Direct copolymerization of ethylene with protic comonomers enabled by multinuclear Ni catalysts.

Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.

Nickel-Catalyzed Propylene/Polar Monomer Copolymerization.

Nickel complexes bearing bidentate alkylphophine-phenolate ligands were synthesized and applied to the polymerization of propylene and the copolymerization of propylene and polar monomers. Therein, the use of bulky alkyl substituents on the phosphorus atom was crucial for the formation of highly regioregular polypropylenes. Theoretical calculations suggested that the 1,2-insertion of propylene is favored over the 2,1-insertion in these nickel-catalyzed (co)polymerization reactions. The substituent at the ortho position relative to the oxido group greatly influences the polymerization activity, the molecular weight, and stereoregularity of the polypropylenes. This method delivers moderately isotactic ([mm] ≤ 68%) crystalline polypropylenes. The present system represents the first example for a nickel-catalyzed regiocontrolled copolymerization of propylene and polar monomers such as but-3-en-1-ol, but-3-en-1-yl acetate, and tert-butyl allylcarbamate.

Overexpression of stathmin/oncoprotein 18 correlates with poorer prognosis and interacts with p53 in oral squamous cell carcinoma.

PURPOSE: The stathmin/oncoprotein 18 (STMN1) is overexpressed in various human cancers. The aim of our study was to investigate its clinical significance and interaction with p53 in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Stathmin expression was assessed by Oncomine, Gene Expression Omnibus (GEO) database, western blotting, and reverse transcription polymerase chain reaction. We investigated the relationship between stathmin expression and clinical characteristics among 109 OSCC patients by immunohistochemical staining. The prognosis factors were analyzed using univariate and multivariate analysis. Immunoprecipitation assay and The Cancer Genome Atlas (TCGA) analysis were used to detect the relationship between mutant p53 and stathmin. RESULTS: Stathmin was overexpressed in OSCC. In immunohistochemical analysis, high stathmin expression correlated with gender (P = 0.040), T stage (P = 0.015), TNM stage (P = 0.045), and pathological differentiation (P = 0.000). We found a correlation between the stathmin expression and overall survival (P = 0.027). Multivariate analysis suggested only lymph node metastasis (P = 0.007) and stathmin expression (P = 0.013) as independent prognostic factors. There was interaction between stathmin and p53 in OSCC cell lines with mutant p53 through immunoprecipitation assay. CONCLUSION: These results suggest that overexpression of stathmin could contribute to cancer progression/prognosis, and that interaction between p53 and stathmin may contribute to the gain-of-function of p53.

Charge Variants of an Avastin Biosimilar Isolation, Characterization, In Vitro Properties and Pharmacokinetics in Rat.

The similarity between a proposed biosimilar product and the reference product can be affected by many factors. This study is designed to examine whether any subtle difference in the distribution of the charge variants of an Avastin biosimilar can affect its in vitro potency and in vivo PK. Here, the acidic, basic and main peak fractions of a biosimilar product were isolated using high-performance cation-exchange chromatography and were subjected to various studies to compare their in vitro properties and in vivo PK profile. A serial of analytical methods, including size exclusion chromatography (SEC), imaged capillary isoelectric focusing (icIEF) capillary zone electrophoresis (CZE) and cation-exchange chromatography (CEX-HPLC) were also used to characterize the isolated charge variants. The kinetics constant was measured using a Biacore X100 system. The study indicates the biosimilar product has a high similarity with avastin in physicochemical properties. The potency in vitro and PK profile in rat of charge variants and biosimilar product are consistent with avastin.

Copolymerization of Ethylene and Polar Monomers by Using Ni/IzQO Catalysts.

The replacement of precious metals in catalysis by earth-abundant metals is currently one of the urgent challenges for chemists. Whereas palladium-catalyzed copolymerization of ethylene and polar monomers is a valuable method for the straightforward synthesis of functionalized polyolefins, the corresponding nickel-based catalysts have suffered from poor thermal tolerance and low molecular weight of the polymers formed. Herein, we report a series of neutral nickel complexes bearing imidazo[1,5-a]quinolin-9-olate-1-ylidene (IzQO) ligands. The Ni/IzQO system can catalyze ethylene polymerization at 50-100 °C with reasonable activity in the absence of any cocatalyst, whereas most known nickel-based catalysts are deactivated at this temperature range. The Ni/IzQO catalyst was successfully applied to the copolymerization of ethylene with allyl monomers to obtain the corresponding copolymers with the highest molecular weight reported for a Ni-catalyzed system.

[Expression and localization of FGFR family in squamous cell carcinoma of head and neck].

PURPOSE: To investigate the expression and localization of FGFR family in squamous cell carcinoma of head and neck (SCCHN) cell lines. METHODS: Total protein was extracted from 10 SCCHN cell lines and the expression of FGFR was detected by Western blot. The localization of FGFR was further demonstrated by immunofluorescence staining in SCC25 and HN4 cell lines. Gray value was measured by Image J. GraphPad Prism 5.01 software package was used for data processing and analysis. RESULTS: FGFR1 expression was detected in 6/10 cell lines and FGFR2, 3, 4 was detectable in all cell lines. The expression of FGFR1, 2, 4 was mainly in the nucleus and cytoplasm while FGFR3 was predominantly localized in cytoplasm. CONCLUSIONS: FGFR shows co-expression in SCCHN cell lines, which may be associated with the tumorigenesis and development of SCCHN.

A highly efficient and enantioselective intramolecular Cannizzaro reaction under TOX/Cu(II) catalysis.

An asymmetric intramolecular Cannizzaro reaction of aryl and alkyl glyoxals with alcohols has been realized with an unprecedented high level of enantioselectivity, on the basis of a newly developed congested TOX ligand and a gradual liberation protocol of active glyoxals from glyoxal monohydrates. Preliminary results suggested a mechanism of enantioselective addition of alcohols to glyoxals contributing most to the stereoselectivity, other than by the dynamic kinetic resolution of hemiacetal intermediates.

Water as an activator for palladium(II)-catalyzed olefin polymerization.

By a reasonable combination of the Wacker reaction and olefin polymerization processes, water proves to be an excellent activator for the palladium(II)-catalyzed polymerization of ethylene and it provides a safe, environmental-friendly and handy initiator for olefin polymerization. The activity of the olefin polymerization is comparable to reactions catalyzed by the corresponding alkylated cationic palladium complexes.