Organic–inorganic nanomatrix structure and properties of related naturally occurring rubbery macromolecules

The outstanding mechanical properties of soft materials i.e. natural rubber are partly due to the organic–inorganic nanomatrix structure because numerous organic microparticles are dispersed in a small amount of an inorganic nanomatrix composed of inorganic nanoparticles and organic macromolecules. Here we form an organic–inorganic nanomatrix using graft-copolymerization of a vinyl monomer with an inorganic oxide precursor onto natural rubber particles with an average diameter of 1 μm dispersed in water. The inorganic oxide precursor is converted into inorganic oxide nanoparticles through hydrolysis and condensation, forming chemical linkages between natural rubber microparticles and inorganic oxide nanoparticles. Transmission electron microscopy indicates that the organic–inorganic nanomatrix is densely filled with inorganic oxide nanoparticles and the natural rubber microparticles are dispersed in the nanomatrix. This nanomatrix composite realizes both energetic elasticity and entropic elasticity of a soft material, opening a novel field of building block chemistry with respect to a pair of organic microparticles and inorganic nanoparticles.     

The first naturally occurring α-methoxylated branched-chain fatty acids from the phospholipids of Amphimedon complanata

The phospholipid fatty acid composition of the sponge Amphimedon complanata was reinvestigated, and the 2-methoxy-13-methyltetradecanoic acid, 2-methoxy-14-methylpentadecanoic acid, and 2-methoxy-13-methylpentadecanoic acid were identified for the first time in nature. Structure characterization was accomplished by means of gas chromatographic retention times and gas chromatography-mass spectrometry. These acids could have originated from bacteria in symbiosis with the sponge.     

The heterogeneous nature of Cu2+ interactions with Alzheimer's amyloid-β peptide

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive and memory impairment. Within the brain, senile plaques, which comprise extracellular deposits of the amyloid-β peptide (Aβ), are the most common pathological feature of AD. A high concentration of Cu(2+) is found within these plaques, which are also areas under oxidative stress. Laboratory work has shown that in vitro Aβ will react with Cu(2+) to induce peptide aggregation and the production of reactive oxygen species. As such, this interaction offers a possible explanation for two of the defining pathological features observed in the AD brain: the presence of amyloid plaques, which consist largely of insoluble Aβ aggregates, and the abundant oxidative stress therein. Researchers have accordingly put forth the "metals hypothesis" of AD, which postulates that compounds designed to inhibit Cu(2+)/Aβ interactions and redistribute Cu(2+) may offer therapeutic potential for treating AD. Characterization of the pH-dependent Cu(2+) coordination of Aβ is fundamental to understanding the neurological relevance of Cu(2+)/Aβ interactions and aiding the design of new therapeutic agents. In an effort to shed light on the problem, many experimental and theoretical techniques, using a variety of model systems, have been undertaken. The preceding decade has seen numerous conflicting spectroscopic reports concerning the nature of the Cu(2+)/Aβ coordination. As the number of studies has grown, the nature of the pH-dependent ligand environment surrounding the Cu(2+) cation has remained a point of contention. In large part, the difficulties can be attributed to inappropriate choices of the model system or to methods that are incapable of quantitatively delineating the presence and identity of multiple Cu(2+) coordination modes. Electron paramagnetic resonance (EPR) is the method of choice for studying paramagnetic metal-protein interactions. With the introduction of site-specific (15)N, (17)O, and (13)C isotopic labels and the application of advanced techniques, EPR is capable of eliminating much of the ambiguity. Recent EPR studies have produced the most definitive picture of the pH-dependent Cu(2+) coordination modes of Aβ and enabled researchers to address the inconsistencies present in the literature. In this Account, we begin by briefly introducing the evidence for a role of Cu(2+) in AD as well as the potential physiological and therapeutic implications of that role. We then outline the EPR methodology used to resolve the molecular details of the Cu(2+)/Aβ interactions. No drugs are currently available for altering the course of AD, and existing therapies only offer short-term symptomatic relief. This focused picture of the role of Cu(2+) in AD-related plaques offers welcome potential for the development of new methods to combat this devastating disease.     

Chirality Dependence of Amyloid β Cellular Uptake and a New Mechanistic Perspective

Amyloid β is an inherently disordered peptide that can form diverse neurotoxic aggregates, and its 42-amino-acid isoform is believed to be the agent responsible for Alzheimer's disease (AD). Cellular uptake of the peptide is a pivotal step for it to be able to exert many of its toxic actions. The cellular uptake process is complex, and numerous competing internalization pathways have been proposed. To date, it remains unclear which of the uptake mechanisms are particularly important for the overall process, and improvement of this understanding is needed, so that better molecular AD therapeutics can be designed. Chirality can be used as a unique tool to study this process, because some of the proposed mechanisms are expected to proceed in stereoselective fashion, whereas others are not. To shed light on this important issue, we synthesized fluorescently labeled enantiomers of amyloid β and quantified their cellular uptake, finding that uptake occurs in stereoselective fashion, with a typical preference for the l stereoisomer of ≈5:1. This suggests that the process is predominantly receptor-mediated, with likely minor contributions of non-stereoselective mechanisms.     

Structures and Functions of Qβ Replicase: Translation Factors beyond Protein Synthesis

Qβ replicase is a unique RNA polymerase complex, comprising Qβ virus-encoded RNA-dependent RNA polymerase (the catalytic β-subunit) and three host-derived factors: translational elongation factor (EF) -Tu, EF-Ts and ribosomal protein S1. For almost fifty years, since the isolation of Qβ replicase, there have been several unsolved, important questions about the mechanism of RNA polymerization by Qβ replicase. Especially, the detailed functions of the host factors, EF-Tu, EF-Ts, and S1, in Qβ replicase, which are all essential in the Escherichia coli (E. coli) host for protein synthesis, had remained enigmatic, due to the absence of structural information about Qβ replicase. In the last five years, the crystal structures of the core Qβ replicase, consisting of the β-subunit, EF-Tu and Ts, and those of the core Qβ replicase representing RNA polymerization, have been reported. Recently, the structure of Qβ replicase comprising the β-subunit, EF-Tu, EF-Ts and the N-terminal half of S1, which is capable of initiating Qβ RNA replication, has also been reported. In this review, based on the structures of Qβ replicase, we describe our current understanding of the alternative functions of the host translational elongation factors and ribosomal protein S1 in Qβ replicase as replication factors, beyond their established functions in protein synthesis.     

Thiophene-Based Dual Modulators of Aβ and Tau Aggregation

Alzheimer's disease is characterized by the accumulation of amyloid beta (Aβ) and Tau aggregates in the brain, which induces various pathological events resulting in neurodegeneration. There have been continuous efforts to develop modulators of the Aβ and Tau aggregation process to halt or modify disease progression. A few small-molecule-based inhibitors that target both Aβ and Tau pathology have been reported. Here, we report the screening of a targeted library of small molecules to modulate Aβ and Tau aggregation together with their in vitro, in silico and cellular studies. In vitro ThT fluorescence assay, dot blot assay, gel electrophoresis and transmission electron microscopy (TEM) results have shown that thiophene-based lead molecules effectively modulate Aβ aggregation and inhibit Tau aggregation. In silico studies performed by employing molecular docking, molecular dynamics and binding-free energy calculations have helped in understanding the mechanism of interaction of the lead thiophene compounds with Aβ and Tau fibril targets. In cellulo studies revealed that the lead candidate is biocompatible and effectively ameliorates neuronal cells from Aβ and Tau-mediated amyloid toxicity.     

Failure,Success, and Future Direction of Alzheimer Drugs Targeting Amyloid-β Cascade: Pros and Cons of Chemical and Biological Modalities

Alzheimer's disease (AD) is the most prevalent cause of dementia and has become a health concern worldwide urging for an effective therapeutic. The amyloid hypothesis, currently the most pursued basis of AD drug discovery, points the cause of AD to abnormal production and ineffective removal of pathogenic aggregated amyloid-β (Aβ). AD therapeutic research has been focused on targeting different species of Aβ in the amyloidogenic process to control Aβ content and recover cognitive decline. Among the different processes targeted, the clearance mechanism has been found to be the most effective, supported by the recent clinical approval of an Aβ-targeting immunotherapeutic drug which significantly slowed cognitive decline. Although the current AD drug discovery field is extensively researching immunotherapeutic drugs, there are numerous properties of immunotherapy in need of improvements that could be overcome by an equally performing chemical drug. Here, we review chemical and immunotherapy drug candidates, based on their mechanism of modulating the amyloid cascade, selected from the AlzForum database. Through this review, we aim to summarize and evaluate the prospect of Aβ-targeting chemical drugs.     

Formaldehyde-Crosslinked Nontoxic Aβ Monomers to Form Toxic Aβ Dimers and Aggregates: Pathogenicity and Therapeutic Perspectives

Alzheimer's disease (AD) is characterized by the presence of senile plaques in the brain. However, medicines targeting amyloid-beta (Aβ) have not achieved the expected clinical effects. This review focuses on the formation mechanism of the Aβ dimer (the basic unit of oligomers and fibrils) and its tremendous potential as a drug target. Recently, age-associated formaldehyde and Aβ-derived formaldehyde have been found to crosslink the nontoxic Aβ monomer to form the toxic dimers, oligomers and fibrils. Particularly, Aβ-induced formaldehyde accumulation and formaldehyde-promoted Aβ aggregation form a vicious cycle. Subsequently, formaldehyde initiates Aβ toxicity in both the early-and late-onset AD. These facts also explain why AD drugs targeting only Aβ do not have the desired therapeutic effects. Development of the nanoparticle-based medicines targeting both formaldehyde and Aβ dimer is a promising strategy for improving the drug efficacy by penetrating blood-brain barrier and extracellular space into the cortical neurons in AD patients.     

The synthesis of novel perylene-like dyes and their aggregation properties in Langmuir and Langmuir–Blodgett films

The synthesis of novel perylene-like dyes with different length and molecular structure of terminal chains substituted to the main perylene core is described. The dyes are able to form compressible and stable monolayers at the air–water interface (Langmuir films), which can be easily transferred onto solid substrates (Langmuir–Blodgett films). In the Langmuir and Langmuir–Blodgett films, the dye molecules show tendency to creation of self-aggregates, both in the ground and excited electronic states. The influence of the molecular structure of the substituents on the aggregation properties is observed and discussed.     

Wavelength dependence of Kubelka–Munk scattering spectra for studies of TiO2 microstructure and aggregation in paints

The wavelength exponent β is easily determined from diffuse reflectance spectra as the gradient of a log–log plot of the Kubelka–Munk scattering coefficient (S) against wavelength. Previous work suggests that β provides a useful relative measure of the size of scattering units applicable to many particulate systems. This article examines the applicability of β to paints, specifically studies of TiO₂ aggregation, and comments on its wider use for pigmented coatings. Modelling using multisphere T-matrix Mie methods shows that β varies nearly linearly with the mean aggregate size. Experimental data shows good correlation between the state of aggregation and β. However, β depends strongly on the volume fraction of TiO₂ owing to the effects of dependent scattering arising from crowding, therefore comparisons between paints can only be made at constant effective TiO₂ volume fraction. A simple effective medium refractive index model in conjunction with Mie scattering appears to give a good account of the behavior of both S and β with increasing TiO₂ volume concentration. When air is incorporated into the coatings at high pigment volume fractions, scattering is much more complicated. In this case it appears very difficult to relate β directly to coating microstructure properties such as pore diameter.     

Regioselective nitration of toluene to para-nitrotoluene with NO2 over dealumination Hβ zeolite: Comparison of organic and inorganic acids

This work presents a novel heterogeneous catalytic system for the preparation of para-nitrotoluene (p-NT) with nitrogen dioxide (NO₂) as a nitrating agent in the presence of oxygen (O₂). By applying dealuminated Hβ zeolite treated with oxalic acid (Hβ-Ox) as a catalyst, p-NT can be obtained with high conversion (90.5%) and selectivity (72.6%). In addition, it can be recycled at least five times without a significant decrease in catalytic activity. This result demonstrates that the catalyst has high efficiency, good stability, and regenerability. Meanwhile, the characteristics of pristine Hβ and different dealuminated Hβ zeolites modified with organic and inorganic acids were systematic contrastive studied using X-ray diffraction (XRD), nitrogen (N₂) adsorption-desorption, Fourier-transform infrared (FT-IR), scanning electron microscope (SEM), temperature-programed desorption of ammonia (NH₃-TPD), pyridine adsorption infrared (Py-FT-IR), and solid state ²⁷Al nuclear magnetic resonance (²⁷Al MAS-NMR). Finally, the higher conversion and para-selectivity over Hβ-Ox also give a reasonable explanation in this paper.     

Synthesis and Interface Activity of a Series of Dicarboxylic Cationic Surfactants and a Structure–Efficiency Relationship Study

Quaternary ammonium cationic surfactants are widely used in many fields, but information about the effect of the anion on cationic surfactants is scarce. To study the effect of anions on the surface properties, six dicarboxylic cationic surfactants were prepared, (cetyltrimethylammonium oxalate, CTAO; cetyltrimethylammonium malonate, CTAM; cetyltrimethylammonium succinate, CTASU; cetyltrimethylammonium glutarate, CTAG; cetyltrimethylammonium adipate, CTAA; and cetyltrimethylammonium sebacate, CTASE), and their surface properties were studied, including surface tension, critical micelle concentration, foaming ability and stability, and corrosion inhibition. The results showed that the minimum surface tension followed the order of CTAO<CTAM<CTASU<CTAG<CTAA<CTASE. The foaming ability followed the order of CTAO>CTAM>CTASU>CTAG>CTAA>CTASE. The foaming stability followed the order of CTAM>CTAO>CTASU>CTAG>CTAA>CTASE. At a concentration of 1.0 g L⁻¹, the order of emulsification power of these surfactants was CTASE<CTAO<CTAA<CTAG<CTASU<CTAM, and at 5.0 g L⁻¹, the order was CTASE<CTASU<CTAA<CTAG<CTAO<CTAM. The corrosion inhibition efficiency on mild steel followed the order of CTASE<CTAA<CTAG<CTASU<CTAM<CTAO.     

Sol–gel synthesis,characterization, and neurotoxicity effect of zinc oxide nanoparticles using gum tragacanth

The use of plant extract in the synthesis of nanomaterials can be a cost effective and eco-friendly approach. In this work we report the “green” and biosynthesis of zinc oxide nanoparticles (ZnO-NPs) using gum tragacanth. Spherical ZnO-NPs were synthesized at different calcination temperatures. Transmission electron microscopy (TEM) imaging showed the formation most of nanoparticles in the size range of below 50 nm. The powder X-ray diffraction (PXRD) analysis revealed wurtzite hexagonal ZnO with preferential orientation in (101) reflection plane. In vitro cytotoxicity studies on neuro2A cells showed a dose dependent toxicity with non-toxic effect of concentration below 2 µg/mL. The synthesized ZnO-NPs using gum tragacanth were found to be comparable to those obtained from conventional reduction methods using hazardous polymers or surfactants and this method can be an excellent alternative for the synthesis of ZnO-NPs using biomaterials.