An Easy Entry to Optically Active Spiroindolinones: Chiral Brønsted Acid‐Catalysed Pictet–Spengler Reactions of Isatins

The first catalytic asymmetric Pictet–Spengler reaction of isatins is presented. BINOL‐derived phosphoric acids were found to be competent catalysts for this transformation, giving challenging spirooxindole structures bearing a quaternary stereocentre with generally good results. The 1,2,3,4‐tetrahydro‐β‐carboline products (spiroindolinones) are the core of some newly discovered anti‐malarial agents.     

An investigation into transition metal ion binding properties of silk fibers and particles using radioisotopes

Silk is a structural protein fiber that is stable over a wide pH range making it attractive for use in medical and environmental applications. Variation in amino acid composition has the potential for selective binding for ions under varying conditions. Here we report on the metal ion separation potential of Mulberry and Eri silk fibers and powders over a range of pH. Highly sensitive radiotracer probes, ⁶⁴Cu²⁺, ¹⁰⁹Cd²⁺, and ⁵⁷Co²⁺ were used to study the absorption of their respective stable metal ions Cu²⁺, Cd²⁺, and Co²⁺ into and from the silk sorbents. The total amount of each metal ion absorbed and time taken to reach equilibrium occurred in the following order: Cu²⁺ > Cd²⁺ > Co²⁺. In all cases the silk powders absorbed metal ions faster than their respective silk fibers. Intensive degumming of the fibers and powders significantly reduced the time to absorb respective metal ions and the time to reach equilibrium was reduced from hours to 5–15 min at pH 8. Once bound, 45–100% of the metal ions were released from the sorbents after exposure to pH 3 buffer for 30 min. The transition metal ion loading capacity for the silk sorbents was considerably higher than that found for commercial ion exchange resins (AG MP‐50 and AG 50W‐X2) under similar conditions. Interestingly, total Cu²⁺ bound was found to be higher than theoretically predicted values based on known specific Cu²⁺ binding sites (AHGGYSGY), suggesting that additional (new) sites for transition metal ion binding sites are present in silk fibers. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Asymmetric Dimethylarginine Plasma Levels and Endothelial Function in Newly Diagnosed Type 2 Diabetic Patients

It is now well established that major risk factors for cardiovascular diseases (CVD) impact upon endothelial function by decreasing nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA), an endogenous analog of l-arginine, is able to inhibit the activity of endothelial-NO synthase, promoting endothelial dysfunction. Type 2 diabetes (T2D) is characterized by a reduced endothelium-dependent vasodilation and increased ADMA levels and ADMA is strongly associated with micro- and macrovascular diabetic complications. However, there are not a lot of data about the role of ADMA on endothelial function in newly diagnosed T2D patients without cardiovascular (CV) complications. For this aim, we have enrolled forty-five newly diagnosed T2D patients, evaluated by a oral glucose tolerance test, and thirty normal subjects. Endothelium-dependent and -independent vasodilatation was investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh) and sodium nitroprusside. ADMA was measured by high-performance liquid chromatography and insulin resistance (IR) by HOMA. Newly diagnosed T2D patients showed higher ADMA and l-arginine mean values in comparison with normal subjects and a significantly reduced ACh-stimulated forearm blood flow (FBF). In T2D patients FBF was significantly and inversely correlated with ADMA (r = −0.524, p < 0.0001) and in a multivariate regression analysis, ADMA resulted the stronger predictor of FBF, explaining the 27.5% of variability (p < 0.0001). In conclusion, ADMA was strongly related to endothelial dysfunction also in patients with newly diagnosed T2D, without clinically manifest vascular complications. This field is of great interest for understanding the mechanisms underlying the pathogenesis of diabetic disease and its CV complications.     

Peptidyl Vinyl Ketone Irreversible Inhibitors of Rhodesain: Modifications of the P2 Fragment

In this paper, we report the design, synthesis and biological investigation of a series of peptidyl vinyl ketones obtained by modifying the P2 fragment of previously reported highly potent inhibitors of rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense. Investigation of the structure–activity relationship led us to identify new rhodesain inhibitors endowed with an improved selectivity profile (a selectivity index of up to 22 000 towards the target enzyme), and/or an improved antitrypanosomal activity in the sub-micromolar range.     

Polyacrylamides revisited: flocculation of kaolin suspensions and mature fine tailings

A series of acrylamide‐based water‐soluble (co)polymers was synthesized and they were investigated as flocculants of model kaolin suspensions and mature fine tailings of oil sands. The effects of molar mass, charge density, and polymer concentration on flocculation efficiency were studied by monitoring the initial settling rate during sedimentation. Hydrolyzed polyacrylamide (HPAM) with high molar mass and intermediate acrylic acid contents (0.14–0.41 mol/mol (14–41 mol%)) performed better in flocculation tests on kaolin suspensions requiring lower dose for maximum initial settling rate than native polyacrylamide (PAM). Surface force measurements showed that at low polymer concentrations (1 ppm), the partially‐adsorbed polymer induced a bridging attraction between the mica surfaces. Increasing the polymer concentration to 10 and 50 ppm caused purely repulsive forces. The presence of anionic groups in HPAM led to stronger repulsion, which was also demonstrated by the higher viscosity and larger hydrodynamic radius of the charged polymer. The charge‐induced increase in the viscosity of polymer solutions was suppressed by the screening effect of salts in a buffer solution and reducing the viscosity is desirable in the injection of flocculants in the industrial process.     

Fish oil sensory properties can be predicted using key oxidative volatiles

The high level of PUFA in fish oil, primarily eicosapentaenoic acid (EPA) and DHA result in rapid oxidation of the oil. Current methods used to assess oxidation have little correlation with sensory properties of fish oils. Here we describe an alternative method using solid phase microextraction (SPME) combined with GC‐MS to monitor volatile oxidation products. Stepwise discriminant function analysis (DFA) was used to classify oils characterized as acceptable or unacceptable based on sensory analysis; a cross‐validated success rate of 100% was achieved with the function. The classification function was also successfully validated with tasted samples that were not used to create the method. A total of 14 variables, primarily aldehydes and ketones, were identified as significant discriminators in the classification function. This method will be useful as a quality control method for fish oil manufacturers. Practical applications: This paper describes an analytical method that can be used by fish oil manufacturers for quality control purposes. Solid phase microextraction and GC‐MS were used to monitor volatile oxidation products in fish oil. These data, combined with results of analyses by a sensory panel, were used to create a function that classified fish oil samples as acceptable or unacceptable. The volatile oxidation products used to in the function were primarily aldehydes and ketones. This method can be used by fish oil manufacturers as an alternative to expensive sensory panels.     

MT1‐Selective Melatonin Receptor Ligands: Synthesis,Pharmacological Evaluation,and Molecular Dynamics Investigation of N‐{[(3‐O‐Substituted)anilino]alkyl}amides

The design of compounds selective for the MT₁ melatonin receptor is still a challenging task owing to the limited knowledge of the structural features conferring selectivity for the MT₁ subtype, and only few selective compounds have been reported so far. N‐(Anilinoalkyl)amides are a versatile class of melatonin receptor ligands that include nonselective MT₁/MT₂ agonists and MT₂‐selective antagonists. We synthesized a new series of N‐(anilinoalkyl)amides bearing 3‐arylalkyloxy or 3‐alkyloxy substituents at the aniline ring, looking for new potent and MT₁‐selective ligands. To evaluate the effect of substituent size and shape on binding affinity and intrinsic activity, both flexible and conformationally constrained derivatives were prepared. The phenylbutyloxy substituent gave the best result, providing the partial agonist 4 a , which was endowed with high MT₁ binding affinity (pK_i=8.93) and 78‐fold selectivity for the MT₁ receptor. To investigate the molecular basis for agonist recognition, and to explain the role of the 3‐arylalkyloxy substituent, we built a homology model of the MT₁ receptor based on the β₂ adrenergic receptor crystal structure in its activated state. A binding mode for MT₁ agonists is proposed, as well as a hypothesis regarding the receptor structural features responsible for MT₁ selectivity of compounds with lipophilic arylalkyloxy substituents.     

Effects of protein properties on adsorption and transport in polymer‐grafted ion exchangers: A multiscale modeling study

We use multiscale modeling to study how the molecular properties of a protein affect its adsorption and transport in ion exchange chromatography matrices with either open pores or charged polymers grafted into the pore structure. Coarse‐grained molecular dynamics (MD) simulations of lysozyme, bovine serum albumin, and immunoglobulin show that higher protein net charge leads to greater partitioning into the polymer‐grafted pore space but slower diffusion there due to favorable electrostatic interactions, while larger size decreases both pore space partitioning and diffusion due to steric effects of the polymers. Mass transfer simulations based on the MD results show that the polymer‐grafted systems can enhance the adsorption kinetics if pore space partitioning and diffusion are both sufficiently high. The simulations illustrate that to achieve fast adsorption kinetics, there is a tradeoff between favorable binding and rapid diffusion which largely depends on the charge and size of the protein. © 2017 American Institute of Chemical Engineers AIChE J, 63: 4564–4575, 2017     

Production of renewable fuels by blending bio-oil with alcohols and upgrading under supercritical conditions

The work studied a non-catalytic upgrading of fast pyrolysis bio-oil by blending under supercritical conditions using methanol, ethanol and isopropanol as solvent and hydrogen donor. Characterisation of the bio-oil and the upgraded bio-oils was carried out including moisture content, elemental content, pH, heating value, gas chromatography-mass spectrometry (GCMS), Fourier transform infrared radiation, ¹³C nuclear magnetic resonance spectroscopy, and thermogravimetric analysis to evaluate the effects of blending and supercritical reactions. The GCMS analysis indicated that the supercritical methanol reaction removed the acids in the bio-oil consequently the pH increased from 2.39 in the crude bio-oil to 4.04 after the supercritical methanol reaction. The ester contents increased by 87.49% after the supercritical methanol reaction indicating ester formation could be the major deacidification mechanism for reducing the acidity of the bio-oil and improving its pH value. Simply blending crude bio-oil with isopropanol was effective in increasing the C and H content, reducing the O content and increasing the heating value to 27.55 from 17.51 MJ·kg^‒1 in the crude bio-oil. After the supercritical isopropanol reaction, the heating value of the liquid product slightly further increased to 28.85 MJ·kg^‒1.     

水泵水轮机泵工况下近设计点驼峰现象的流动机理研究*

中高比转速水泵水轮机泵工况下近设计点驼峰严重制约了其稳定运行范围,是制约抽水蓄能电站安全与经济运行的关键问题之一。作为流动问题的宏观表现,驼峰现象必然与水泵水轮机内部的非定常流动存在密切关系。为此,基于试验和数值模拟,对水泵水轮机泵工况下可调导叶流道内的非定常流动进行研究,探究模型机泵工况下的压力脉动特性、非定流动机理及与性能曲线稳定性之间的关系。结果表明：在设计和小于设计工况下,可调导叶流道内均存在两种显著的周期性压力脉动。模型机泵工况下的流量扬程曲线在0.45~0.75倍设计流量区间内出现驼峰,频域分析清晰地揭示了以上两种压力脉动是对该驼峰存在重要影响的流动参量。