On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

Nucleic acid sequences able to adopt a G-quadruplex conformation are overrepresented within the human genome. This evidence strongly suggests that these genomic regions have been evolutionary selected to play a pivotal role in several aspects of cell biology. In the present review article, we provide an overview on the biological impact of targeting G-quadruplexes in cancer. A variety of small molecules showing good G-quadruplex stabilizing properties has been reported to exert an antitumor activity in several preclinical models of human cancers. Moreover, promiscuous binders and multiple targeting G-quadruplex ligands, cancer cell defense responses and synthetic lethal interactions of G-quadruplex targeting have been also highlighted. Overall, evidence gathered thus far indicates that targeting G-quadruplex may represent an innovative and fascinating therapeutic approach for cancer. The continued methodological improvements, the development of specific tools and a careful consideration of the experimental settings in living systems will be useful to deepen our knowledge of G-quadruplex biology in cancer, to better define their role as therapeutic targets and to help design and develop novel and reliable G-quadruplex-based anticancer strategies.     

Ligands for selective metal ion extraction: A molecular modeling approach

We present a density functional theory (DFT) based study on interaction of alkali metal cations (Li⁺ and Na⁺) with macrocyclic crown ethers of different ring sizes. The minimum energy structures, binding energies, and binding enthalpies of crown ether–cation complexes have been determined with a correlated hybrid density functional, namely Becke’s three-parameter functional, B3LYP using a split valence basis function, 6-311++G(d, p). Geometry optimizations for all the crown ether–cation complexes were carried out with several initial guess structures based on semi-empirical PM3 optimized results. For both metal ions, the calculated values of binding energy and binding enthalpy increase with the increase in size of the crown ether ring, i.e. with the increase in the number of donor oxygen atoms in crown ether. The calculated values of gas phase binding energy for lithium ions are always higher than those for sodium ions in the case of all macrocyclic crown ethers studied at present. The calculated values of binding enthalpy are in good agreement with the reported experimental data.     

The building block approach to unusual alpha-amino acid derivatives and peptides

The building block approach was identified as a useful alternative to the commonly used Bücherer-Berg method for the preparation of cyclic unusual alpha-amino acid derivatives. The symmetrical building blocks were prepared by dialkylation of ethyl isocyanoacetate under solid-liquid phase transfer catalysis conditions while the unsymmetrical building blocks were prepared by a stepwise alkylation of the O'Donnell Schiff base. Metathesis reactions, Suzuki couplings, and cycloaddition reactions were utilized to assemble the building blocks.     

Asymmetric Intermolecular Mizoroki-Heck Reaction: From Phosphine/Phosphinite-Nitrogen to Phosphite-Nitrogen Ligands

This review discusses the latest developments in ligand design for the Pd-catalyzed asymmetric intermolecular Mizoroki-Heck reaction, from the successful phosphine/phosphinite-nitrogen ligands to the recently reported phosphite-nitrogen ligands. The presence of a biaryl phosphite group offers several advantages as a ligand scaffold for this process.     

An integrated approach to construct tantalum derivatives for electrocatalysis beyond the triiodide reduction reaction

The counter electrode (CE) is an essential component in dye-sensitized solar cells (DSSCs) to transfer electrons and catalyze triiodide reduction. In this research, efficient and cost-effective tantalum derivatives (oxide, nitride, carbide, oxynitride, and corresponding hybrids) are synthesized and utilized as CEs in DSSCs toward the triiodide reduction. The DSSC with mixed-anionic TaON CE achieves a cell efficiency of 5.46%, surpassing that with pristine TaO_x CE (5.20%) before nitriding treatment. Benefiting from the synergistic interaction between mesoporous carbon (MC) and TaC_0.95, TaC_0.95/MC hybrid CE-based DSSC possess superior cell efficiency of 7.23%, higher than that of respective TaC (6.24%) and MC (6.52%), especially standard Pt (6.34%). Furthermore, TaON and TaC_0.95/MC CEs exhibit durably great catalytic activity for I₃^- reduction. This work raises an effective and generally accepted approach to construct transition metal derivatives, which could utilize as low-priced Pt-free electrocatalysts for new energy devices.     

An approach to imprint irganox 1076: Potential application to the specific migration test in olive oil

Irganox 1076 is a hindered phenolic antioxidant commonly added to polyolefins, whose migration from the plastic packaging into the food is regulated by European legislation. The work herein reports on an initial approach to obtain a molecularly imprinted polymer (MIP) for Irganox 1076, a previously nonimprinted target. In a subsequent step, the application of the molecularly imprinted solid‐phase extraction (MISPE) to the fatty simulant olive oil is tested to get its determination free of interferences using high‐performance liquid chromatography with PDA detector. The influence of five variables, namely porogen, functional monomer, crosslinker, initiator, and initiation method was investigated through the synthesis of miniMIPs. The best results were obtained using methacrylic acid and ethylene glycol dimethacrylate in tetrahydrofuran under UV radiation with 2,2′‐azobis‐(2‐methylpropionitrile). The application of MISPE to olive oil showed the potential of the imprinted polymer to clean up complex matrices. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

The Outer-Coordination Sphere: Incorporating Amino Acids and Peptides as Ligands for Homogeneous Catalysts to Mimic Enzyme Function

Great progress has been achieved in the field of homogeneous transition metal-based catalysis; however, as a general rule these solution-based catalysts are still easily outperformed by their analogous enzyme counterparts, in terms of both rates and selectivity. This includes structural mimics of enzymatic active sites. This observation suggests that the features of the enzyme beyond the active site, i.e., the outer-coordination sphere, are important for enzymes' exceptional function. Directly mimicking the outer-coordination sphere requires the incorporation of amino acids and peptides as ligands for homogeneous catalysts. This effort has been attempted for many homogeneous catalysts which span the manifold of catalytic reactions including hydrogenation, hydroformylation, hydrogen production, oxygen activation, dioxygen transport, electron transfer, disproportionation of the superoxide anion radical, acylation, phosphorylation, esterification, ester hydrolysis, and hydrogen peroxide disproportionation. How much of the outer-coordination sphere to include in molecular catalysts and the preferential structural conformation of the appended section are long-standing questions. Synthetically incorporating an amino acid- or peptide-based outer-coordination sphere requires care to avoid unwanted side reactions with the large number of functional groups. Catalysis with amino acid or peptide containing catalysts requires careful consideration of solvent and pH to promote solubility, stabilize structure, optimize catalysis, and avoid catalyst degradation. This article reviews the current capability of synthesizing and characterizing this often challenging but very promising category of metal-based catalysts.     

Nitriles in heterocyclic synthesis: A new approach for the Synthesis of Thiazole derivatives

The reaction of 4-bromo-3-oxo-butyranilide ( 1 ) with KSCN afforded the thiocyanato derivative 2 . 2-Dicyanomethylthiazol-4-yl-acetanilide ( 3 ) was synthesised by reaction of 2 with malononitrile. A variety of substituted thiazol-2-yl malononitriles were prepared by reaction of 3 with hydroxylamine hydrochloride, phenylhydrazine and cinnamonitrile derivatives. The structure assignments of the new compounds are based mainly on ¹³C and ¹H-n.m.r. spectroscopic data.     

Ionic liquid batteries: Chemistry to replace alkaline/acid energy storage devices

Rather than depend on highly acidic or basic electrolytes, ionic liquids are used to create new types of solid state cells which mimic standard alkaline cells, but without the need for caustic electrolytes. Presented here is a non-aqueous approach to primary and secondary power sources, where the pure ionic liquid not only acts as the electrolyte/separator in both liquid and solid state batteries, but as a reactive species in the cell's electrochemical makeup. In this work, batteries are designed using standard cathode and anode materials such as MnO₂/Carbon, PbO₂, NiO, AgO and Zn. However, by using a solid polymer electrolyte composed of an ionic liquid and polyvinyl alcohol, novel types of solid state batteries are demonstrated with discharge voltages ranging up to 1.8 V, dependent upon the type of cathode and anode used. These batteries are characterized by ionic conductivity, initial voltage measurements, and discharge profiles.     

Polymerization of ethylene oxide initiated by lithium derivatives via the monomer-activated approach: Application to the direct synthesis of PS-b-PEO and PI-b-PEO diblock copolymers

The anionic polymerization of ethylene oxide (EO) initiated by lithium derivatives is extremely sluggish and only yields very low molar mass EO oligomers because of the low reactivity of lithium alkoxide species. We show here that using the monomer-activated anionic polymerization approach, one can activate the C-O-Li bonds towards EO polymerization at low temperature and in non polar media. Starting from living polystyryllithium and polyisoprenyllithium, addition of triisobutylaluminum (i-Bu₃Al) in excess to lithium species triggers the propagation reaction of EO, allowing the direct synthesis, in a few hours, of poly(styrene-b-ethylene oxide) and poly(isoprene-b-ethylene oxide) diblock copolymers, with a molar mass of the PEO block up to 10 000 g/mol.     

The Relation of Collector Redox Potential to Flotation Efficiency: Monothiocarbonates

Abstract

The redox potentials of monothiocarbonates and xanthates have been determined and a correlation established with their collector properties for the flotation of galena. Flotation efficiency increases with the ease of oxidation of the collector. The role in flotation of the oxidation products, the disulfides, is discussed.     

Heterocyclic synthesis with nitriles: A new approach to Thiophene and Thieno-[2,3-d]-pyrimidine derivatives

α-Cyano-β-thiocyanatomethyl cinnamonitrile ( 1 ) was transformed into 5-acetyl-2-amino-4-phenylthiophen-3-carbonitrile ( 3 ) on refluxing in acetic/sulphuric acid mixture. Compound 3 reacted with trichloroacetonitrile, formamide, carbon disulphide and ethylorthoformate.     

Fragmenting the S100B–p53 Interaction: Combined Virtual/Biophysical Screening Approaches to Identify Ligands

S100B contributes to cell proliferation by binding the C terminus of p53 and inhibiting its tumor suppressor function. The use of multiple computational approaches to screen fragment libraries targeting the human S100B–p53 interaction site is reported. This in silico screening led to the identification of 280 novel prospective ligands. NMR spectroscopic experiments revealed specific binding at the p53 interaction site for a set of these compounds and confirmed their potential for further rational optimization. The X‐ray crystal structure determined for one of the binders revealed key intermolecular interactions, thus paving the way for structure‐based ligand optimization.     

Tailored Media for Homogeneous Cellulose Chemistry: Ionic Liquid/Co‐Solvent Mixtures

Co‐solvents can minimize two of the major problems associated with the use of ionic liquids (ILs) as solvents for homogeneous derivatization of cellulose: high viscosity and limited miscibility with non‐polar reagents or reaction products. Thus, the effects of 18 solvents and 3 binary solvent mixtures on cellulose solutions in three ILs were systematically studied with respect to the solution phase behavior. The applicable limits of these mixtures were evaluated and general guidelines for the use of co‐solvents in cellulose chemistry could be advanced: Appropriate co‐solvents should have $E_{{\rm T}}^{{\rm N}} $ values (normalized empirical polarity) > 0.3, very low “acidity” (α < 0.5), and relatively high “basicity” (β ≥ 0.4). Moreover, novel promising co‐solvents and binary co‐solvent mixtures were identified.