Low‐Temperature Polymerization of Olefins in the Presence of Titanium Monoamidinate/MAO Catalyst

This paper reports the predominantly syndiotactic‐specific polymerization of propylene in the presence of titanium monoamidinate/methylaluminoxane (MAO) catalysts. The same catalysts, depending on the reaction conditions, also promote either predominantly 1,4‐cis or 1,4‐trans polymerization of 1,3‐butadiene and polymerization of styrene either to highly syndiotactic or to stereoirregular polymer. Some preliminary information about the features of propylene polyinsertion is also reported.

Expansion of the 20–24 ppm region of the ¹³C NMR spectrum of sample 2. The starred resonance at 21.75 ppm and the shoulders are not assigned.     

Isolation,purification, and biological activity of mono- and dihydroxylated paclitaxel metabolites from human feces

Three metabolites of the cytotoxic drug paclitaxel (Taxol) were isolated and purified from the feces of cancer patients receiving the agent as an intravenous infusion. The procedures involved sample homogenization in water followed by liquid-liquid extraction with diethyl ether and high-performance liquid chromatography (HPLC). Approximately 1–3.5 mg of each metabolite was obtained from 100 g of feces. As judged from the chromatographic traces of analytical HPLC with ultraviolet (UV) detection at 227 nm, the purity of each compound was >97%. On-line photodiode-array detection demonstrated that the UV spectrum of the isolated compounds closely resembles that of the parent drug. Mass spectrometry provided evidence that these metabolites are mono- and dihydroxy-substituted derivatives, namely, 6-hydroxypaclitaxel, 3-p-hydroxypaclitaxel, and 6,3-p-dihydroxypaclitaxel. The two 6-hydroxy-substituted metabolites were shown to have lost their cytotoxicity in in vitro clonogenic assays using the A2780 human ovarian carcinoma and the CC531 rat colon-carcinoma tumor cell lines. In addition, the metabolites showed reduced myelotoxic effects as compared with paclitaxel in an in vitro hemopoietic progenitor toxicity assay. Our procedure for the isolation and purification of paclitaxel metabolites in milligram quantities should be useful for testing the biological activities of these compounds and for the preparation of calibration standards essential for pharmockinetics studies.     

Synthesis of a Multiblock Copolymer of cis‐1,4‐Polybutadiene and Poly(3‐buten‐1‐ol)

Synthesis of a multiblock copolymer composed of cis‐1,4‐polybutadiene (PBd) segments and poly(3‐buten‐1‐ol) segments is performed via successive hydroboration and oxidation of cis‐1,4/syn‐1,2‐multiblock PBd. The ratio of functionalization can be controlled by changing the amount of the borane reagent. The obtained polymer shows two distinctive glass‐transition temperatures, which correspond to the cis‐1,4‐PBd block and the poly(3‐buten‐1‐ol) block. These thermal properties clearly show that the functionalization of the PBd proceeds keeping the elastic property derived from cis‐1,4 segment.

     

动态下HTDB/TDI体系凝胶化的研究

利用哈克流变仪制备了热塑性聚丁二烯型聚氨酯。获得了反应挤出的工艺条件。研究表明，当不加催化剂时，由于反应温度比较高而使产物出现热交联，此交 物不溶于沸腾的甲苯和二甲苯；当加入催化剂后，反应温度可大幅度下降，热交联消失。产物可不地沸腾的二甲苯。但在甲苯中仍然存在物理性的凝胶，所以在甲苯中的凝胶含量不能作为反应的程度的判据。虽然硬段的含量不到１０％，但凝胶含量可达到９０％。利用甲苯抽提，研究了凝胶含量     

Direct inhibition of ERK1/2 phosphorylation as a possible mechanism for the antiproliferative action of 3,4-diOH-PCB3 in the MCF-7 cell line

Our previously published data showed that 260 h of exposure to 3,4-diOH-PCB3 decreased proliferation in the MCF-7 cell line. In the present study, we sought to determine whether this is due to action on the SHBG/cAMP/PKA system, activation of which can inhibit cell proliferation, or to direct inhibition of ERK1/2 phosphorylation. MCF-7 human breast cancer cells were treated for 72 h with 4-monochlorobiphenyl (PCB3), 4′-hydroxy-4-monochlorobiphenyl (4-OH-PCB3) or 3′4′-dihydroxy-4-monochlorobiphenyl (3,4-diOH-PCB3) (300 nM). After the completion of the treatment, cell proliferation was measured with a BrdU incorporation assay. SHBG, cAMP, PKA and ERK1/2 levels in the cells were determined via ELISA.PCB3 and 4-OH-PCB3 had no effect on extra- or intracellular SHBG levels, while a stimulation of SHBG intra- but not extracellular levels was noted in cells exposed to 3,4-diOH-PCB3. Both, pre- and co-incubation with SHBG decreased the proliferation of 3,4-diOH-PCB3-treated cells. Neither PCB3 nor its metabolite had an effect on the cAMP/PKA pathway. A decrease of both ERK1/2 forms was noted under the influence of 3,4-diOH-PCB3. In conclusion, the data presented clearly showed that the antiproliferative action of 3,4-diOH-PCB3 is not mediated by activation of the SHBG/AMP/PKA pathway, but many other plasma membrane receptors seem to be involved in the non-genomic action of 3,4-diOH-PCB3, and instead is due to direct inhibition of the ERK1/2 system.     

Hydroxylated polychlorinated biphenyls increase reactive oxygen species formation and induce cell death in cultured cerebellar granule cells

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that bioaccumulate in the body, however, they can be metabolized to more water-soluble products. Although they are more readily excreted than the parent compounds, some of the metabolites are still hydrophobic and may be more available to target tissues, such as the brain. They can also cross the placenta and reach a developing foetus. Much less is known about the toxicity of PCB metabolites than about the parent compounds. In the present study, we have investigated the effects of eight hydroxylated (OH) PCB congeners (2′-OH PCB 3, 4-OH PCB 14, 4-OH PCB 34, 4′-OH PCB 35, 4-OH PCB 36, 4′-OH PCB 36, 4-OH PCB 39, and 4′-OH PCB 68) on reactive oxygen species (ROS) formation and cell viability in rat cerebellar granule cells. We found that, similar to their parent compounds, OH-PCBs are potent ROS inducers with potency 4-OH PCB 14 < 4-OH PCB 36 < 4-OH PCB 34 < 4′-OH PCB 36 < 4′-OH PCB 68 < 4-OH PCB 39 < 4′-OH PCB 35. 4-OH PCB 36 was the most potent cell death inducer, and caused apoptotic or necrotic morphology depending on concentration. Inhibition of ERK1/2 kinase with U0126 reduced both cell death and ROS formation, suggesting that ERK1/2 activation is involved in OH-PCB toxicity. The results indicate that the hydroxylation of PCBs may not constitute a detoxification reaction. Since OH-PCBs like their parent compounds are retained in the body and may be more widely distributed to sensitive tissues, it is important that not only the levels of the parent compounds but also the levels of their metabolites are taken into account during risk assessment of PCBs and related compounds.     

Identification of cytochrome P450 isoforms involved in the metabolism of Syl930, a selective S1PR1 agonist acting as a potential therapeutic agent for autoimmune encephalitis

Syl930 is a novel sphingosine-1-phosphate receptor subtype 1 (S1PR₁) agonist for the treatment of autoimmune encephalitis with promising receptor selectivity and little risk of bradycardia. Syl930 could be reversibly converted to its phosphorylated metabolite, acting as the active form to provide therapeutic effects, but eliminated principally in the form of oxidative metabolites. The aim of the present study was to identify the cytochrome P450 isoforms (CYPs) responsible for the oxidative metabolism of Syl930. Considerable production of hydroxylated metabolite (Syl930-M1) was found in both rat blood and tissue homogenates in vivo and in vitro. Moreover, another hydroxylated metabolite, Syl930-M2, was detected in human, beagle dog and cynomolgus monkey liver microsomes with significant differences in the K_m, V_max and CL_int of the metabolites among species. CYP1A1, CYP2J2, CYP4F2 and CYP3A4 were identified to be the major CYPs mediated in the hydroxylation of Syl930 by using 14 recombinant human CYPs, selective chemical inhibitors and monoclonal antibodies against CYPs. The multiple CYPs mediated oxidation was believed to be one of the reasons for the relatively short elimination half-life of Syl930.     

Thermal Conductivity of Polybutadiene Rubber from Molecular Dynamics Simulations and Measurements by the Heat Flow Meter Method

Thermal conductivities of polybutadiene rubbers crosslinked by 2.4 and 2.8 phr of sulfur have been found to be functions of temperature via molecular dynamics (MD) simulations using the Green–Kubo method. From an analysis of the heat flux autocorrelation functions, it has been revealed that the dominant means of heat transport in rubbers is governed by deformations of polymeric chains. Thermal conductivities of rubber samples vulcanized by 2.4 and 2.8 phr of sulfur have been measured by the heat flow meter method between 0 ∘C and 60 ∘C at atmospheric pressure. The temperature dependencies of the thermal conductivities of rubbers and their glass transition temperatures derived from MD simulations are in good agreement with the literature and experimental data. Details are discussed in the paper.