Leveraging Pt/Ce1-xLaxO2-δ To Elucidate Interfacial Oxygen Vacancy Active Sites for Aerobic Oxidation of 5-Hydroxymethylfurfural.

The interfacial oxygen-defective sites of oxide-supported metal catalysts are generally regarded as active centers in diverse redox reactions. Identification of their structure-property relationship at the atomic scale is of great importance but challenging. Herein, a series of La3+-doped three-dimensionally ordered macroporous CeO2 (3D-Ce1-xLaxO2-δ) were synthesized and applied as supports for Pt nanoparticles. The pieces of evidence from a suite of in-situ/ex-situ characterizations and theoretical calculations revealed that the La3+-mono-substituted La-□(-Ce)2 sites (where □ represents an oxygen vacancy) exhibited superior charge transfer ability, behaving as trapping centers for Pt nanoparticles. The resulting interfacial Ptδ+/La-□(-Ce)2 sites served as the reversible active species in the aerobic oxidation of 5-hydroxymethylfurfural to boost catalytic performance by simultaneously promoting oxygen activated capacity and the cleavage of O-H/C-H bonds of adsorbed hydroxymethyl groups. Consequently, the Pt/3D-Ce0.9La0.1O2-δ catalyst possessing the highest number of Ptδ+/La-□(-Ce)2 sites showed the best catalytic performance with 99.6% yield to 2,5-furandicarboxylic acid in 10 h. These results offer more insights into the promoting mechanism of interfacial oxygen-defective sites for the liquid-phase aerobic oxidation of aldehydes and alcohols.

Advances in Chiral Metal-Organic and Covalent Organic Frameworks for Asymmetric Catalysis.

Asymmetric catalysis is of crucial importance owing to the huge and rising demand for optically pure substances. Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), as two emerging crystalline porous materials, have presented great promising applications for heterogeneous asymmetric catalysis. The unique properties, such as, highly regular porous structures, prominent structural tunability, and well-ordered catalytic sites, render chiral MOFs (CMOFs) and chiral COFs (CCOFs) highly active and enantioselective for a large number of asymmetric catalytic organic transformations. Furthermore, they provide a useful platform for facile mechanistic understanding and catalyst design. This review provides an overview of the advancements in CMOFs and CCOFs for asymmetric catalysis. The designs, syntheses and structures of these crystalline porous materials, and their asymmetric catalytic performance are described. And the perspectives on challenges and opportunities in development of CMOFs and CCOFs are discussed. It is anticipated that this review will shed light on the heterogeneous asymmetric catalysis with CMOFs and CCOFs and motivate further research in this promising field.

Asymmetric Oxygen Vacancies: the Intrinsic Redox Active Sites in Metal Oxide Catalysts.

To identify the intrinsic active sites in oxides or oxide supported catalysts is a research frontier in the fields of heterogeneous catalysis and material science. In particular, the role of oxygen vacancies on the redox properties of oxide catalysts is still not fully understood. Herein, some relevant research dealing with M1-O-M2 or M1-□-M2 linkages as active sites in mixed oxides, in oxide supported single-atom catalysts, and at metal/oxide interfaces of oxide supported nanometal catalysts for various reaction systems is reviewed. It is found that the catalytic activity of these oxides not only depends on the amounts of oxygen vacancies and metastable cations but also shows a significant influence from the local environment of the active sites, in particular, the symmetry of the oxygen vacancies. Based on the recent progress in the relevant fields, an "asymmetric oxygen vacancy site" is introduced, which indicates an oxygen vacancy with an asymmetric coordination of cations, making oxygen "easy come, easy go," i.e., more reactive in redox reactions. The establishment of this new mechanism would shed light on the future investigation of the intrinsic active sites in oxide and oxide supported catalysts.

Band-Gap and Charge Transfer Engineering in Red Phosphorus-Based Composites for Enhanced Visible-Light-Driven H2 Evolution.

It is known that the low lifetime of photogenerated carriers is the main drawback of elemental photocatalysts. Therefore, a facile and versatile one-step strategy to simultaneously achieve the oxygen covalent functionalization of amorphous red phosphorus (RP) and in situ modification of CdCO3 is reported. This strategy endows RP with enhanced charge carrier separation ability and photocatalytic activity by coupling band-gap engineering and heterojunction construction. The as-prepared nCdCO3 /SO-RP (n=0.1, 0.25, 0.5, 1.0) composites exhibited excellent photocatalytic H2 evolution activity (up to 516.3 µmol g-1 h) from visible-light-driven water splitting (λ>400 nm), which is about 17.6 times higher than that of pristine RP. By experimental and theoretical investigations, the roles of surface oxygen covalent functionalization, that is, prolonging the lifetime of photogenerated carriers and inducing the negative shift of the conduction band potential, were studied in detail. Moreover, the charge transfer mechanism of these composites has also been proposed. In addition, these composites are stable and can be reused at least for three times without significant activity loss. This work may provide a good example of how to promote the activity of elemental photocatalysts by decorating their atomic structure.

Germacrane Sesquiterpenoids as a New Type of Anticardiac Fibrosis Agent Targeting Transforming Growth Factor ß Type I Receptor.

A germacrane sesquiterpenoid library containing 30 compounds (2-31) was constructed by structural modification of a major component aristolactone (1) from the traditional Chinese medicine Aristolochia yunnanensis. Compound 11 was identified as a promising anticardiac fibrosis agent by systematic screening of this library. 11 could inhibit the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagens in transforming growth factor ß 1 (TGFß1)-stimulated cardiac fibroblasts at a micromolar level and ameliorate myocardial fibrosis and heart function in abdominal aortic constriction (AAC) rats at 5 mg/kg dose. Mechanistic study revealed that 11 inhibited the TGFß/small mother against decapentaplegic (Smad) signaling pathway by targeting TGFß type I receptor (IC50 = 14.9 ± 1.6 nM). The structure-activity relationships (SARs) study indicated that the unsaturated γ-lactone ring and oxidation of C-1 were important to the activity. These findings may provide a new type of structural motif for future anticardiac fibrosis drug development.

(+)-Isobicyclogermacrenal and spathulenol from Aristolochia yunnanensis alleviate cardiac fibrosis by inhibiting transforming growth factor ß/small mother against decapentaplegic signaling pathway.

Cardiac fibrosis contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. Antifibrotic therapies are likely to be a crucial strategy in curbing many fibrosis-related cardiac diseases. In our previous study, an ethyl acetate extract of a traditional Chinese medicine Aristolochia yunnanensis Franch. was found to have a therapeutic effect on myocardial fibrosis in vitro and in vivo. However, the exact chemicals and their mechanisms responsible for the activity of the crude extract have not been illustrated yet. In the current study, 10 sesquiterpenoids (1-10) were isolated from the active extract, and their antifibrotic effects were systematically evaluated in transforming growth factor ß 1 (TGFß1)-stimulated cardiac fibroblasts and NIH3T3 fibrosis models. (+)-Isobicyclogermacrenal (1) and spathulenol (2) were identified as the main active components, being more potent than the well-known natural antifibrotic agent oxymatrine. Compounds 1 and 2 could inhibit the TGFß1-induced cardiac fibroblasts proliferation and suppress the expression of the fibrosis biomarkers fibronectin and α-smooth muscle actin via down-regulation of their mRNA levels. The mechanism study revealed that 1 and 2 could inhibit the phosphorylation of TGFß type I receptor, leading to the decrease of the phosphorylation levels of downstream Smad2/3, then consequently blocking the nuclear translocation of Smad2/3 in the TGFß/Smad signaling pathway. These findings suggest that 1 and 2 may serve as promising natural leads for the development of anticardiac fibrosis drugs.

Evodialones A and B: Polyprenylated Acylcyclopentanone Racemates with a 3-Ethyl-1,1-diisopentyl-4-methylcyclopentane Skeleton from Evodia lepta.

Two polyprenylated acylcyclopentanone racemates, evodialones A (1) and B (2), featuring a 3-ethyl-1,1-diisopentyl-4-methylcyclopentane skeleton, were isolated from an extract of the aerial parts of Evodia lepta. Evodialone A (1) was resolved by chiral-phase HPLC to afford a pair of enantiomers, (+)- and (-)-evodialones A (1b/1a), while evodialone B (2) could not be resolved. Their structures were elucidated by spectroscopic analysis and a combination of computational techniques including gauge-independent atomic orbital calculation of 1D NMR data and experimental and TDDFT-calculated ECD spectra. A putative biosynthetic pathway of 1 and 2 starting from the monocyclic polyprenylated acylphloroglucinols is proposed. All the isolates were screened for the antimicrobial activity in vitro, and 1a and 1b showed moderate inhibitory activities against several pathogenic fungi with MICs values of 17.1-68.3 µM.

Prenylated flavonoids as potent phosphodiesterase-4 inhibitors from Morus alba: Isolation, modification, and structure-activity relationship study.

The bioassay-guided phytochemical study of a traditional Chinese medicine Morus alba led to the isolation of 18 prenylated flavonoids (1-18), of which (±)-cyclomorusin (1/2), a pair of enantiomers, and 14-methoxy-dihydromorusin (3) are the new ones. Subsequent structural modification of the selected components by methylation, esterification, hydrogenation, and oxidative cyclization led to 14 more derivatives (19-32). The small library was screened for its inhibition against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among them, nine compounds (1-5, 8, 10, 16, and 17) exhibited remarkable activities with IC50 values ranging from 0.0054 to 0.40 µM, being more active than the positive control rolipram (IC50 = 0.62 µM). (+)-Cyclomorusin (1), the most active natural PDE4 inhibitor reported so far, also showed a high selectivity across other PDE members with the selective fold greater than 55. The SAR study revealed that the presence of prenyls at C-3 and/or C-8, 2H-pyran ring D, and the phenolic hydroxyl groups were important to the activity, which was further supported by the recognition mechanism study of the inhibitors with PDE4 by using molecular modeling.

Biscembranoids and Cembranoids from the Soft Coral Sarcophyton elegans.

Two novel biscembranoids, sarelengans A and B (1 and 2), five new cembranoids, sarelengans C-G (3-7), along with two known cembranoids (8 and 9) were isolated from the South China Sea soft coral Sarcophyton elegans. Their structures were determined by spectroscopic and chemical methods, and those of 1, 4, 5, and 6 were confirmed by single crystal X-ray diffraction. Compounds 1 and 2 represent the first example of biscembranoids featuring a trans-fused A/B-ring conjunction between the two cembranoid units. Their unique structures may shed light on an unusual biosynthetic pathway involving a cembranoid-∆8 rather than the normal cembranoid-∆¹ unit in the endo-Diels-Alder cycloaddition. Compounds 2 and 3 exhibited potential inhibitory effects on nitric oxide production in RAW 264.7 macrophages, with IC50 values being at 18.2 and 32.5 µM, respectively.

Synthesis of the novel PARP-1 inhibitor AG-690/11026014 and its protective effects on angiotensin II-induced mouse cardiac remodeling.

We previously identified AG-690/11026014 (6014) as a novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor that effectively prevented angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. In the present study, we reported a new synthesis route for 6014, and investigated its protective effects on Ang II-induced cardiac remodeling and cardiac dysfunction and the underlying mechanisms in mice. We designed a new synthesis route to obtain a sufficient quantity of 6014 for this in vivo study. C57BL/6J mice were infused with Ang II and treated with 6014 (10, 30, 90 mg·kg-1·d-1, ig) for 4 weeks. Then two-dimensional echocardiography was performed to assess the cardiac function and structure. Histological changes of the hearts were examined with HE staining and Masson's trichrome staining. The protein expression was evaluated by Western blot, immunohistochemistry and immunofluorescence assays. The activities of sirtuin-1 (SIRT-1) and the content of NAD+ were detected with the corresponding test kits. Treatment with 6014 dose-dependently improved cardiac function, including LVEF, CO and SV and reversed the changes of cardiac structure in Ang II-infused mice: it significantly ameliorated Ang II-induced cardiac hypertrophy evidenced by attenuating the enlargement of cardiomyocytes, decreased HW/BW and LVW/BW, and decreased expression of hypertrophic markers ANF, BNP and ß-MHC; it also prevented Ang II-induced cardiac fibrosis, as implied by the decrease in excess accumulation of extracellular matrix (ECM) components collagen I, collagen III and FN. Further studies revealed that treatment with 6014 did not affect the expression levels of PARP-1, but dose-dependently inhibited the activity of PARP-1 and subsequently restored the activity of SIRT-1 in heart tissues due to the decreased consumption of NAD+ and attenuated Poly-ADP-ribosylation (PARylation) of SIRT-1. In conclusion, the novel PARP-1 inhibitor 6014 effectively protects mice against AngII-induced cardiac remodeling and improves cardiac function. Thus, 6014 might be a potential therapeutic agent for heart diseases..

New lanostane-type triterpenoids from the fruiting body of Ganoderma hainanense.

Five new lanostane-type triterpenoids, ganoderenses A-E (1-5), two new lanostane nor-triterpenoids, ganoderenses F and G (6 and 7), along with 13 known analogues (8-20) were isolated from the fruiting body of Ganoderma hainanense. Their structures were determined by combined chemical and spectral methods, and the absolute configurations of compounds 1 and 13 were confirmed by single crystal X-ray diffraction. All compounds were evaluated for inhibitory activity against thioredoxin reductase (TrxR), a potential target for cancer chemotherapy with redox balance and antioxidant functions, but were inactive.

Degradation of polycyclic aromatic hydrocarbons in crumb tyre rubber catalysed by rutile TiO2 under UV irradiation.

The polycyclic aromatic hydrocarbons (PAHs) in crumb tyre rubber were firstly degraded under UV irradiation in the presence of rutile TiO2 and hydrogen peroxide. The effects of light intensity, catalyst amount, oxidant amount, initial pH value, co-solvent content, and reaction time on degradation efficiency of typical PAHs in crumb tyre rubber were studied. The results indicated that UV irradiation, rutile TiO2, and hydrogen peroxide were beneficial to the degradation of PAHs and co-solvent could accelerate the desorption of PAHs from crumb tyre rubber. Up to 90% degradation efficiency of total 16 PAHs could be obtained in the presence of rutile TiO2 (1 wt%) and hydrogen peroxide (1.0 mL) under 1800 µW cm(-2) UV irradiation for 48 h. The high molecular weight PAHs (such as benz(a)pyrene) were more difficult to be degraded than low molecular weight PAHs (such as phenanthrene, chrysene). Moreover, through the characterization of reaction solution and degradation products via GC-MS, it was proved that the PAHs in crumb tyre rubber were successfully degraded.