Studies on Performance of Cellulose Acetate and Poly(Ethelene Glycol) Blend Ultrafiltration Membranes Using Mixture Design Concept of Design of Experiments

Cellulose acetate (CA) membranes have several advantages over other membranes due to their moderate flux, high salt rejection properties, renewable source of raw material, etc. Membrane compositions containing different concentrations of CA, polyethylene glycol (PEG 600) as additive and N,N–dimethyl formamide (DMF) as solvent have been prepared using phase inversion technique based on the mixture design concept of design of experiments. The prepared membranes have been characterized for permeate flux, membrane hydraulic resistance, and separation of proteins such as pepsin, egg albumin (EA), and bovine serum albumin (BSA). Using statistical techniques, the experimental data have been analyzed and a suitable model was suggested for predicting the optimal level of response as a function of the input variable. The influence of variation of the CA, DMF, and PEG 600 on the asymmetric membrane properties has also been reported.     

细胞周期蛋白依赖性激酶抑制剂（CDKs）中间体的设计与合成

简述了细胞周期蛋白依赖性激酶CDK4抑制剂及其抑制剂的相关概念,详细介绍了细胞周期蛋白激酶的研究进展,重点研究了中间体2一溴-1-（4-吗啉苯基）乙酮的路线选择与合成。4-氟苯乙酮为起始原料,经过溴代反应合成2-溴-1-（4-吗啉苯基）乙酮。依据文献报道,比较不同的合成路线,最终选择先溴代再脱溴的方法合成目标化合物。     

Design,Synthesis, Molecular Modeling and Anti-Hyperglycemic Evaluation of Quinazoline-Sulfonylurea Hybrids as Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) and Sulfonylurea Receptor (SUR) Agonists

New quinazoline-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds VI-6-a, V, IV-4, VI-4-c, IV-6, VI-2-a, IV-1, and IV-2 were more potent than the reference glibenclamide. They induced significant reduction in the blood glucose levels of diabetic rats: 78.2, 73.9, 71.4, 67.3, 62, 60.7, 58.4, and 55.9%, respectively, while the reference glibenclamide had 55.4%. Compounds IV-1, VI-2-a, IV-2, V, and IV-6 showed more prolonged antidiabetic activity than glibenclamide. Moreover, molecular docking and pharmacokinetic studies were performed to examine binding modes of the prepared compounds against peroxisome proliferator-activated receptor gamma (PPARγ). The highest active compounds exhibited good binding affinity with high free energy of binding against PPARγ. In silico absorption, distribution, metabolism, elimination and toxicity (ADMET) studies were performed to investigate pharmacokinetics and safety of the synthesized compounds. They showed considerable human intestinal absorption with low toxicity profile.     

N-苯基-3-氯-6-(3,5-二甲基-1-吡唑基)吡啶-2-甲酰胺及3-氯-6-(3,5-二甲基-1-吡唑基)吡啶-2-甲酸的合成和表征

以3,6-二氯吡啶-2-甲酸为原料经过酰胺化、肼取代、环合、水解等反应合成了标题化合物,并通过红外光谱、核磁共振谱和质谱对其结构进行了表征.     

Integration of Design and Control: A Robust Control Approach Using MPC

This paper presents a new method to integrate process control with process design. The process design is based on steady‐state costs, .i.e., capital and operating costs. Control is incorporated into the design in terms of a variability cost. This term is calculated based on the non‐linear process model, represented here as a nominal linear model supplemented with model parameter uncertainty. Robust control tools are then used within the approach to assess closed‐loop robust stability and to calculate closed‐loop variability. The integrated method results in a non‐linear constrained optimization problem with an objective function that consists of the sum of the steady costs and the variability cost. Optimization using the traditional sequential approach and the new integrated method was applied to design a multi‐component distillation column using a Model Predictive Control (MPC) algorithm. The optimization results show that the integrated method can lead to significant cost savings when compared to the traditional sequential approach. In addition, an RGA analysis was performed to study the effects of process interactions on the optimization results.     

Inhibitors of Polyhydroxyalkanoate (PHA) Synthases: Synthesis,Molecular Docking,and Implications

Polyhydroxyalkanoate (PHA) synthases (PhaCs) catalyze the formation of biodegradable PHAs that are considered to be ideal alternatives to non‐biodegradable synthetic plastics. However, study of PhaCs has been challenging because the rate of PHA chain elongation is much faster than that of initiation. This difficulty, along with lack of a crystal structure, has become the main hurdle to understanding and engineering PhaCs for economical PHA production. Here we report the synthesis of two carbadethia CoA analogues—sT‐CH₂‐CoA ( 26 a ) and sTet‐CH₂‐CoA ( 26 b )—as well as sT‐aldehyde (saturated trimer aldehyde, 29 ), as new PhaC inhibitors. Study of these analogues with PhaEC_Av revealed that 26 a / b and 29 are competitive and mixed inhibitors, respectively. Both the CoA moiety and extension of PHA chain will increase binding affinity; this is consistent with our docking study. Estimation of the K_ic values of 26 a and 26 b predicts that a CoA analogue incorporating an octameric hydroxybutanoate (HB) chain might facilitate the formation of a kinetically well‐behaved synthase.     

关于创新型毕业设计(论文)模式的研究探索

毕业设计是本科教育阶段历时最长、层次最高、综合性最强、最接近工程实际的实践性教学环节,是高校本科教学质量评估的一项重要内容。通过对近三年本科生毕业设计的研究与探索中,提出了创新型的毕业设计模式,即采用导师、工程师、实践单位与学生相结合的"三位一体"模式,极大地调动了学生学习积极性和能动性,有效地提高了教学质量和学生的工程设计能力。     

A New Route to Perfluoro(Propyl Vinyl Ether) Monomer: Synthesis of Perfluoro(2‐propoxypropionyl) Fluoride from Non‐Fluorinated Compounds

Perfluoro(2‐propoxypropionyl) fluoride ( 1a ), which is the precursor of the perfluorinated propyl vinyl ether (PPVE) monomer of an industrially important perfluoroalkoxy copolymer (PFA), was synthesized by utilizing direct fluorination of the non‐fluorinated counterpart for the first time. The partially‐fluorinated ester 7 synthesized from the desired perfluorinated acid fluoride 1a itself and the non‐fluorinated alcohol 5 , which has a carbon skeleton corresponding to the desired compound 1a , was perfluorinated by liquid‐phase direct fluorination with elemental fluorine. Degradation of the resulting perfluorinated ester 8 gave 2 mols of the desired acid fluoride 1a . In a sense, this process can be called self‐multiplication of a perfluorinated acid fluoride from a non‐fluorinated alcohol.     

年产15万吨"双甲"精制氨合成高压圈的设计与运行

把“双甲”精制工艺与氨合成组成高压圈，介绍年产15万吨精制氨合成高压圈工艺，阐述了工艺流程、主要设备和设计总目标，对生产运行中各系统参数和经济效益进行了总结。     

Design,Synthesis and Anticancer Profile of New 4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine-Linked Sulfonamide Derivatives with V600EBRAF Inhibitory Effect

A new series of 4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine linked sulfonamide derivatives 12a–n was designed and synthesized according to the structure of well-established V600EBRAF inhibitors. The terminal sulfonamide moiety was linked to the pyrimidine ring via either ethylamine or propylamine bridge. The designed series was tested at fixed concentration (1 µM) against V600EBRAF, finding that 12e, 12i and 12l exhibited the strongest inhibitory activity among all target compounds and 12l had the lowest IC₅₀ of 0.49 µM. They were further screened on NCI 60 cancer cell lines to reveal that 12e showed the most significant growth inhibition against multiple cancer cell lines. Therefore, cell cycle analysis of 12e was conducted to investigate the effect on cell cycle progression. Finally, virtual docking studies was performed to gain insights for the plausible binding modes of vemurafenib, 12i, 12e and 12l.     

N‐(Anilinoethyl)amides: Design and Synthesis of Metabolically Stable,Selective Melatonin Receptor Ligands

The class of N‐(anilinoethyl)amides includes melatonin receptor ligands with varied subtype selectivity and intrinsic activity. One of these ligands, the MT₂‐selective partial agonist UCM765 (N‐{2‐[(3‐methoxyphenyl)phenylamino]ethyl}acetamide), had evidenced hypnotic effects in rodents at doses ≥40 mg kg^?1 (s.c.), in spite of its sub‐nanomolar affinity for human melatonin receptors. Supposing that its low in vivo potency could be due, at least in part, to metabolic liability in rat liver, UCM765 was incubated with rat liver S9 fraction and rat, mouse, or human microsomes, and the major metabolites were identified by LC–MS, synthesized, and in vitro tested for their affinity toward MT₁ and MT₂ receptors. The obtained information was exploited to design novel analogues of UCM765 that are more resistant to in vitro oxidative degradation, while maintaining a similar binding profile. The analogue UCM924 (N‐{2‐[(3‐bromophenyl)‐(4‐fluorophenyl)amino]ethyl}acetamide) displayed a binding profile similar to that of UCM765 on cloned human receptors (MT₂‐selective partial agonist) and a significantly longer half‐life in the presence of rat liver S9 fraction.     

Design and Synthesis of Ionic Liquid-Based Matrix Metalloproteinase Inhibitors (MMPIs): A Simple Approach to Increase Hydrophilicity and to Develop MMPI-Coated Gold Nanoparticles

Selective and potent matrix metalloproteinase 12 (MMP-12) inhibitors endowed with improved hydrophilicity are highly sought for potential use in the treatment of lung and cardiovascular diseases. In the present paper, we modified the structure of a nanomolar MMP-12 inhibitor by incorporating an ionic liquid (IL) moiety to improve aqueous solubility. Four biologically active salts were obtained by linking the sulfonamide moiety of the MMP-12 inhibitor to imidazolium-, pyrrolidinium-, piperidinium-, and DABCO-based ILs. The imidazolium-based bioactive salt was tested on human recombinant MMPs and on monocyte-derived dendritic cells, showing activity similar to that of the parent compound, but improved water solubility. The imidazolium-based bioactive salt was then used to prepare electrostatically stabilized MMP inhibitor-coated gold nanoparticles (AuNPs) able to selectively bind MMP-12. These AuNPs were used to study subcellular localization of MMP-12 in monocyte-derived dendritic cells by transmission electron microscopy analysis.     

Cover Picture: A Cyclic CCK8 Analogue Selective for the Cholecystokinin Type A Receptor: Design,Synthesis, NMR Structure and Binding Measurements (ChemBioChem 11/2003)

The cover picture shows a molecular model of the interaction between the new CCK8 analogue, Cycle29,34[Dpr29,Lys34]‐CCK8 (shown as a CPK model) and the receptor fragment CCK_A‐R(1–47) (represented by a pink ribbon). The introduction of the cyclic constraint between the Dpr29 sidechain and the CCK8 C terminus (Lys34) decreases the flexibility of the molecule to stabilize the bioactive conformation of Cycle29,34[Dpr29,Lys34]‐CCK8. The Trp30 and Met31 side chains are in favorable orientations for interaction with the CCKA receptor. Expansions of the aromatic/amide regions of the ¹H NMR spectra of Cycle29,34[Dpr29,Lys34]‐CCK8 in aqueous solution (top) and in presence of dodecylphosphocholine‐d₃₈ micelles (bottom) are shown in the inset. Further details can be found in the article by Morelli and co‐workers on p. 1176 ff.     

Iron(III) Chloride‐Catalyzed Decarboxylative–Deaminative Functionalization of Phenylglycine: A Tandem Synthesis of Quinazolinones and Benzimidazoles

The first iron(III) chloride‐catalyzed decarboxylative–deaminative functionalization of phenylglycine with o‐substituted nitroarenes was achieved for the synthesis of 4(3H)‐quinazolinones and benzimidazoles. The reaction of 2‐nitrobenzonitrile/2‐nitro‐N,N‐diphenylamine with phenylglycine at 120 °C in the presence of potassium carbonate as a base in toluene generated the products in 45–87% yields. Various functional groups like nitro, fluoride, chloride and trifluoromethyl were well tolerated under the present reaction conditions. In this tandem approach, involvement of transfer hydrogenation of the nitro functionality with in situ generated ammonia, imination, nitrile hydration to amide and oxidative cyclization sequences have been established. The process avoids the use of an external hydrogen source, costly catalysts as well as the isolation of amine and amide intermediates.