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An efficient visible-light photocatalysis-based one-pot amide synthesis method was developed; visible-light irradiation of a mixture of an aldehyde, tert-butyl hydrogen peroxide, and N-chlorosuccinimide using a Ru(bpy)3Cl2 photocatalyst afforded an acid chloride, which subsequently reacted with amine to yield the corresponding amide. The reaction was used to synthesize moclobemide and a D3 receptor intermediate. [ABSTRACT FROM AUTHOR]

Background: Lignocellulosic biomass is an attractive renewable resource for future liquid transport fuel. Efficient and cost-effective production of bioethanol from lignocellulosic biomass depends on the development of a suitable pretreatment system. The aim of this study is to investigate a new pretreatment method that is highly efficient and effective for downstream biocatalytic hydrolysis of various lignocellulosic biomass materials, which can accelerate bioethanol commercialization. Results: The optimal conditions for the hydrogen peroxide-acetic acid (HPAC) pretreatment were 80 °C, 2 h, and an equal volume mixture of H2O2 and CH3COOH. Compared to organo-solvent pretreatment under the same conditions, the HPAC pretreatment was more effective at increasing enzymatic digestibility. After HPAC treatment, the composition of the recovered solid was 74.0 % cellulose, 20.0 % hemicelluloses, and 0.9 % lignin. Notably, 97.2 % of the lignin was removed with HPAC pretreatment. Fermentation of the hydrolyzates by S. cerevisiae resulted in 412 mL ethanol kg-1 of biomass after 24 h, which was equivalent to 85.0 % of the maximum theoretical yield (based on the amount of glucose in the raw material). Conclusion: The newly developed HPAC pretreatment was highly effective for removing lignin from lignocellulosic cell walls, resulting in enhanced enzymatic accessibility of the substrate and more efficient cellulose hydrolysis. This pretreatment produced less amounts of fermentative inhibitory compounds. In addition, HPAC pretreatment enables year-round operations, maximizing utilization of lignocellulosic biomass from various plant sources. [ABSTRACT FROM AUTHOR]

Infection with the human pathogen Vibrio vulnificus leads to the generation of reactive oxygen species (ROS) via NAD(P)H oxidase (Nox) in host cells. In the present study, we employed mutant V. vulnificus strains to identify an essential virulence factor responsible for this ROS generation. We found that repeats-in-toxin A1 (RtxA1) expressed by V. vulnificus acts via Nox1 to induce significant ROS generation in the intestine epithelial cells, which ultimately results in cell death. Furthermore, RtxA1 modulates the small GTPase Rac2, which is known to play an important role in the activation of Nox. When mice were infected by the oral method, in contrast with the wild-type bacteria, an RtxA1-deficient V. vulnificus mutant was unable to induce ROS generation within the intestine and failed to cause death. These findings strongly suggest that RtxA1-induced Rac2 expression is a critical step underlying the pathogenicity of V. vulnificus. [ABSTRACT FROM AUTHOR]

We synthesized a tetrameric amphiphilic molecule ( 1) based on a calix[4]arene building block that self-assembled into different tunable and stable aggregation structures at different pH values in aqueous solution. The amphiphilic calix[4]arene molecule ( 1) formed a spherical structure at pH 3. However, 1formed a hollow necklacelike structure of 500 nm diameter at pH 7. These results indicate that the self-assembled morphologies of 1are strongly dependent on pH values. In addition, a 3D dendritic silver nanostructure was obtained by the self-assembly of 1at pH 7. [ABSTRACT FROM AUTHOR]

(+)-SCH 351448 (Na+ salt A) was synthesized employing ring-closing olefin metathesis reaction of an open diene diester intermediate for construction of the 28-membered macrodiolide structure. The open diene diester was prepared from the monomeric hydroxy carboxylic acid and two different olefin fragments. The monomeric hydroxy acid was synthesized via Julia-Julia coupling reaction of intermediates derived from the same olefinic fragments. Oxane units in these fragments were prepared by radical cyclization reactions of β-alkoxyacrylates. Analogous SCH 351448 salts incorporating other mono- and divalent cations may be prepared. Under acidic conditions, SCH 351448 (Na+ salt A) was the most stable complex, but SCH 351448 (Ca2+ salt) and (Na+ salt B) appear to be physiologically important species. [ABSTRACT FROM AUTHOR]

The trifluoromethyl group can dramatically influence the properties of organic molecules, thereby increasing their applicability as Pharmaceuticals, agrochemicats, or building blocks for organic materials. Despite the importance of this substituent, no general method exists for its installment onto functionalized aromatic substrates. Current methods either require the use of harsh reaction conditions or suffer from a limited substrate scope. Here we report the palladium-catalyzed trifluoromethylation of aryl chlorides under mild conditions, allowing the transformation of a wide range of substrates, including heterocycles, in excellent yields. The process tolerates functional groups such as esters, amides, ethers, acetals, nitrites, and tertiary amines and, therefore, should be applicable to (ate-stage modifications of advanced intermediates. We have also prepared all the putative intermediates in the catalytic cycle and demonstrated their viability in the process. [ABSTRACT FROM AUTHOR]

A terpyridine-based organic−inorganic hybrid molecule was synthesized, and its self-assembled nanostructure with palladium was characterized. The catalyst activity of the nanofibers was examined in the Sonogashira coupling and the Heck reactions at reflux temperature. [ABSTRACT FROM AUTHOR]

Enyne metathesis is unique for its capacity to carry out multiple bond formation in tandem fashion. Its combined use with metallotropic 1,3-shift allowed for the development of a novel strategy for the total synthesis of a conjugated 1,3-diyne-containing natural product (3R,9R,10R)-panaxytriol. [ABSTRACT FROM AUTHOR]

The article describes the highly regioselective Alder ene reaction of 1,3-diynes and 1,3,5-triynes using ruthenium catalysts. The regioselectivity profile was evaluated using symmetrical 1,3-diynes to avoid any potential site-selectivity problem. It indicates that one of the alkynyl moieties of 1,3-diynes not participating in the reaction determines the regiochemistry, while the interplay between steric hindrance and polar substituents at the propargylic sites determines the site-selectivity.

SCH 351448 is a novel activator of low-density lipoprotein receptor promoter, which was discovered from the organic extract of the fermentation broth of a Micromonospora microorganism. The structure of SCH 351448 features a 28-membered macrodiolide consisting of two identical hydroxy carboxylic acid units. Authors report the first total synthesis of this molecule. Synthetic plan called for double combination of units A and B, and the olefin metathesis reaction was envisaged for macrodiolide synthesis.

Provides information about supramolecules. Properties of supramolecules; Significance of fluorescence for chemical trace detection.

Dibenzofurans are naturally occurring molecules that have received considerable attention for a variety of practical applications, such as in pharmaceuticals and electronic materials. Herein, an efficient and eco-friendly method for the synthesis of dibenzofuran derivatives via intramolecular C-O bond formation, which involves the in situ production of a diazonium salt, is described. The transformation requires a diazotizing agent and is promoted by the use of an organic photosensitizer under visible-light irradiation. [ABSTRACT FROM AUTHOR]

Polyphenols have been reported to possess anti-inflammatory activity, thereby act as chemopreventive agents. The objective of this study was to evaluate quercetin and keampferol as anti-inflammatory agents, and to assess their effects on colon cancer cell growth and angiogenic factor production. Human colon cancer cells (HT-29) were treated with 20 and 50 µM of quercetin or kaempferol for 24 to 72 hrs. The level of NO and PGE2 in culture media were measured as inflammatory markers for inflammatory responses. Cell proliferation, MMP activity and VEGF secretion were measured. Results showed that quercetin and kaempferol at 20-50µM reduced NO production, while PGE2 secretion was suppressed only by kaempferol. Both flavonoids inhibited cell proliferation in a dose-dependent manner. No synergistic effect on cell growth in inhibition was observed in 1:1 combination treatment. Kaempferol at 25 µM significantly decreased MMP-2 activity and VEGF production. These results suggest that quercetin and kaempferol possess cancer cell growth inhibitory effects. Keampferol exhibited superior anti-inflammatory activity, thereby significantly reduce angiogenic factor production. [ABSTRACT FROM AUTHOR]

Photoredox catalysis has emerged as a valuable alternative to dark-state catalysis. For the full potential of photoredox catalysis to be utilized, it is imperative to make use of low-energy photons in photoinduced radical processes. We have demonstrated that the use of oxalate as a coreactant provides a useful principle for the photocatalytic production of trifluoromethyl radicals (•CF3) from CF3I upon green or red LED photoirradiation of narrow-bandgap photocatalysts. The photocatalytic cycle involves a radical anion of carbon dioxide (CO2•-) as a reductant for CF3I, which is generated through photoinduced oxidative decarboxylation of oxalate. Electrochemical characterizations and steady-state and transient photophysical investigations were performed to reveal that there are two photoinduced electron-transfer pathways for oxalate-mediated •CF3 generation. [ABSTRACT FROM AUTHOR]

A simple and practical method for the synthesis of substituted oxazoles has been developed using readily available α-bromoketones and benzylamines by visible-light photocatalysis at room temperature. The process, which requires 1 mol % of [Ru(bpy)3]Cl2 photocatalyst with K3PO4 and CCl3Br, is effective for accessing a variety of valuable oxazole compounds. The synthetic utility of our protocol was also demonstrated by preparing a natural product, texaline. [ABSTRACT FROM AUTHOR]

Pyruvate is an endogenous antioxidant and anti-inflammatory substance. The present study was implemented to investigate the protective effect of ethyl pyruvate (EP) against the development and progression of diabetic nephropathy in an in vivo and in vitro model. Diabetic rats were prepared by injecting streptozotocin (65 mg/kg). Those that developed diabetes after 72 h were treated with EP (40 mg/kg) intraperitoneally. Diabetic rats without pyruvate treatment and nondiabetic rats were used for control. As an in vitro experiment, rat mesangial cells cultured primarily from Sprague-Dawley rats were treated in high-glucose (HG, 50 mM) or normal-glucose (NG, 5 mM) conditions and with or without pyruvate. Pyruvate-treated diabetic rats exhibited decreased albuminuria and attenuated NADPH-dependent reactive oxygen species generation. Immunohistochemistry showed reduced laminin, type IV collagen, and fibronectin deposition in the glomeruli compared with nontreated diabetic rats. Parallel changes were shown in tissue mRNA and protein expression levels of monocyte chemoattractant protein-1, transforming growth factor-β1, laminin, fibronectin, and type IV collagen in the kidney. Concordantly, protective effects were also exhibited in the mesangial cell culture system. These findings suggest that pyruvate protects against kidney injury via NADPH oxidase inhibition. The present study established that activation of NADPH oxidase plays a crucial role in diabetes-induced oxidative stress, glomerular hypertrophy, and ECM molecule expression. Pyruvate exhibited a renoprotective effect in the progression of experimental diabetic nephropathy. Future research is warranted to investigate the protective mechanism of pyruvate more specifically in relation to NADPH oxidase in diabetic nephropathy. [ABSTRACT FROM AUTHOR]

A visible-light-induced synthesis of N-H carbazoles from easily accessible 2,2'-diaminobiaryls in the absence of any external photosensitizer is reported. The process only requires t BuONO and natural resources, visible light, and molecular oxygen for the synthesis of N-H carbazoles. Experimental and computational studies support that the in situ formation of a visible-light-absorbing photosensitizing intermediate, benzocinnoline N-imide, is responsible for the activation of triplet molecular oxygen to singlet oxygen that, in turn, promotes the synthesis of carbazole. [ABSTRACT FROM AUTHOR]

Halogenated organic compounds are important anthropogenic chemicals widely used in chemical industry, biology, and pharmacology; however, the persistence and inertness of organic halides cause human health problems and considerable environmental pollution. Thus, the elimination or replacement of halogen atoms with organic halides has been considered a central task in synthetic chemistry. In dehalogenation reactions, the consecutive single-electron transfer from reducing agents generates the radical and corresponding carbanion and thus removes the halogen atom as the leaving group. Herein, we report a new strategy for an efficient chemoselective hydrodehalogenation through the formation of stable carbanion intermediates, which are simply achieved by using highly mobile two-dimensional electrons of inorganic electride [Ca2N]+ ⋅ e- with effective electron transfer ability. The consecutive single-electron transfer from inorganic electride [Ca2N]+ ⋅ e- stabilized free carbanions, which is a key step in achieving the selective reaction. Furthermore, a determinant more important than leaving group ability is the stability control of free carbanions according to the s character determined by the backbone structure. We anticipate that this approach may provide new insight into selective chemical formation, including hydrodehalogenation. [ABSTRACT FROM AUTHOR]

Conspectus: Owing to their unique biological, physical, and chemical properties, fluoroalkylated organic substances have attracted significant attention from researchers in a variety of disciplines. Fluoroalkylated compounds are considered particularly important in pharmaceutical chemistry because of their superior lipophilicity, binding selectivity, metabolic stability, and bioavailability to those of their nonfluoroalkylated analogues. We have developed various methods for the synthesis of fluoroalkylated substances that rely on the use of visible-light photoredox catalysis, a powerful preparative tool owing to its environmental benignity and mechanistic versatility in promoting a large number of synthetically important reactions with high levels of selectivity. In this Account, we describe the results of our efforts, which have led to the development of visible-light photocatalytic methods for the introduction of a variety of fluoroalkyl groups (such as, −CF3, −CF2R, −CH2CF3, −C3F7, and −C4F9) and arylthiofluoroalkyl groups (such as, −CF2SPh, −C2F4SAr, and −C4F8SAr) to organic substances. In these studies, electron-deficient carbon-centered fluoroalkyl radicals were successfully generated by the appropriate choice of fluoroalkyl source, photocatalyst, additives, and solvent. The redox potentials of the photocatalysts and the fluoroalkyl sources and the choice of sacrificial electron donor or acceptor as the additive affected the photocatalytic pathway, determining whether an oxidative or reductive quenching pathway was operative for the generation of key fluoroalkyl radicals. Notably, we have observed that additives significantly affect the efficiencies and selectivities of these reactions and can even change the outcome of the reaction by playing additional roles during its course. For instance, a tertiary amine as an additive in the reaction medium can act not only as a sacrificial electron donor in photoredox catalysis but also as a hydrogen atom source, an elimination base for dehydrohalogenation of the intermediate, and also a Brønsted base for deprotonation. In the same context, the selection of solvent is also critical since it affects the rate and selectivity of reactions depending upon its polarity and reagent solubilizing ability and plays additional roles in the process, for example, as a hydrogen atom source. By clearly understanding the roles of additives and solvent, we designed several controlled fluoroalkylation reactions where different products were formed selectively from the same starting substrates. In addition, we could exploit one of the most important advantages of radical reactions, that is, the use of unactivated π-systems such as alkenes, alkynes, arenes, and heteroarenes as radical acceptors without prefunctionalization. Furthermore, fluoroalkylation processes under mild room-temperature reaction conditions tolerate various functional groups and are therefore easily applicable to late-stage modifications of highly functionalized advanced intermediates. [ABSTRACT FROM AUTHOR]

Visible-light-induced arylthiofluoroalkylations of unactivated heteroaromatics and alkenes have been developed utilizing readily available arylthiofluoroalkyl sources. This method enables simultaneous installation of sulfur and fluoroalkyl moieties, two important functional groups, which demonstrates its potential use for late-stage modifications in the synthesis of functional molecules. This method can be easily utilized to fine-tune the properties of lead molecules in drug development by controlling the number of fluorine atoms in the reagents. [ABSTRACT FROM AUTHOR]

HL156A is a novel AMP-activated protein kinase (AMPK) activator. We aimed to investigate the protective mechanism of HL156A against peritoneal fibrosis (PF) in in vivo and in vitro models. The rat PF model was induced by daily intraperitoneally injection of chlorhexidine (CHX) solution containing 0.1% CHX gluconate and 15% ethanol for 4 wk. The rats in the treatment group were treated with HL156A (1 mg·kg-1·day-1). Control rats were injected with vehicle alone. In vitro, cultured rat peritoneal mesothelial cells (RPMCs) were treated with either high glucose (HG; 50 mM), normal glucose (NG; 5 mM), NG+HL156A, or HG+HL156A. HL156A in supplemented rats ameliorated peritoneal calcification, cocoon formation, bowel obstruction, and PF. Immunohistochemistry showed reduced fibronectin accumulation in the peritoneum of HL156A-treated rats compared with those injected with CHX alone. HL156A treatment of RPMCs inhibited HG-induced myofibroblast transdifferentiation and markers of epithelial-mesenchymal transition (EMT). Moreover, HL156A ameliorated HG-induced transforming growth factor-β1, Smad3, Snail, and fibronectin expression in the RPMCs via AMPK upregulation. These results suggest that HL156A exhibits a protective effect in PF progression. Further research is warranted to seek the therapeutic potential of HL156A as an antifibrotic agent in peritoneal dialysis patients. [ABSTRACT FROM AUTHOR]

Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the first step of polyamine biosynthesis that is associated with cell growth and tumor formation. Existing catalytic inhibitors of ODC have lacked efficacy in clinical testing or displayed unacceptable toxicity. In this study, we report the identification of an effective and nontoxic allosteric inhibitor of ODC. Using computer docking simulation and an in vitro ODC enzyme assay, we identified herbacetin, a natural compound found in flax and other plants, as a novel ODC inhibitor. Mechanistic investigations defined aspartate 44 in ODC as critical for binding. Herbacetin exhibited potent anticancer activity in colon cancer cell lines expressing high levels of ODC. Intraperitoneal or oral administration of herbacetin effectively suppressed HCT116 xenograft tumor growth and also reduced the number and size of polyps in a mouse model of APC-driven colon cancer (ApcMin/+). Unlike the well-established ODC inhibitor DFMO, herbacetin treatment was not associated with hearing loss. Taken together, our findings defined the natural product herbacetin as an allosteric inhibitor of ODC with chemopreventive and antitumor activity in preclinical models of colon cancer, prompting its further investigation in clinical trials. [ABSTRACT FROM AUTHOR]

A visible light-induced process for selective difluoroalkylation of unactivated alkenes has been developed. The choice of base is crucial for governing the chemoselectivity of the process to produce difluoroalkylated alkanes and alkenes. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aim: Vascular stiffness is associated with cardiovascular mortality in dialysis patients and related with vascular calcification and microvascular inflammation. The objective of this study is to compare predictability of two different vascular calcification scoring systems using plain radiographs in peritoneal dialysis (PD) patients. Methods: Vascular stiffness was represented by heart-to-femoral pulse wave velocity (hfPWV) in our 79 PD patients. Peripheral vascular calcification score (PVCS) and abdominal aortic calcification score (AACS) were measured from plain radiographs. Microvascular inflammation was represented by peritoneal protein clearance (PPC). Regression analysis and the receiver operating characteristic (ROC) curve analysis were used for analysis. Results: The hfPWV revealed correlation with PVCS and AACS independently. In the ROC curve analysis, area under the curve (AUC) of PVC score was 0.7119 ( P = 0.006), and AUC of AACS were 0.6960 ( P = 0.011). After multiple linear regression analysis, PVCS remained as a predictor of vascular stiffness (R2 = 0.579, β = 0.210, P = 0.038). The combination of PVCS and PPC exhibited a trend toward better predictability for vascular stiffness (AUC 0.7738, P = 0.001) than any of the two parameters alone. Conclusion: It is assumed that the PVCS system is more predictable for vascular stiffness in our study. Moreover, the combination of PVCS and PPC might be more useful as a screening test for vascular stiffness. [ABSTRACT FROM AUTHOR]

RSK2 is a widely expressed serine/threonine kinase, and its activation enhances cell proliferation. Here, we report that ATF1 is a novel substrate of RSK2 and that RSK2-ATF1 signaling plays an important role in EGF-induced neoplastic cell transformation. RSK2 phosphorylated ATF1 at Ser-63 and enhanced ATF1 transcriptional activity. Docking experiments using the crystal structure of the RSK2 N-terminal kinase domain combined with in vitro pulldown assays demonstrated that eriodictyol, a flavanone found in fruits, bound with the N-terminal kinase domain of RSK2 to inhibit RSK2 N-terminal kinase activity. In cells, eriodictyol inhibited phosphorylation of ATF1 but had no effect on the phosphorylation of RSK, MEK1/2, ERK1/2, p38 or JNKs, indicating that eriodictyol specifically suppresses RSK2 signaling. Furthermore, eriodictyol inhibited RSK2-mediated ATF1 transactivation and tumor promoter-induced transformation of JB6 Cl41 cells. Eriodictyol or knockdown of RSK2 or ATF1 also suppressed Ras-mediated focus formation. Overall, these results indicate that RSK2-ATF1 signaling plays an important role in neoplastic cell transformation and that eriodictyol is a novel natural compound for suppressing RSK2 kinase activity. [ABSTRACT FROM AUTHOR]

Abstract: Thermal, structural and optical properties of Nd3+ ions in tellurite glass (TeO2–ZnO–Na2O–Li2O–Nb2O5) have been investigated. Differential thermal analysis revealed reasonably good forming tendency of the glass composition. FTIR spectra were used to analyze the functional groups present in the glass. Judd–Ofelt intensity parameters were derived from the absorption spectrum and used to calculate the radiative lifetime, branching ratio and stimulated emission cross-section of the 4F3/2→4I9/2, 11/2, 13/2 transitions. The quantum efficiency of the 4F3/2 level is comparable as well as higher than the typical value of the other tellurite based glasses. The decay from the 4F3/2 level is found to be single exponential for different concentrations of Nd3+ ions with a shortening of lifetime with increasing concentration. The experimental values of branching ratio and saturation intensity of 4F3/2→4I11/2 transition indicate the favourable lasing action with low threshold power. [Copyright &y& Elsevier]

Anthraquinone-based fluorescent receptor 1 was immobilized on mesoporous silica (AFMS) or on silica particles (AFSP) via a sol–gel reaction. The sensing abilities of AFMS and AFSP were studied by addition of the anions F−, Cl−, Br−, I− and HSO4− to water suspensions of the assayed solid. The addition of fluoride ions to a suspension of AFMS resulted in a large decrease in the fluorescence intensity of the anthraquinone of AFMS. Thus, fluoride ions bind to two urea N–H protons of receptor 1 in AFMS. In contrast, the addition of Cl−, Br−, I− or HSO4− did not reduce the fluorescence of AFMS. In the case of AFSP, the sensitivity for fluoride ions was 10 times lower than that of AFMS due to the immobilization of smaller amounts of receptor 1 on the silica particles. A linear response of AFMS upon the addition of fluoride ions was observed between 0.50 μM and 10.0 μM, with a detection limit of ∼0.50 μM. These results suggest that mesoporous silica with its large surface area is useful as a supporting material. Furthermore, receptor 1 was also immobilized on a glass slide surface by a sol–gel reaction. The fluorescence of 1 immobilized on a glass slide was quenched when dipped into F− solution. On the other hand, no fluorescence change was observed in Cl− solution. These results imply that 1 immobilized on a glass slide is applicable as a portable fluorescent sensor for detection of fluoride ions in the biological and environmental fields. [ABSTRACT FROM AUTHOR]

A method for trifluoromethylation of alkenes has been developed employing visible light photoredox catalysis withCF3I, Ru(Phen)3Cl2, and DBU. This process works especially well for terminal alkenes to give alkenyl-CF3 products with only E-stereochemistry. The mild reaction conditions enable the trifluoromethylation of a range of alkenes that bear various functional groups. [ABSTRACT FROM AUTHOR]