Construction of a tetrabenzotetrathia[8]circulene by a "fold-in" oxidative fusion reaction: synthesis and optical properties.

Herein we report the first synthesis of a tetrabenzotetrathia[8]circulene by a "fold-in" type oxidative fusion reaction. Compared to the pristine tetrathia[8]circulene, the four-fold benzoannulation slightly weakened the antiaromatic character of the central COT ring. The tetrabenzotetrathia[8]circulene exhibited fluorescence at room temperature, and phosphorescence at 77 K with a phosphorescence quantum yield of 11.7%.

Hydrophilic Cocrystals with Water Switched Luminescence.

Utilizing water molecules to regulate the luminescence properties of solid materials is highly challenging. Herein, we develop a strategy to produce water-triggered luminescence-switching cocrystals by coassembling hydrophilic donors with electron-deficient acceptors, where 1,2,4,5-Tetracyanobenzene (TCNB) was used as the electron acceptor and pyridyl benzimidazole derivatives were used as the electron donors enabling multiple hydrogen-bonds. Two cocrystals, namely 2PYTC and 4PYTC were obtained and showed heat-activated emission, and such emission could be quenched or weakened by adding water molecules. The cocrystal structure exhibited the donor molecule that can form multiple hydro bonds with water and acceptor molecules due to the many nitrogen atoms of them. The analyses of the photophysical data, powder X-ray diffraction, and other data confirmed the reversible fluorescence "on-off" effects were caused by eliminating and adding water molecules in the crystal lattice. The density functional theory calculations indicate that the vibration of the O-H bond of water molecules in the cocrystal can absorb the excitation energy and suppress fluorescence. Furthermore, the obtained cocrystals also showed temperature, humidity, and H+ /NH4 + responsive emission behavior, which allows their applications as thermal and humidity sensors, and multiple information encryptions. This research paves the way for preparing intelligent hydrophilic organic cocrystal luminescent materials.

High-Performance Nonfused Electron Acceptor with Precisely Controlled Side Chain Fluorination.

Modification of the molecular packing of nonfullerene acceptors through fluorination represents one of the most promising strategies to achieve highly efficient organic solar cells (OSCs). In this work, three nonfused electron acceptors, namely, DTCBT-Fx (x = 0, 5, 9) with precisely controlled amounts of fluorine atoms in the side chains are designed and synthesized, and the effect of side chain fluorination is systematically studied. The results demonstrate that the light absorption, energy levels, molecular ordering, and film morphology could be effectively tuned by precisely controlling the side chain fluorination. DTCBT-F5 with an appropriate fluorine functionalization exhibits suitable miscibility with the donor polymer (PM6), leading to diminished charge recombination and improved charge carrier mobility. Consequently, a promising power conversion efficiency of 12.7% was obtained for DTCBT-F5-based solar cells, which outperforms those OSCs based on DTCBT-F0 (11.4%) and DTCBT-F9 (11.6%), respectively. This work demonstrates that precise control of the fluorine functionalization in side chains of nonfused electron acceptors is an effective strategy for realizing highly efficient OSCs.

Planar and Helical Dinaphthophenazines.

In this study, we report the synthesis of a series of planar and helical dinaphthophenazines by cyclocondensation reactions between the newly developed 9,10-bis((triisopropylsilyl)ethynyl)anthracene-1,2-dione and different diamines. Their optoelectronic and electrochemical properties are studied by ultraviolet-visible (UV-vis) spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and density functional theory calculations.

Triphenyleno[1,2-c:7,8-c']bis([1,2,5]thiadiazole) as a V-Shaped Electron-Deficient Unit to Construct Wide-Bandgap Amorphous Polymers for Efficient Organic Solar Cells.

The backbone shape of semiconducting polymers strongly affects their electronic properties and morphologies in films, yet the conventional design principle for building blocks focuses on using linear main chains to maintain high crystallinity. Here, we developed a V-shaped unit, triphenyleno[1,2-c:7,8-c']bis([1,2,5]thiadiazole) (TPTz), featuring two 1,2,5-thiadiazole rings fused to a triphenylene core with strong electron-withdrawing properties and an extended conjugation plane. We used TPTz to prepare a highly soluble copolymer, PTPTz-indacenodithiophene (IDT), which exhibited a wide bandgap of 1.94 eV and energy levels suitable for the donor polymer in organic solar cells (OSCs) in combination with non-fullerene acceptors. Despite the amorphous nature of the polymer film, single-junction OSCs with PTPTz-IDT:Y6 as the active layer achieved a power conversion efficiency of 10.4% (JSC = 19.8 mA cm-2; VOC = 0.80 V; fill factor = 0.66), which is the highest value reported for a single-junction OSC with IDT-based donor polymers. This work demonstrates that TPTz is a promising electron-acceptor unit for developing functional polymers with zigzag structures.

Meta-Analysis of Renal Replacement Therapy for Burn Patients: Incidence Rate, Mortality, and Renal Outcome.

Background: Renal replacement therapy (RRT) was often needed by some severe burn patients with acute kidney injury (AKI). The primary aim of this study was to review incidence rate and mortality of RRT in severe burn patients. Second aims were to review RRT complications and renal outcome. Methods: We searched multiple databases for studies published between 1 January 1960 and 31 December 2019. Studies about adult populations with burn injury, providing epidemiologic data on prevalence or mortality of RRT, were included. Results: A total of selected 57 studies, including 27,437 patients were enrolled in our analysis. The prevalence rates of RRT were 8.34% (95% CI 7.18-9.5%) in all burn patients and 37.05% (95% CI 29.85-44.24%) in AKI patients. The mortality of all burn patients with RRT was 65.52% (95% CI 58.41-72.64%). The prevalence rates of RRT in sample size≥100 group were 6.86% (95% CI 5.70-8.03%), which was lower than that of <100 group (17.61%, 95% CI 13.39-21.82%). With the increase of TBSA, the prevalence of RRT may have the increasing trend. The prevalence rates of RRT in Asian group was 12.75% (95% CI 9.50-16.00%), which was higher than that of European (10.45%, 95% CI 7.30-13.61%) and North America group (5.61%, 95% CI 4.27-6.95%). The prevalence rates of RRT in 2010-2019 group was 12.22% (95% CI 10.09-14.35%), which was higher than that of 2009-2000 group (5.17%, 95% CI 2.88-7.46%). The prevalence rates of RRT in 1989 and before group was the lowest, which was 1.56% (95% CI 0-3.68%). However, there was no significant correlation between the year of publication and the mortality of burn patients with RRT. Dialysis-requiring AKI in burn patients could increases the risk of chronic kidney disease progression and end-stage renal disease. About 35% of RRT patients need to maintain haemodialysis temporarily, even if they survive and leave hospital. Conclusions: The prevalence rate of RRT is about 6-8%; approximately, one-third of burn patients with AKI need RRT. The prevalence rate of RRT increased over time, but the mortality did not change. The prevalence rates of RRT in Asian group was higher than that of European and North America group.

Improved Synthesis of ortho-Phenylene-bridged Cyclic Tetrapyrroles and Oxidative Fusion Reactions Toward Substituted Tetraaza[8]circulenes.

Hetero[8]circulenes have emerged as novel functionalized heteronanographenes that show various promising functions such as bright fluorescence, charge transporting, and redox reactivities. One of the effective synthetic strategy is the fold-in type oxidative fusion reaction of ortho-phenylene-bridged cyclic tetrapyrroles, whose construction, however, is not well-sophisticated in terms of reproducibility and possibility for versatile derivatization. In this paper, a "reverse" coupling strategy has been developed, which enabled synthesis of opp-type low symmetric analogues of cyclic tetrapyrroles. Oxidative fusion reaction conditions to afford tetraaza[8]circulenes have also been reinvestigated and improved. Substituent effects of cyclic tetrapyrroles and tetrabenzotetraaza[8]circulenes are studied for solid-state structures and packing structures, redox potentials, and optical properties.

A Sterically Congested Nitrogenated Benzodipentaphene with a Double π-Expanded Helicene Structure.

Herein, we describe a series of three sterically congested nitrogenated benzodipentaphenes, one of which shows a highly distorted aromatic backbone with an unprecedented double π-expanded helicene structure.

Facile synthesis of fluorescent hetero[8]circulene analogues with tunable solubilities and optical properties.

Hetero[8]circulenes are an interesting class of polycyclic heteroaromatic molecules having rigid and planar structures, which are promising in light of their potential applications for OLEDs, OFETs and so forth. Although their synthetic methods have been developed in some specific cases, a facile synthetic protocol of novel hetero[8]circulenes with tunable properties is highly desirable. We herein report the unexpected formation of methoxy-substituted quasi-aza[8]circulene and its conversion into unprecedented triazaoxa[8]circulene. The structures and optical properties were comparatively studied. Remarkably, triazaoxa[8]circulene is highly soluble in THF, acetone and DMSO mainly because of effective hydrogen-bonding of the NH moieties to these solvents. Their highly soluble nature in various solvents enabled us to study the solvent effects of these molecules. In particular, triazaoxa[8]circulene displays a high fluorescence quantum yield of 0.72 in DMSO. Furthermore, enantiomeric separation of highly distorted quasi-aza[8]circulene was successfully achieved by chiral HPLC. Thus, these novel hetero[8]circulene derivatives are practically useful fluorescent nanographene-like molecules with intriguing optical properties.

Synthesis, Structures, and Optical Properties of Azahelicene Derivatives and Unexpected Formation of Azahepta[8]circulenes.

Polycyclic heteroaromatic compounds including pyrrole units are promising functional scaffolds owing to their electron-rich nature, bright fluorescence, and applicability to anion recognition at the pyrrolic hydrogen atom. We report herein the effective synthesis of pseudo-aza[5]helicene and aza[7]helicene derivatives, and unexpected formation of azahepta[8]circulenes by oxidative fusion reactions. By choosing reaction conditions and peripheral substituents attached at the terminal indole moieties, we obtained aza[7]helicenes 10 a-c and azahepta[8]circulenes 11 a,c selectively in moderate to good yields. Their solid-state structures have been revealed by X-ray diffraction analysis. UV/Vis absorption, emission, and cyclic voltammetry of these compounds were studied in comparison with those of previously reported tetraaza[8]circulene (TA8C), a symmetric and planar molecule. Furthermore, the enantiomeric separation of dimethyl-substituted aza[7]helicene 10 b was achieved, and the racemization kinetics have been elucidated both theoretically and experimentally. This work illustrates a wealth of advantages of pyrrole incorporation into the polycyclic aromatic scaffolds in terms of synthetic aspects, structural variation, and optical tuning.

Closed Pentaaza[9]helicene and Hexathia[9]/[5]helicene: Oxidative Fusion Reactions of ortho-Phenylene-Bridged Cyclic Hexapyrroles and Hexathiophenes.

Oxidative fusion reactions of ortho-phenylene-bridged cyclic hexapyrroles and hexathiophenes furnished novel closed helicenes in a selective manner. X-Ray diffraction analysis unambiguously revealed the structures to be a closed pentaaza[9]helicene, the longest azahelicene reported so far, and an unexpected double-helical structure of hexathia[9]/[5]helicene, whose formation was assumed to result from multiple oxidative fusion along with a 1,2-aryl shift. The pentaaza[9]helicene exhibited well-defined emission with high fluorescence quantum yield (ΦF =0.31) among the known [9]helicenes. Chiral resolution of the racemic pentaaza[9]helicene and hexathia[9]/[5]helicene were achieved by chiral-phase HPLC and the enantiomers were characterized by circular dichroism spectra and DFT calculations.

Exploring the "fold-in" strategy toward the construction of a highly-strained triazasumanene skeleton.

The synthesis of tribenzotriazasumanene was attempted on the basis of the "fold-in" synthesis of cyclic pyrrole trimer 5 and its analogues under oxidative and reductive conditions. While unexpectedly triply-fused product 6 was obtained in the oxidation of 5 with FeCl3 and AgOTf, the reductive coupling of hexabromo-tri-N-methylpyrrole trimer 9 furnished partially fused product 10. These results indicate the potential of the "fold-in" strategy that gave complementary outcomes depending on the reaction conditions.

Sequential N-Alkylations of Tetrabenzotetraaza[8]circulene as a Tool To Tune Its Optical Properties.

Sequential N-alkylations of tetrabenzotetraaza[8]circulene provided mono-, di-, tri, and tetra-N-alkylated products in a controlled manner. Curiously, only opp isomer was obtained as a di-N-alkylated product. Upon increase of the N-alkyl groups, the absorption and emission spectra exhibit continuous red-shifts, and the excited-state lifetimes become shortened, probably because of increased steric congestion at the nitrogen atoms that causes the central core to deviate from planarity. Mixed N-substituted [8]circulenes have been also prepared.

ortho-Phenylene-Bridged Cyclic Oligopyrroles: Conformational Flexibilities and Optical Properties.

ortho-Phenylene-bridged cyclic trimeric oligopyrrole C3 and hexameric oligopyrrole C6 were synthesized by Suzuki-Miyaura coupling reactions. The twisted structures of C3 and C6 were unambiguously revealed by X-ray diffraction analysis. The optical properties of these cyclic oligopyrroles were compared with linear oligopyrrole L3 and cyclic tetramer C4. The cyclic oligopyrroles exhibited large Stokes shifts and blue fluorescence with high quantum yields in solution and in the solid state. In addition, selective N-methylation and N-tolylation of C3 were used to tune the optical and electrochemical properties by changing the molecular twists and conformational flexibilities. Throughout these studies, the structure-property relationship of these cyclic strained oligopyrroles has been illustrated as an interesting molecular motif for novel cyclic π-conjugated systems.

ABT-737, a Bcl-2 Selective Inhibitor, and Chloroquine Synergistically Kill Renal Cancer Cells.

Renal cell carcinoma (RCC) is the most common malignancy in the kidney in the world, and the 5-year overall survival for patients remains poor due to the lack of effective treatment strategies. Although ABT-737, as a Bcl-2/Bcl-xL inhibitor, has recently emerged as a novel cancer therapeutic reagent, apoptosis induced by ABT-737 is often blocked in several types of cancer cells. This study investigated whether the combination of the small-molecule BH3 mimetic ABT-737 and the lysosome inhibitor chloroquine was an effective strategy for treating renal cancer cells. We found that the combination of ABT-737 and chloroquine synergistically decreased cell viability when compared to treatment with either single reagent. Cell apoptosis induced by a combined treatment was markedly inhibited by the caspase inhibitors z-DEVD-FMK and z-VAD-FMK. It was also inhibited by cathepsin inhibitor E-64 and CTSI (cathepsin inhibitor), which suggested that apoptosis was dependent on the cascade of caspase activation and cathepsins released from lysosomes. Furthermore, we found that ABT-737 could increase the cell level of ROS, which triggers cathepsin-mediated cell death and augments the role of chloroquine in cell death. So the combination of ABT-737 and chloroquine was an effective strategy for the treatment of renal cancer cells, and this combined strategy may widen the therapeutic window of ABT-737 and chloroquine as well as enhance the clinical efficacy of synergistic drug combinations.

Synthesis of a Tetrabenzotetraaza[8]circulene by a "Fold-In" Oxidative Fusion Reaction.

Tetrabenzotetraaza[8]circulene (1) has been synthesized in good yield by a "fold-in" oxidative fusion reaction of a 1,2-phenylene-bridged cyclic tetrapyrrole. X-ray diffraction analysis of 1 has revealed a planar square structure with a central cyclooctatetraene (COT) core that shows little alternation of the bond lengths. Despite these structural features, 1 shows aromatic-like character, such as sharp absorption bands, high fluorescence quantum yields (Φ(F)=0.55 in THF), and a single exponential fluorescence decay with τ(F)=3.8 ns. These observations indicate a dominant contribution of an [8]radialene-like π conjugation and hence aromatic character of the local aromatic segments in 1.

Flotillin-1 expression in human clear-cell renal cell carcinoma is associated with cancer progression and poor patient survival.

The present study was designed to elucidate the expression levels and the proliferative effect of flotillin-1, an integral membrane protein encoded by the FLOT1 gene, in human clear-cell renal cell carcinoma (RCC). Flotillin has been implicated in other types of cancer, but the role of flotillin in RCC has not been established. Immunohistochemistry and western blotting were used to determine FLOT1 protein expression levels in RCC samples from 182 patients who underwent nephrectomy. FLOT1 mRNA expression levels were analyzed using reverse-transcription (RT) and RT-quantitative polymerase chain reaction (PCR). The association between FLOT1 expression levels in the tumor samples and patient survival time was examined using Kaplan­Meier analysis. To demonstrate the proliferative effect of FLOT1 on RCC cells, a FLOT1 vector was transfected into four RCC cell lines and FLOT1 expression was inhibited using small interfering RNA. The proliferative ability of the RCC cells was investigated using a WST-1 assay and xenograft experiments with BALB/C nude mice. The results demonstrated that FLOT1 expression levels were significantly higher in RCC cell samples from patients than in healthy renal tissue, and the expression levels were associated with tumor stage, size and histological grade. In addition, FLOT1 significantly enhanced the proliferation of RCC cell lines in vitro and in vivo. These findings suggest that FLOT1, which is upregulated in RCC, is involved in RCC cell proliferation, tumorigenesis and progression. Therefore, FLOT1 is an independent prognostic marker and therapeutic target for patients with clear-cell RCC.

Concentrated sodium chloride catheter lock solution--a new effective alternative method for hemodialysis patients with high bleeding risk.

BACKGROUND: Locking catheter with heparin may increase bleeding risk of some hemodialysis (HD) patients. Hence, the security and effectivity of 10% concentrated sodium chloride (CSC) used as an alternative method for patients with high bleeding risk need to be investigated. METHODS: Seventy-two patients inserted temporary central venous catheters were divided into two groups randomly. A total of 3125 U/mL heparin saline (HS) was used in HS group and 10% CSC in CSC group to lock catheters. Heparin-free HD was used for the first time and plasma specimens were collected to test coagulation indicators before catheter-locking (at the end of HD) and at 30 min after it. Then, blood flow velocities (BFVs), incidences of catheter thrombosis, etc. were followed up at each time of HD. RESULTS: Activated partial thromboplastin time (APTT) of two groups had no difference at the end of heparin-free HD (27.100 [25.675-28.950] vs. 27.250 [25.150-29.575] second, p = 0.933), but at 30 minutes after using different catheter lock solutions, APTT of HS group was obviously longer than CSC group (50.100 [41.275-65.400] vs. 27.500 [25.525-29.875] second, p < 0.001). Catheters' retaining time of two groups were the same (p = 0.306), so did the average BFVs (p > 0.05). But catheters' thrombosis incidence and urokinase usage of HS group were less than CSC group (p < 0.05). CONCLUSION: Comparing with HS group, thrombosis incidences of CSC group increased, but catheters' retaining time and average BFVs remained the same and coagulation indicators of it were unaffected. Therefore, it can be an effective alternative lock method for HD patients with high bleeding risk.

Glycated albumin may be a choice, but not an alternative marker of glycated hemoglobin for glycemic control assessment in diabetic patients undergoing maintenance hemodialysis.

BACKGROUND: It has been suggested that glycated hemoglobin (HbA1c) underestimate the actual glycemic control levels in maintenance hemodialysis (MHD) patients, because of anemia and the using of erythropoietin (EPO); it was recommended that glycated albumin (GA) should be an alternative marker. Therefore, the assessment performances of glycemic control were compared between GA and HbA1c in this research by referring to mean plasma glucose (MPG) in diabetes mellitus (DM) patients undergoing MHD or not. METHODS: MPG was calculated according to the data registered at enrollment and follow-up 2 months later and corresponding HbA1c, albumin (ALB), GA, etc. were measured in 280 cases. A case-control study for comparing GA and HbA1c was done among the groups of MHD patients with DM (n=88) and without DM (NDM; n=90), and non-MHD ones with DM (n=102) using MPG for an actual glycemic control standard. RESULTS: In these 3 groups, only for DM patients' (whether undergoing MHD or not), GA and HbA1c correlated with MPG significantly (P < 0.01). Through linear regression analysis, it could be found that the regression curves of GA almost coincided in MHD and non-MHD patients with DM, because the intercepts (2.418 vs. 2.329) and slopes (0.053 vs. 0.057) were very close to each other. On the contrary, regression curves of HbA1c did not coincide in the two groups, because variance of the slopes (0.036 vs. 0.052) were relatively large. Through comparing receiver operating characteristic (ROC) areas under the curve (AUC), it could be understood that the assessment performances of GA and HbA1c in MHD patients were lower than those in non-MHD ones, and assessment performance of HbA1c in MHD patients was better than GA (P < 0.05). In addition, the effects of Hb and EPO dose on HbA1c, or that of ALB on GA were unobvious in our study. CONCLUSIONS: Actual glycemic control level in MHD patients with DM may be underestimated by HbA1c, and it could be avoided by GA; however, glycemic evaluating performance of HbA1c may be still better than that of GA. Therefore, HbA1c should not be replaced completely although GA can be used as a choice to monitor glycemic level.

Colorless to purple-red switching electrochromic anthraquinone imides with broad visible/near-IR absorptions in the radical anion state: simulation-aided molecular design.

The large redshift of near-infrared (NIR) absorptions of nitro-substituted anthraquinone imide (Nitro-AQI) radical anions, relative to other AQI derivatives, is rationalized based on quantum chemical calculations. Calculations reveal that the delocalization effects of electronegative substitution in the radical anion states is dramatically enhanced, thus leading to a significant decrease in the HOMO-LUMO band gap in the radical anion states. Based on this understanding, an AQI derivative with an even stronger electron-withdrawing dicyanovinyl (di-CN) substituent was designed and prepared. The resulting molecule, di-CN-AQI, displays no absorption in the Vis/NIR region in the neutral state, but absorbs intensively in the range of λ=700-1000 (λmax ≈860 nm) and λ=1100-1800 nm (λmax ≈1400 nm) upon one-electron reduction; this is accompanied by a transition from a highly transmissive colorless solution to one that is purple-red. The relationship between calculated radical anionic HOMO-LUMO gaps and the electron-withdrawing capacity of the substituents is also determined by employing Hammett parameter, which could serve as a theoretical tool for further molecular design.