust RTP features, which are suitable for many fields. Encouraged by the excellent RTP performance of these luminogens in the crystalline state, successful orthotopic lung tumor imaging with a high signal-to-background ratio (SBR) of 65 is demonstrated in this study to provide the promise of pure organic RTP materials for disease diagnosis, which hold the advantages of low autofluorescence interference and high signal-to-background ratio.

Microenvironment-Sensitive Fluorescent Ligand Binds Ascaris Telomere Antiparallel G-Quadruplex DNA with Blue-Shift and Enhanced Emission.

The development of small molecules that can selectively target G-quadruplex (G4) DNAs has drawn considerable attention due to their unique physiological and pathological functions. However, only a few molecules have been found to selectively bind a particular G4 DNA structure. We have developed a fluorescence ligand Q1, a molecular scaffold with a carbazole-pyridine core bridged by a phenylboronic acid side chain, that acts as a selective ascaris telomere antiparallel G4 DNA ASC20 ligand with about 18 nm blue-shifted and enhanced fluorescence intensity. Photophysical properties revealed that Q1 was sensitive to the microenvironment and gave the best selectivity to ASC20 with an equilibrium binding constant Ka =6.04×105  M-1 . Time-resolved fluorescence studies also demonstrated that Q1 showed a longer fluorescence lifetime in the presence of ASC20. The binding characteristics of Q1 with ASC20 were shown in detail in a fluorescent intercalator displacement (FID) assay, a 2-Ap titration experiment and by molecular docking. Ligand Q1 could adopt an appropriate pose at terminal G-quartets of ASC20 through multiple interactions including π-π stacking between aromatic rings; this led to strong fluorescence enhancement. In addition, a co-staining image showed that Q1 is mainly distributed in the cytoplasm. Accordingly, this work provides insights for the development of ligands that selectively targeting a specific G4 DNA structure.

Facile Synthesis of Azahelicenes and Diaza[8]circulenes through the Intramolecular Scholl Reaction.

Carbazole-based aza[7]helicenes and hetero[9]helicenes were successfully obtained via the intramolecular Scholl reaction of 3,6-bis(biphenyl-2-yl)carbazole congeners, while the reaction of 3,6-bis(naphthylphenyl)-appended carbazole gave a triple helicene via an unexpected simultaneous double aryl rearrangement. DFT calculations suggested that the rearrangement proceeded via an arenium cation intermediate. In addition, the reaction of methoxy-appended substrate gave an azahepta[8]circulene via the concurrent C-C bond formation. These helical dyes showed circularly polarized luminescence. The azahepta[8]circulene was further transformed into deeply saddle-distorted dibenzodiaza[8]circulenes as the first example of its solution-based synthesis and unambiguous structural determination.

π-Extended Carbazole Derivatives as Host Materials for Highly Efficient and Long-Life Green Phosphorescent Organic Light-Emitting Diodes.

High-performance organic light-emitting diodes (OLEDs) that use phosphorescent and/or thermally activated delayed fluorescence emitters are capable of realizing 100 % electron-to-photon conversion. The host materials in these OLEDs play crucial roles in determining OLED performance. Carbazole derivatives are frequently used as host materials, among which 3,3-bis(9H-carbazol-9-yl)biphenyl (mCBP) is often used for lifetime testing in scientific studies. In this study, the π conjugation of the carbazole unit was expanded to enhance OLED lifetime by designing and developing two benzothienocarbazole (BTCz)-based host materials, namely m1BTCBP and m4BTCBP. Among these host materials, m1BTCBP formed a highly efficient [Ir(ppy)3 ]-based OLED with an operational luminescence half-life (LT50 ) of over 300 h at an initial luminance of approximately 12000 cd m-2 (current density: 25 mA cm-2 ). The LT50 value at 1000 cd cm-2 was estimated to be about 23 000 h. This performance is clearly higher than that of mCBP-based OLEDs (LT50 ≈8500 h).