Synthesis and Properties of Polymers with an Organosilicon–Acetylene Backbone

Acetylene- and diacetylene-containing organosilicon polymers continue to be of great interest in academia, government, and industry due to their high thermo-oxidative stability combined with excellent solubility and processability characteristics. Progress in this field over the past 30 years is reported herein. We present and discuss the synthesis, characterization, and structure–property relationships related to these materials. Furthermore, properties for specific applications of these polymers are briefly summarized, such as absorption and emission spectroscopy, composite mechanical analysis, four-probe conductivity measurements, and electroluminescence.     

Structural and Dynamical Insight into PPARγ Antagonism: In Silico Study of the Ligand-Receptor Interactions of Non-Covalent Antagonists

The structural and dynamical properties of the peroxisome proliferator-activated receptor γ (PPARγ) nuclear receptor have been broadly studied in its agonist state but little is known about the key features required for the receptor antagonistic activity. Here we report a series of molecular dynamics (MD) simulations in combination with free energy estimation of the recently discovered class of non-covalent PPARγ antagonists. Their binding modes and dynamical behavior are described in details. Two key interactions have been detected within the cavity between helices H3, H11 and the activation helix H12, as well as with H12. The strength of the ligand-amino acid residues interactions has been analyzed in relation to the specificity of the ligand dynamical and antagonistic features. According to our results, the PPARγ activation helix does not undergo dramatic conformational changes, as seen in other nuclear receptors, but rather perturbations that occur through a significant ligand-induced reshaping of the ligand-receptor and the receptor-coactivator binding pockets. The H12 residue Tyr473 and the charge clamp residue Glu471 play a central role for the receptor transformations. Our results also demonstrate that MD can be a helpful tool for the compound phenotype characterization (full agonists, partial agonists or antagonists) when insufficient experimental data are available.     

β-Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Pipemidic Acid: Characterization and Bioactivity Evaluation

The aptitude of cyclodextrins (CDs) to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA), a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and ¹H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC_50s and EC_90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.     

Evaluation of the Effect of Nanosilica on Thermal and Mechanical Properties of Metal–Metal and Metal–Glass Canola-Based Polyurethane/Nanosilica Adhesives

Nanocomposites with different concentration of nanofiller were prepared by adding nanosilica to the canola-based polyurethane matrix via in situ polymerization. The effect of nanosilica on the mechanical properties of adhesives was evaluated by tensile tests. Adhesive characteristics on metal–metal and metal–glass bondings were also evaluated by lap shear strength tests. Incorporation of nanosilica into the canola-based polyurethane enhanced both tensile and lap shear strength of synthesized adhesives. Also the effect of nanoparticles on glass transition temperature and thermal stability was investigated by differential scanning calorimetry and thermogravimetric analysis, respectively. The increase of nanosilica content in the polyurethane adhesives, thermal property of the nanocomposites improved.     

Decoding the Rich Biological Properties of Noble Gases: How Well Can We Predict Noble Gas Binding to Diverse Proteins?

The chemically inert noble gases display a surprisingly rich spectrum of useful biological properties. Relatively little is known about the molecular mechanisms behind these effects. It is clearly not feasible to conduct large numbers of pharmacological experiments on noble gases to identify activity. Computational studies of the binding of noble gases and proteins can address this paucity of information and provide insight into mechanisms of action. We used bespoke computational grid calculations to predict the positions of energy minima in the interactions of noble gases with diverse proteins. The method was validated by quantifying how well simulations could predict binding positions in 131 diverse protein X‐ray structures containing 399 Xe and Kr atoms. We found excellent agreement between calculated and experimental binding positions of noble gases. 94 % of all crystallographic xenon atoms were within 1 Xe van der Waals (vdW) diameter of a predicted binding site, and 97 % lay within 2 vdW diameters. 100 % of crystallographic krypton atoms were within 1 Kr vdW diameter of a predicted binding site. We showed the feasibility of large‐scale computational screening of all ≈60 000 unique structures in the Protein Data Bank. This will elucidate biochemical mechanisms by which these novel ‘atomic drugs’ elicit their valuable biochemical properties and identify new medical uses.     

Evaluation of the Interaction and Adsorption of γ-Glycidoxy propyl trimethoxy silane with Grit-Blasted Aluminium: A ToF-SIMS and XPS Study

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) have been employed to study the adsorption and interaction of γ-glycidoxy propyl trimethoxy silane (GPS) with grit-blasted aluminium.

GPS displaces adventitious hydrocarbon either by covalent bond formation between GPS and aluminium, or adsorption, when GPS is deposited on the aluminium. ToF-SIMS fragments present at a nominal mass m/z = 71 were peak-fitted to seven peaks by using CasaXPS Software. AlOSi⁺ and Si⁺ were used to establish a relationship between covalent bond formation and the adsorption process. It is found that the adsorption isotherms of Si⁺ relating to the adsorption of GPS were of the Langmuir type. The interfacial bonding between GPS and aluminium is mainly covalent at low solution concentrations. At higher concentrations (greater than 4.5 × 10^?4 M) all the sites for the covalent bond formation appear to be occupied while these for the acid-base interaction are still available and then become fully occupied at solution concentrations of 4.5 × 10^?2 M and above.     

Modulation of Pharmacologically Relevant Properties of Piperidine Derivatives by Functional Groups in an Equatorial or Axial β-Position to the Amino Group

Thirteen epimeric pairs of 5-substituted N-piperonyl-3-phenylpiperidine derivatives were synthesized in order to explore the stereospecific modulation of basicity, lipophilicity, aqueous solubility, and membrane permeation by functional groups in equatorial or axial positions beta to the amine unit. While this comprehensive data set provides enhanced insight into multiple factors that affect basicity and lipophilicity, it fills an important knowledge gap, providing a frame of reference for the property-based design of bioactive compounds. Impacts on amine basicity are very pronounced for the β-equatorial functional groups and parallel basicity-lowering effects known for acyclic amine derivatives. For β-axial functional groups, the basicity-lowering effects are generally decreased, with the nitrile group as the only exception. Basicity and lipophilicity modulations observed for β-axial functional groups are quite diverse and rationalized in terms of intramolecular hydrogen bonding, dipolar interactions, and special solvation effects. Aqueous solubility and (artificial) membrane permeability are discussed with reference to lipophilicity.     

Synthesis and Sulfonation of an Aluminum-Based Metal–Organic Framework with Microwave Method and Using for the Esterification of Oleic Acid

Journal of Inorganic and Organometallic Polymers and Materials - In this study, the synthesis of MIL-53(Al) (Material Institute Lavoisier, MIL) material, which is an aluminum-containing...     

Evaluation of the presence of bacteria in food and environment of an Oncological Service of a National Hospital, San José, Costa Rica

The microbiological quality of 92 samples from the Oncological Service of a National Hospital, San José, Costa Rica was evaluated during the months of February to July, 2002. Of these samples, 48 were from salads, refreshments, and fruits and 44 from surfaces, air and hands of the medical personnel. The presence of total and fecal coliforms was determined by the total plate count technique, using Violet Red Bile Agar for the isolation of total and fecal coliforms, Baird-Parker Agar for Staphylococcus aureus, Cetrimide Agar for Pseudomonas and Listeria was enriched in University of Vermont Broth, Fraizer Broth and isolated in Oxford Agar. From the food samples analyzed, 77% were positive for at least one of the parameters studied; the fruits presented the greater contamination (94%) and the cooked salads the minor, even though Listeria was isolated in 13% of them. All tested salads (100%) were positive for fecal coliforms. Pseudomonas and S. aureus were isolated from fruits, raw salads, and refreshments. All the analyzed surfaces, with an exception, were negative for the parameters evaluated. 75% of the hands of the medical personnel were positive for at least one of the parameters evaluated; 25% had total coliforms (2.8x10(3) UFC/hand), 13% fecal coliforms (2.4x10(3) UFC/ hand), 69% S. aureus (1.3x10(3) UFC/hand) and 19% Pseudomonas sp. 115 isolates were randomly selected, and identified using miniaturized tests (API). When comparing these identifications with the 166 isolations done at the Clinical Laboratory of the Hospital from the infected patients of oncology, by means of variance analysis, it was determined that both bacterial populations were statistically similar.     

Application of zirconium (IV) acetylacetonate to the copolymerization of glycolide with ɛ-caprolactone and lactide

Summary A study on the copolymerization of glycolide with lactide and glycolide with ɛ-caprolactone was performed in the presence of zirconium (IV) acetylacetonate at moderate temperatures (100° and 150°C). Zirconium acetylacetonate appeared to be an efficient initiator of copolymerization. The obtained polymers were characterized by high molecular weights. Considerable influence of transesterification on the polymer chain microstructure was found. Received: 13 October 1998/Revised version: 4 January 1999/Accepted: 4 January 1999     

“Click” Synthesis of a Heterobifunctional Ferrocenyl Dendrimer with Molecular Recognition Properties and Influence of the Ferrocenyl Redox Potential on the Formation of Gold Nanoparticles

Alkyne protection by complexation of ethynylferrocene with dicobalt octacarbonyl followed by regioselective acetylation, then deprotection and “click” reaction with a nona-azido-terminated arene-cored dendrimer leads to the heterodifunctional nona(1,2,3-triazolyl-acetylferrocenyl) dendrimer. Cyclic voltammetry of this metallodendrimer shows recognition of both ATP^2? and Pd²⁺. HAuCl₄ is reduced much more slowly to gold nanoparticles by the nona(triazolyl-acetylferrocenyl dendrimer than by the nona(triazolylferrocenyl) dendrimer due to the shift of redox potential in the new heterodifunctional dendrimer compared to that of the parent ferrocenyl dendrimer.     

Membrane Binding of Parkinson's Protein α-Synuclein: Effect of Phosphorylation at Positions 87 and 129 by the S to D Mutation Approach

Human α-synuclein, a protein relevant in the brain with so-far unknown function, plays an important role in Parkinson's disease. The phosphorylation state of αS was related to the disease, prompting interest in this process. The presumed physiological function and the disease action of αS involves membrane interaction. Here, we study the effect of phosphorylation at positions 87 and 129, mimicked by the mutations S87A, S129A (nonphosphorylated) and S87D, S129D (phosphorylated) on membrane binding. Local binding is detected by spin-label continuous-wave electron paramagnetic resonance. For S87A/D, six positions (27, 56, 63, 69, 76, and 90) are probed; and for S129A/D, three (27, 56, and 69). Binding to large unilamellar vesicles of 100 nm diameter of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine in a 1 : 1 composition is not affected by the phosphorylation state of S129. For phosphorylation at S87, local unbinding of αS from the membrane is observed. We speculate that modulating the local membrane affinity by phosphorylation could tune the way αS interacts with different membranes; for example, tuning its membrane fusion activity.     

Thiazolidinediones: An In–Depth Study of Their Synthesis and Application to Medicinal Chemistry in the Treatment of Diabetes Mellitus

2,4-Thiazolidinedione (TZD) is a privileged and highly utilised scaffold for the development of pharmaceutically active compounds. This sulfur-containing heterocycle is a versatile pharmacophore that confers a diverse range of pharmacological activities. TZD has been shown to exhibit biological action towards a vast range of targets interesting to medicinal chemists. In this review, we attempt to provide insight into both the historical conventional and the use of novel methodologies to synthesise the TZD core framework. Further to this, synthetic procedures utilised to substitute the TZD molecule at the activated methylene C₅ and N₃ position are reviewed. Finally, research into developing clinical agents, which act as modulators of peroxisome proliferator-activated receptors gamma (PPARγ), protein tyrosine phosphatase 1B (PTP1B) and aldose reductase 2 (ALR2), are discussed. These are the three most targeted receptors for the treatment of diabetes mellitus (DM).     

How Do Phenolic Acids Change the Secondary and Tertiary Structure of Gliadin? Studies with an Application of Spectroscopic Techniques

The effect of the chemical structure of selected phenolic acids on the molecular organization of gliadins was investigated with the application of Fourier Transform Infrared (FTIR) technique, steady-state, and time-resolved fluorescence spectroscopy. Hydroxybenzoic (4-hydroxybenzoic, protocatechuic, vanillic, and syringic) and hydroxycinnamic (coumaric, caffeic, ferulic, sinapic) acids have been used as gliadins modifiers. The results indicated that hydroxybenzoic acids due to their smaller size incorporate into spaces between two polypeptide chains and form a hydrogen bond with them leading to aggregation. Additionally, syringic acids could incorporate into hydrophobic pockets of protein. Whereas hydroxycinnamic acids, due to their higher stiffness and larger size, separated polypeptide chains leading to gliadin disaggregation. These acids did not incorporate into hydrophobic pockets.     

Combination of Aβ Secretion and Oxidative Stress in an Alzheimer-Like Cell Line Leads to the Over-Expression of the Nucleotide Excision Repair Proteins DDB2 and XPC

Repair of oxidative DNA damage, particularly Base Excision Repair (BER), impairment is often associated with Alzheimer’s disease pathology. Here, we aimed at investigating the complete Nucleotide Excision Repair (NER), a DNA repair pathway involved in the removal of bulky DNA adducts, status in an Alzheimer-like cell line. The level of DNA damage was quantified using mass spectrometry, NER gene expression was assessed by qPCR, and the NER protein activity was analysed through a modified version of the COMET assay. Interestingly, we found that in the presence of the Amyloid β peptide (Aβ), NER factors were upregulated at the mRNA level and that NER capacities were also specifically increased following oxidative stress. Surprisingly, NER capacities were not differentially improved following a typical NER-triggering of ultraviolet C (UVC) stress. Oxidative stress generates a differential and specific DNA damage response in the presence of Aβ. We hypothesized that the release of NER components such as DNA damage binding protein 2 (DDB2) and Xeroderma Pigmentosum complementation group C protein (XPC) following oxidative stress might putatively involve their apoptotic role rather than DNA repair function.     

Synthesis,structure and single-molecule magnet characterization of Dy2 dinuclear complexes with an 8–hydroxyquinoline carbohydrazone ligand

The employment of an 8-hydroxyquinoline carbohydrazone tetradentate ligand, 8-hydroxyquinoline-2-carboxaldehyde-(benzoyl)hydrazone (H₂L), DyCl₃·6H₂O and Et₃N has led to the formation of dinuclear Dy(III) complex [Dy₂(HL)₂Cl₄(CH₃OH)₂], (1) and [Dy₂(HL)₂((PhO)₂PO₂)₄]·2(CH₃OH) (2) in the presence of excess amount of bridging diphenyl phosphate anion, (PhO)₂PO^2 −. X-ray crystallography data revealed that two Dy^III atoms in 1 are doubly bridged by the two phenolato oxygen atoms of HL⁻ ligands, however, the Dy^III atoms are bridged by additional two deprotonated μ_1,3-phosphate anions in 2. Each of the two lanthanide ions is eight-coordinated and is located in the different symmetry with triangular dodecahedron (D_2d) for Dy^III in 1 and elongated triangular bipyramid (D_3h) for Dy^III in 2. Dc magnetic susceptibility studies in the 2–300 K range reveal the weak antiferromagnetic interaction for 1 and 2. Both of them showed field-induced slow magnetic relaxation behavior with the U_eff for 1 of 46.0 K higher than 36.8 K for 2.