Modeling and biological investigations of an unusual behavior of novel synthesized acridine-based polyamine ligands in the binding of double helix and G-quadruplex DNA

Three novel 2,7-substituted acridine derivatives were designed and synthesized to investigate the effect of this functionalization on their interaction with double-stranded and G-quadruplex DNA. Detailed investigations of their ability to bind both forms of DNA were carried out by using spectrophotometric, electrophoretic, and computational approaches. The ligands in this study are characterized by an open-chain (L1) or a macrocyclic (L2, L3) framework. The aliphatic amine groups in the macrocycles are joined by ethylene (L2) or propylene chains (L3). L1 behaved similarly to the lead compound m-AMSA, efficiently intercalating into dsDNA, but stabilizing G-quadruplex structures poorly, probably due to the modest stabilization effect exerted by its protonated polyamine chains. L2 and L3, containing small polyamine macrocyclic frameworks, are known to adopt a rather bent and rigid conformation; thus they are generally expected to be sterically impeded from recognizing dsDNA according to an intercalative binding mode. This was confirmed to be true for L3. Nevertheless, we show that L2 can give rise to efficient π-π and H-bonding interactions with dsDNA. Additionally, stacking interactions allowed L2 to stabilize the G-quadruplex structure: using the human telomeric sequence, we observed the preferential induction of tetrameric G-quadruplex forms. Thus, the presence of short ethylene spacers seems to be essential for obtaining a correct match between the binding sites of L2 and the nucleobases on both DNA forms investigated. Furthermore, current modeling methodologies, including docking and MD simulations and free energy calculations, provide structural evidence of an interaction mode for L2 that is different from that of L3; this could explain the unusual stabilizing ability of the ligands (L2>L3>L1) toward G-quadruplex that was observed in this study.     

The comprehensive in vitro evaluation of eight different calcium phosphates: Significant parameters for cell behavior

Eight different calcium phosphate nanoparticles, namely bovine bone bioapatite calcined at 500, 600, and 700°C, Mg-doped brushite, fluorinated calcium phosphate, Ca-deficient hydroxyapatite, hydroxyapatite, and tricalcium phosphate, were characterized employing physico-chemical methods. Their cytocompatibility was evaluated under human osteoblast-like cell line MG-63 culture conditions in elution media and via the direct interaction of cells with calcium phosphate nanoparticles. The main objective was to determine the correlation of the cell indices with the differently determined physical and chemical parameters of the calcium phosphates. Chemical composition, which contributes toward pH changes, and the calcium ion concentration in the medium appear to make up particularly significant factors; moreover, it was proved that the number of material types represents a further important aspect. In the case of a large number of material types, almost no correlation was determined between the analyzed parameters; however, in the case of a small number of apatite types, several positive correlations were found. It can be concluded that it is not possible to identify any monitored parameters that had a major impact on cell behavior or, at least, such an effect which can be generalized. It appears more likely that cell behavior is affected by the interplay of various parameters.     

Quantitative Assessment of Affinity Selection Performance by Using DNA-Encoded Chemical Libraries

DNA-encoded chemical libraries are often used for the discovery of ligands against protein targets of interest. These large collections of DNA-barcoded chemical compounds are typically screened by using affinity capture methodologies followed by PCR amplification and DNA sequencing procedures. However, the performance of individual steps in the selection procedures has been scarcely investigated, so far. Herein, the quantitative analysis of selection experiments, by using three ligands with different affinity to carbonic anhydrase IX as model compounds, is described. In the first set of experiments, quantitative PCR (qPCR) procedures are used to evaluate the recovery and selectivity for affinity capture procedures performed on different solid-phase supports, which are commonly used for library screening. In the second step, both qPCR and analysis of DNA sequencing results are used to assess the recovery and selectivity of individual carbonic anhydrase IX ligands in a library, containing 360 000 compounds. Collectively, this study reveals that selection procedures can be efficient for ligands with sub-micromolar dissociation constants to the target protein of interest, but also that selection performance dramatically drops if 10⁴ copies per library member are used as the input.     

Nano-to-macroporous TiO2 (anatase) by cold sintering process

Cold Sintering Process (CSP) was applied on commercial nanopowders to produce nanostructured TiO₂ anatase with nano-to-macro porosity. Nanoporous TiO₂ based materials were obtained by applying CSP at 150 °C and pressures up to 500 MPa on three TiO₂ nanopowders with different specific surface area (s.s.a. = 50, 90 and 370 m²/g), using water as transient aqueous environment. Although TiO₂ is insoluble in water, a density of 68% and s.s.a. = 117 m²/g were achieved from the powder with the highest specific surface area. A post annealing process at 500 °C increased the density up to 73% with a s.s.a. = 59 m²/g, and the crystallites dimensions passed from 110 Å in the powder to 130 Å in CSP material and 172 Å after post annealing. Finally, macroporosity was produced by using thermoplastic polymer beads as sacrificial templates within TiO₂ nanopowder during CSP, followed by a debonding at 500 °C.     

Sinanodonta woodiana (mollusca: bivalvia: unionidae): isolation and characterization of the first microsatellite markers

Sinanodonta woodiana (Lea, 1834) is a large Unionid species with a real invasion success. It colonized Europe, Central America, the Indonesian Islands and recently North America. The species life cycle involves a larval parasitic stage on freshwater fish species which contributes to the spread of the mussel. In this paper we describe, for the first time, eight polymorphic microsatellite loci for the species Sinanodonta woodiana. The genetic screening of individuals confirmed that all loci were highly polymorphic. The number of alleles per locus ranged from 7 to 14 and the observed heterozygosity ranged from 0.650 to 0.950. These loci should prove useful to study the species population genetics which could help to infer important aspects of the invasion process.     

Unified study of flow regimes and gas holdup in the presence of positive and negative surfactants in a non-uniformly aerated bubble column

In this paper, a study on the global gas holdup and hydrodynamic flow regimes developed in a partially aerated bubble column at variable air superficial velocities (U_G) in the presence of positive and negative surfactants is presented. According to the results obtained, despite the different liquid phase properties variation caused by the presence of positive (alcohols) and negative (electrolytes) surfactants, both reduce coalescence and the effect in the gas holdup (ε_G) is equivalent: it increases with the surfactant concentration (C) but only when the (C/C_t) ratio is clearly above 1, being C_t the transition concentration. Contrary to the results obtained for totally aerated bubble columns, for lower values of the (C/C_t) ratio, the holdup remains practically invariable. Considering the crucial role that C and C_t play in the resulting ε_G, a new prediction equation for ε_G accounting for the ratio (C/C_t) and U_G is presented and its performance for both types of surfactants validated. Additionally, visual and wall pressure fluctuations studies reveal that the vortical flow (VF), characterized by an oscillating bubble plume, prevails in ultrapure water (UPW) but results destabilized in the presence of surfactants. This destabilization results in an evolution to a pseudo-steady flow regime, the double cell turbulent flow regime (DCTF), characterized by a quasi-static bubble jet, located at the column centerline that determines the appearance of two static symmetrical vortices     

Reviewing Rare Earth Succinate Frameworks from the Reticular Chemistry Point of View: Structures,Nets, Catalytic and Photoluminescence Applications

The intense development that Metal-Organic Frameworks have experienced along the last two decades, reflects the interest on these compounds as a new generation of multifunctional materials with diverse applications. The first works of Prof. Omar Yaghi devoted to obtain open frameworks by combining rigid aromatic linkers and a variety of metal centers, encouraged the creativity of the scientific community to designcoordination polymers employing aliphatic ligands as multitopic building blocks . Here, a revision of the literature dedicated to rare earth coordination networks mainly based in succinate ligand and derivatives is performed. A structural analysis of 2D and 3D frameworks based on rare earth elements and succinate, was carried out considering their inner connectivities and topologies with focus on those compounds with potential photoluminescent and catalytic technological applications. Thus, a variety of optical behaviours regarding the emission mechanisms, colours, lifetimes, quantum yields as well as chemical/thermal sensing properties are presented and compared with related phases found in literature. The catalytic performance of several rare earth-succinates in three important reactions is discussed in terms of their acidity, dimensionality and available active centers towards the formation of the desired products analysing parameters such as selectivity, yields and TOFs.     

Nonisothermal crystallization behavior of a biodegradable segmented copolymer constituted by glycolide and trimethylene carbonate units

Nonisothermal crystallization of a segmented copolymer constituted by glycolide and trimethylene carbonate units was studied from both the melt and the glass state by optical microscopy, differential scanning calorimetry and time‐resolved X‐ray diffraction techniques. Positive spherulites with a fibrilar appearance were always obtained and corresponded to the crystallization of the polyglycolide hard segments. A single crystallization regime and the kinetic parameters were inferred from optical microscopy data on crystallizations performed at different cooling/heating rates. The parameters were in good agreement with values previously deduced from isothermal experiments. Isoconversional data of melt and glass nonisothermal crystallizations were combined to obtain the Lauritzen and Hoffman parameters from calorimetric data. Results revealed again the existence of a single crystallization regime with a secondary nucleation constant close to that deduced from isothermal DSC experiments. Morphological changes occurring during the hot and cold crystallization were evaluated by time‐resolved SAXS/WAXD experiments employing synchrotron radiation. Measurements showed that significant differences on the lamellar thicknesses exist depending on the crystallization process. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Phosphorus‐containing poly(ester‐imide)–polydimethylsiloxane copolymers

New phosphorus‐containing poly(ester‐imide)‐polydimethylsiloxane copolymers were prepared by solution polycondensation of 1,4‐[2‐(6‐oxido‐6H‐dibenz < c,e > < 1, 2 > oxaphosphorin‐6‐yl)]naphthalene‐bis(trimellitate) dianhydride with a mixture of an aromatic diamine (1,3‐bis(4‐aminophenoxy)benzene) and α,ω‐bis(3‐aminopropyl)oligodimethylsiloxane of controlled molecular weight, in various ratios. Poly(amic acid) intermediates were converted quantitatively to the corresponding polyimide structures using a solution imidization procedure. The polymers are easily soluble in polar organic solvents, such as N‐methyl‐2‐pyrrolidone and N,N‐dimethylformamide, as well as in less polar solvents such as tetrahydrofuran. They show good thermal stability, the decomposition temperature being above 370 °C. The glass transition temperatures are in the range 165–216 °C. Solutions of the polymers in N‐methyl‐2‐pyrrolidone exhibit photoluminescence in the blue region. Copyright © 2010 Society of Chemical Industry     

Flow Instabilities in Linear and Branched Syndiotactic Poly(propylene)s

Extrusion flow experiments of linear and branched syndiotactic poly(propylene)s were carried out. The work was focused on flow instabilities. Ionized radiation was employed to induce long chain branching in linear samples. Sharkskin and melt fracture were postponed in the case of slightly long branched samples, which possess an enhanced melt elasticity compared to linear samples. For the most elastic samples the nature of the flow instability changed: sharkskin disappeared and melt fracture was observed instead. The correlation between sharkskin and melt strength results is discussed.