Synthesis and structural characterization of high spin M/Cu (M = Mn, Fe) heterobimetallic and Fe/Cu2 trimetallic phosphinoamides

The heterobimetallic complexes [Mn((i)PrNPPh(2))(3)Cu((i)PrNHPPh(2))] (1) and [Fe((i)PrNPPh(2))(3)Cu((i)PrNHPPh(2))] (2) have been synthesized by the one pot reaction of LiN(i)PrPPh(2), MCl(2) (M = Mn, Fe), and CuI in high yield. Addition of excess CuI into 2 or directly to the reaction mixture led to the formation of a heterotrimetallic [Fe((i)PrNPPh(2))(3)Cu(2)((i)PrNPPh(2))] (3) in good yield. Complexes 1-3 have been characterized by means of elemental analysis, paramagnetic (1)H NMR, UV-vis spectroscopy, cyclic voltammetry, and single crystal X-ray analysis. In all three complexes, Mn or Fe are in the +2 oxidation state and have a high spin electron configuration, as evidenced by solution Evans' method. In addition, the oxidation state of Fe in complex 3 is confirmed by zero-field (57)Fe M?ssbauer spectroscopy. X-ray crystallography reveals that the three coordinate Mn/Fe centers in the zwitterionic complexes 1-3 adopt an unusual trigonal planar geometry.     

AlMe(3)-promoted formation of amides from acids and amines

In the presence of AlMe(3), amines can be directly coupled with acids through dimethylaluminum amide intermediates to form the corresponding amides. A wide range of amines and acids including less nucleophilic amines, bulky amines, unprotected secondary amino acids, and acids with poor solubility were coupled smoothly to give the desired products in 55-98% yields.     

Nanomechanical properties of single amyloid fibrils

Amyloid fibrils are traditionally associated with neurodegenerative diseases like Alzheimer's disease, Parkinson's disease or Creutzfeldt-Jakob disease. However, the ability to form amyloid fibrils appears to be a more generic property of proteins. While disease-related, or pathological, amyloid fibrils are relevant for understanding the pathology and course of the disease, functional amyloids are involved, for example, in the exceptionally strong adhesive properties of natural adhesives. Amyloid fibrils are thus becoming increasingly interesting as versatile nanobiomaterials for applications in biotechnology. In the last decade a number of studies have reported on the intriguing mechanical characteristics of amyloid fibrils. In most of these studies atomic force microscopy (AFM) and atomic force spectroscopy play a central role. AFM techniques make it possible to probe, at nanometer length scales, and with exquisite control over the applied forces, biological samples in different environmental conditions. In this review we describe the different AFM techniques used for probing mechanical properties of single amyloid fibrils on the nanoscale. An overview is given of the existing mechanical studies on amyloid. We discuss the difficulties encountered with respect to the small fibril sizes and polymorphic behavior of amyloid fibrils. In particular, the different conformational packing of monomers within the fibrils leads to a heterogeneity in mechanical properties. We conclude with a brief outlook on how our knowledge of these mechanical properties of the amyloid fibrils can be exploited in the construction of nanomaterials from amyloid fibrils.     

Tri- and Pentamethine Cyanine Dyes for Fluorescent Detection of α-Synuclein Oligomeric Aggregates

The pathogenesis of Parkinson’s disease that is the second most common neurodegenerative disease is associated with formation of different aggregates of α-synuclein (ASN), namely oligomers and amyloid fibrils. Current research is aimed on the design of fluorescent dyes for the detection of oligomeric aggregates, which are considered to be toxic and morbific spices. Fluorescent properties of series of benzothiazole trimethine and pentamethine cyanines were characterized in free state and in presence of monomeric, oligomeric and fibrilar ASN. The dyes with wide aromatic systems and bulky phenyl and alkyl substituents that are potentially able to interact with hydrophobic regions of oligomeric aggregates were selected for the studies. For majority of studied dyes noticeable changes in fluorescence characteristics were shown in the presence of fibrillar or oligomeric ASN, while the dyes slightly responded on the presence of monomeric protein. For pentamethine cyanine SL-631 and trimethine cyanine SH-299 certain specificity to oligomeric aggregates over fibrils was observed. Using these dyes at 10^?6 M concentration permits the detection of oligomeric ASN in the concentrations range of at least 0.2–2 microM. Pentamethine cyanine SL-631 is proposed as dye for fluorescent detection of oligomeric aggregates of ASN, while trimethine cyanine SH-299 is shown to be a sensitive probe both on oligomeric and fibrillar ASN. It is proposed that wide aromatic system of SL-631 pentamethine dye molecule could better fix on the less dense and structured oligomeric formation, while less bulky and more “crescent-shape” molecule of trimethine dye SH-299 could easier enter into the groove of beta-pleated structure.     

Synthesis of first ever 4-quinolone-3-carboxylic acid-appended spirooxindole-pyrrolidine derivatives and their biological applications

A series of 4-quinolone-3-carboxylic acid-containing spirooxindole-pyrrolidine derivatives was synthesized via multicomponent 1,3-dipolar cycloaddition reactions of azomethine ylides with new (E)-4-oxo-6-(3-phenyl-acryloyl)-1,4-dihydroquinoline-3-carboxylic acids in good yields with high regioselectivity. The cycloadducts were characterized by analytical and spectral data including \(^{1}\hbox {H}\), \(^{13}\hbox {C}\), 2D NMR and mass spectroscopy. The structure of one of the compounds (8a) was investigated theoretically by computational techniques. DFT studies support the proposed mechanism for this cycloaddition reaction. Furthermore, antibacterial activities of the new compounds were evaluated against Gram-positive and Gram-negative bacterial strains. Compounds 8f, 8m and 8p showed potent inhibition activities against selected bacteria. The in vitro cytotoxicity of spirooxindole derivatives (8a–r) was evaluated against MCF-7 breast cancer cell line. Among the various compounds tested, compound 8f \((\hbox {IC}_{50} = 18.35~\upmu \hbox {M})\) showed significant cytotoxic activity compared to the standard drug doxorubicin \((\hbox {IC}_{50 }= 15.00~\upmu \hbox {M})\).     

Effect of Particle Clusters on Carrier Flow Turbulence: A Direct Numerical Simulation Study

Experiments indicate that particle clusters that form in fluidized–bed risers can enhance gas-phase velocity fluctuations. Direct numerical simulations (DNS) of turbulent flow past uniform and clustered configurations of fixed particle assemblies at the same solid volume fraction are performed to gain insight into particle clustering effects on gas-phase turbulence, and to guide model development. The DNS approach is based on a discrete-time, direct-forcing immersed boundary method (IBM) that imposes no-slip and no-penetration boundary conditions on each particle’s surface. Results are reported for mean flow Reynolds number Re _p ?=?50 and the ratio of the particle diameter d _p to Kolmogorov scale is 5.5. The DNS confirm experimental observations that the clustered configurations enhance the level of fluid-phase turbulent kinetic energy (TKE) more than the uniform configurations, and this increase is found to arise from a lower dissipation rate in the clustered particle configuration. The simulations also reveal that the particle-fluid interaction results in significantly anisotropic fluid-phase turbulence, the source of which is traced to the anisotropic nature of the interphase TKE transfer and dissipation tensors. This study indicates that when particles are larger than the Kolmogorov scale (d _p ?>?η), modeling the fluid-phase TKE alone may not be adequate to capture the underlying physics in multiphase turbulence because the Reynolds stress is anisotropic. It also shows that multiphase turbulence models should consider the effect of particle clustering in the dissipation model.     

100 W Kinetically enhanced copper vapor laser at 10 kHz repetition-rate, high (∼1.5%) efficiency with low (∼1.6 kW/l) specific input power and performance of new resonator configurations

It is established here that kinetically enhanced copper vapor lasers (KE-CVLs) based on large-bore discharge tubes can provide high (>1.4%) efficiency at ∼9-10 kHz rep-rate with very low (<2 kW/l) specific input power. Comparative performance of various large-bore kinetically enhanced copper vapor lasers in the range 45-70 mm is presented for most suitable discharge tube. Maximum output power of ∼100 W was achieved with efficiency of about 1.55% at 10 kHz rep-rate from the 60 mm bore KE-CVL. The pulse to pulse efficiency of the KE-CVL was ∼2%, tube efficiency ∼2.1%, and laser pulse energy was about ∼10 mJ. These results show significant advancement in the laser system as an elemental high temperature CVL due to volumetric scaling and KE-effects combined with very low specific input power of ∼1.65 kW/l as compared to 8-9 kW/l normally required in other kinetically enhanced copper vapor lasers to generate ∼100 W output power. Performance of the KE-CVL with 3 new cavity configurations namely, (1) CAT-EYE resonator (2) hybrid resonator, and (3) modified diffraction coupled resonator with dot mirrors are presented for the first here. CAT-EYE resonator was demonstrated to achieve high misalignment tolerance without significant loss of power. A typical drift in power of ∼5% was observed with misalignment responsible for 40% decline in power in case of standard plane-plane cavity. Effect of resonator misalignment on amplifier output drift was also investigated using CAT-EYE resonator in oscillator-amplifier configuration. In case of using stable-unstable hybrid resonator, high magnification of M ∼ 1500 was realized resulting in extremely low divergence (∼0.08 mrad) beam with modest (∼20%) loss in average power. In case of modified DCR cavity, record power of about 48 W was achieved with beam divergence of about 0.1 mrad on using intra-cavity 2 × 2 array of 4 dot mirrors.     

Regioselective alkylation reactions of 2,4-diphenyl-3H-1-benzazepine give either 3-alkyl-3H-1-benzazepines or 1-alkyl-1H-1-benzazepines

2,4-Diphenyl-3H-1-benzazepine is deprotonated with either LDA or KHMDS. The resulting anion is alkylated with alkyl halides or MeOTs, giving either products of alkylation at C3, or at N, or a mixture of both. The regioselectivity depends on the base, presence of the complexing agent HMPA, and the leaving group of the alkylating agent. Using MeI as alkylating agent gives exclusively the C3-methylated product, while using MeOTs gives exclusively the N-methylated product. The N-alkylated products show evidence of stereodynamic behavior in their NMR spectra.