A Study of Diphenylfumaronitrile and Furan‐Substituted Diketopyrrolopyrrole Alternating Copolymer and Its Thin‐Film Transistors

A fused aromatic furan‐substituted diketopyrrolopyrrole and novel diphenylfumaronitrile conjugated building blocks are used for the synthesis of an alternating copolymer ( DPFN‐DPPF ) via Suzuki polycondensation. In this paper, the first attempt to use the diphenylfumaro­nitrile building block for the synthesis of conjugated polymer is described. The number‐average and weight‐average ­molecular weights calculated for DPFN‐DPPF are 20 661 and 66 346 g mol^?1, respectively. The optical bandgap calculated for DPFN‐DPPF is 1.53 eV whereas the highest occupied molecular orbital (HOMO) value calculated by photoelectron spectroscopy in air (PESA) is 5.50 eV. The calculated HOMO value is lower, which is suitable for stable organic electronic devices. DPFN‐DPPF polymer is used as an active layer in bottom‐contact bottom‐gate organic thin‐film transistor devices and the thin film exhibits a hole mobility of 0.20 cm² V^?1 s^?1 in air.

     

The calcium channel ligand FPL 64176 enhances L-type but inhibits N-type neuronal calcium currents

One strategy for isolating neuronal L-type calcium (Ca(2+)) currents, which typically comprise a minority of the whole cell current in neurons, has been to use pharmacological agents that increase channel activity. This study examines the effects of the benzoyl pyrrole FPL 64176 (FPL) on L-type Ca(2+) currents and compares them to those of the dihydropyridine (+)-202-791. At micromolar concentrations, both agonists increased whole cell current amplitude in PC12 cells. However, FPL also significantly slowed the rate of activation and elicited a longer-lasting slow component of the tail current compared to (+)-202-791. In single channel cell-attached patch recordings, FPL increased open probability, first latency, mean closed time and mean open time more than (+)-202-791, with no difference in unitary conductance. These gating differences suggest that, compared to (+)-202-791, FPL decreases transition rates between open and closed conformations. Where examined, the actions of FPL and (+)-202-791 on whole cell L-type currents in sympathetic neurons appeared similar to those in PC12 cells. In contrast to its effects on L-type current, 10 microM FPL inhibited the majority of the whole cell current in HEK cells expressing a recombinant N-type Ca(2+) channel, raising caution concerning the use of FPL as a selective L-type Ca(2+) channel agonist in neurons.     

吡咯野百合碱对培养的牛肺动脉内皮细胞NO、细胞内钙及胶原凝胶收缩的影响

目的通过吡咯野百合碱(monocrotaline pyrrole,MCTP)对牛肺动脉内皮细胞(calf pulmonary artery endothelial cells,CPAE)NO、细胞内钙和胶原凝胶收缩的影响,探讨MCTP导致肺动脉高压的机理.方法采用fura-2测定细胞NO及细胞内钙的含量;采用胶原凝胶收缩实验分析CPAE的功能.结果MCTP减少ACh所致NO及细胞内钙增加的作用,分别从(6.1±1.3)%减少到(1.5±1.1)%和从(70.2±3.2)nmol·L-1减少到(26.8±5.3)nmol·L-1.MCTP还可抑制ACh所致的胶原凝胶舒张,从(101.3±0.68)%减少到(94.1±0.77)%.结论MCTP可通过抑制CPAE的NO生成,影响肺动脉平滑肌的舒缩,可能是其导致肺动脉高压的一个因素.     

野百合碱对培养的肺动脉内皮细胞NO含量、eNOS蛋白表达及肺动脉平滑肌细胞收缩性的影响

目的研究野百合碱(monocrotaline pyrrole,MCTP)对培养的牛肺动脉内皮细胞(calf pulmonary artery endothelial cells,CPAEs)一氧化氮(NO)含量、内皮型一氧化氮合酶(eNOS)蛋白表达及肺动脉平滑肌细胞收缩的影响。方法采用荧光共聚焦激光显微镜检测培养的牛肺动脉内皮细胞的NO含量;Western blot检测eNOS蛋白表达;胶原凝胶实验分析肺动脉平滑肌细胞收缩性。结果经野百合碱处理的牛肺动脉内皮细胞NO含量和eNOS蛋白表达较对照组明显减少、肺动脉平滑肌细胞收缩性增强。结论MCTP可抑制eNOS蛋白表达,肺动脉内皮细胞NO产生受到抑制,使肺动脉平滑肌细胞收缩性增强,这些改变与肺动脉高压的形成可能存在一定关系。     

Synthesis and Kinetic Testing of Tetrahydropyrimidine-2-thione and Pyrrole Derivatives as Inhibitors of the Metallo-β-lactamase from Klebsiella pneumonia and Pseudomonas aeruginosa

Metallo‐β‐lactamases (MBLs), produced by an increasing number of bacterial pathogens, facilitate the hydrolysis of many commonly used β‐lactam antibiotics. There are no clinically useful antagonists against MBLs. Two sets of tetrahydropyrimidine‐2‐thione and pyrrole derivatives were synthesized and assayed for their inhibitory effects on the catalytic activity of the IMP‐1 MBL from Pseudomonas aeruginosa and Klebsiella pneumoniae. Nine compounds tested ( 1a , 3b , 5c , 6b , 7a , 8a , 11c , 13a , and 16a ) showed micromolar inhibition constants (K_i values range from ～20–80 μm ). Compounds 1c , 2b , and 15a showed only weak inhibition. In silico docking was employed to investigate the binding mode of each enantiomer of the strongest inhibitor, 5c (K_i = 19 ± 9 μm ), as well as 7a (K_i = 21 ± 10 μm ), the strongest inhibitor of the pyrrole series, in the active site of IMP‐1.     

聚吡咯膜电极氢功能

用电化学方法制备的聚吡咯膜电极经电化学处理得到具有氢功能的新型导电聚合物H~ 离子传感器,并研究了该膜电极的电化学性质,氢离子响应机制以及聚合条件和不同处理方法对电极电位响应性能的影响。该膜电极在pH3～12范围内对pH呈Nernst响应,电极系数为57mV/pH,对Li~ ,Na~ ,K~ 三种离子具有较高的抗干扰性。该电极具有内阻小,响应块,制备简便,响应范围宽等优点。     

Definitive diagnosis of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids

OBJECTIVE: Hepatic sinusoidal obstruction syndrome (HSOS) induced by a Chinese medicinal herb Tusanqi is increasingly being reported in recent years. The aim of the study was to investigate the possibility of using blood pyrrole‐protein adducts test as a confirmatory diagnostic method. METHODS: Patients with HSOS according to international diagnostic criteria associated with Tusanqi from January 2006 to August 2010 in Zhongshan Hospital Fudan University were included and clinical features were collected. Pyrrole‐protein adducts in blood sample were determined with ultra performance liquid chromatography‐mass spectrometry (UPLC‐MS) while pyrrolizidine alkaloids (PAs) in available herbal preparations were analyzed by high performance liquid chromatography‐ultraviolet (HPLC‐UV). RESULTS: Five patients (age 41–72 years, median age 54 years, all women) were included. Ascites (5/5), jaundice (5/5) and hepatomegaly (4/5) were common manifestations. The imaging features were diffused, patchy hepatic enhancement, periportal edema and ascites. Pathology ascertained that blood flow was obstructive at the site of sinusoid. PAs (Seneionine and seneciphylline) were identified in all the three available herbal preparations ingested by the HSOS patients. Pyrrole‐protein adducts were unequivocally found in all the five blood samples. Two patients recovered, two developed chronic illness and one died due to liver failure and hepatic encephalopathy. CONCLUSIONS: The detection of blood pyrrole‐protein adducts using a UPLC‐MS approach is a specific, reliable, unambiguous and confirmatory test for HSOS induced by PA, and should be used together with the conventional HSOS clinical diagnostic criteria for the definitive diagnosis of PA‐induced HSOS.     

抗干扰微型葡萄糖酶电极的研制

铂丝电极(长0．8cm，直径100μm)经铂化处理后，将3位取代的吡咯衍生物(3-羰基丁酸吡咯)与单体吡咯以适当的比例混合，与葡萄糖氧化酶(GOD)一起用循环伏安法电聚合到铂化的铂丝电极上，形成杂聚吡咯-GOD膜，制备成葡萄糖微酶电极。该微酶电极灵敏度高(每毫摩尔葡萄糖电流响应可以达到700nA)，响应范围大(0．1～110mmol／L)，抗干扰(抗坏血酸在该电极上的响应电流不到对比电极(无膜)的1．0％)，电极的稳定性良好，间断测定40d，灵敏度变化不大。     

Characterization and Properties of Poly[N‐(2‐cyanoethyl)pyrrole]

PNCPy was prepared by anodic polymerization and its properties in both doped and undoped state were characterized. The doping level of the oxidized material has been found to be larger than that of other conducting polymers; the more relevant electrochemical properties of the doped material were retained after undoping. SEM and AFM data are consistent with a lumpy surface and a multidirectional growing of the polymer chains. Finally, PNCPy has been combined with PEDOT to prepare three‐layer systems with enhanced electroactivity and electrostability. Results suggest that PNCPy is a potential candidate for the fabrication of electric circuit components that are able to block the current flow below a given potential.

     

Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines

Abstract:  Kynuramines represent their own class of biogenic amines. They are formed either by decarboxylation of kynurenines or pyrrole ring cleavage of indoleamines. N ²-formylated compounds formed in this last reaction can be deformylated either enzymatically by arylamine formamidases or hemoperoxidases, or photochemically. The earlier literature mainly focussed on cardiovascular effects of kynuramine, 5-hydroxykynuramine and their N ¹, N ¹-dimethylated analogs, including indirect effects via release of catecholamines or acetylcholine and interference with serotonin receptors. After the discovery of N ¹-acetyl- N ²-formyl-5-methoxykynuramine (AFMK) and N ¹-acetyl-5-methoxykynuramine (AMK) as major brain metabolites of melatonin, these compounds became of particular interest. They were shown to be produced enzymatically, pseudoenzymatically, by various free radical-mediated and via photochemical processes. In recent years, AFMK and AMK were shown to scavenge reactive oxygen and nitrogen species, thereby forming several newly discovered 3-indolinone, cinnolinone and quinazoline compounds, and to protect tissues from damage by reactive intermediates in various models. AMK is of special interest due to its properties as a potent cyclooxygenase inhibitor, NO scavenger forming a stable nitrosation product, inhibitor and/or downregulator of neuronal and inducible NO synthases, and a mitochondrial metabolism modulator. AMK easily interacts with aromates, forms adducts with tyrosyl and tryptophanyl residues, and may modify proteins.