Effects of external global harmonic influence on chimera states

Nonlinear Dynamics - The effects of the global harmonic force on an ensemble of nonlocally coupled chaotic Rössler oscillators is studied. The autonomous ensemble without external force...     

Conformational Dynamics Underlies Different Functions of Human KDM7 Histone Demethylases

The human KDM7 subfamily histone H3 Nϵ-methyl lysine demethylases PHF8 (KDM7B) and KIAA1718 (KDM7A) have different substrate selectivities and are linked to genetic diseases and cancer. We describe experimentally based computational studies revealing that flexibility of the region linking the PHD finger and JmjC domains in PHF8 and KIAA1718 regulates interdomain interactions, the nature of correlated motions, and ultimately H3 binding and demethylation site selectivity. F279S an X-linked mental retardation mutation in PHF8 is involved in correlated motions with the iron ligands and second sphere residues. The calculations reveal key roles of a flexible protein environment in productive formation of enzyme-substrate complexes and suggest targeting the flexible KDM7 linker region is of interest from a medicinal chemistry perspective.     

Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels

Compositions based on chitosan/β-glycerophosphate hydrogels with highly porous polylactide granules can be used to obtain moldable bone graft materials that have osteoinductive and osteoconductive properties. To eliminate the influence of such characteristics as chain length, degree of purification, and molecular weight on a designed material, the one-stock chitosan sample was reacetylated to degrees of deacetylation (DD%) of 19.5, 39, 49, 55, and 56. A study of the chitosan/β-glycerophosphate hydrogel with chitosan of a reduced DD% showed that a low degree of deacetylation increased the MSCs (multipotent stromal cells) viability rate in vitro and reduced the leukocyte infiltration in subcutaneous implantation to Wistar rats in vivo. The addition of 12 wt% polylactide granules resulted in optimal composite mechanical and moldable properties, and increased the modulus of elasticity of the hydrogel-based material by approximately 100 times. Excessive filling of the material with PLA (polylactide) granules (more than 20%) led to material destruction at a ~10% strain. Osteoinductive and osteoconductive properties of the chitosan hydrogel-based material with reacetylated chitosan (39 DD%) and highly porous polylactide granules impregnated with BMP-2 (bone morphogenetic protein-2) have been demonstrated in models of orthotopic and ectopic bone formation. When implanted into a critical-size calvarial defect in rats, the optimal concentration of BMP-2 was 10 μg/mL: bone tissue areas filled the entire material’s thickness. Implantation of the material with 50 μg/mL BMP-2 was accompanied with excessive growth of bone tissue and material displacement beyond the defect. Significant osteoinductive and osteoconductive properties of the material with 10 μg/mL of BMP-2 were also shown in subcutaneous implantation.     

Exploring the Interplay between Drug Release and Targeting of Lipid-Like Polymer Nanoparticles Loaded with Doxorubicin

Targeted delivery of doxorubicin still poses a challenge with regards to the quantities reaching the target site as well as the specificity of the uptake. In the present approach, two colloidal nanocarrier systems, NanoCore-6.4 and NanoCore-7.4, loaded with doxorubicin and characterized by different drug release behaviors were evaluated in vitro and in vivo. The nanoparticles utilize a specific surface design to modulate the lipid corona by attracting blood-borne apolipoproteins involved in the endogenous transport of chylomicrons across the blood–brain barrier. When applying this strategy, the fine balance between drug release and carrier accumulation is responsible for targeted delivery. Drug release experiments in an aqueous medium resulted in a difference in drug release of approximately 20%, while a 10% difference was found in human serum. This difference affected the partitioning of doxorubicin in human blood and was reflected by the outcome of the pharmacokinetic study in rats. For the fast-releasing formulation NanoCore-6.4, the AUC_0→1h was significantly lower (2999.1 ng × h/mL) than the one of NanoCore-7.4 (3589.5 ng × h/mL). A compartmental analysis using the physiologically-based nanocarrier biopharmaceutics model indicated a significant difference in the release behavior and targeting capability. A fraction of approximately 7.310–7.615% of NanoCore-7.4 was available for drug targeting, while for NanoCore-6.4 only 5.740–6.057% of the injected doxorubicin was accumulated. Although the targeting capabilities indicate bioequivalent behavior, they provide evidence for the quality-by-design approach followed in formulation development.     

Novel Highly Energetic Pyrazoles: N‐Trinitromethyl‐Substituted Nitropyrazoles

A new family of energetic compounds, nitropyrazoles bearing a trinitromethyl moiety at the nitrogen atom of the heterocycle, was designed. The desirable high‐energy dense oxidizers 3,4‐dinitro‐ and 3,5‐dinitro‐1‐(trinitromethyl)pyrazoles were synthesized in good yields by destructive nitration of the corresponding 1‐acetonylpyrazoles. All of the prepared compounds were fully characterized by multinuclear NMR and IR spectroscopy, as well as by elemental analysis. Single‐crystal X‐ray diffraction studies show remarkably high density. Impact sensitivity tests and thermal stability measurements were also performed. All of the pyrazoles possess positive calculated heats of formation and exhibit promising energetic performance that is the range of 1,3,5‐trinitroperhydro‐1,3,5‐triazine and pentaerythritol tetranitrate. The new pyrazoles exhibit positive oxygen balance and are promising candidates for new environmentally benign energetic materials.     

A structural study of (1RS,2SR,3RS,4SR,5RS)‐2,4‐dibenzoyl‐1,3,5‐triphenylcyclohexan‐1‐ol chloroform hemisolvate and (1RS,2SR,3RS,4SR,5RS)‐2,4‐dibenzoyl‐1‐phenyl‐3,5‐bis(2‐methoxyphenyl)cyclohexan‐1‐ol

(1RS,2SR,3RS,4SR,5RS)‐2,4‐Dibenzoyl‐1,3,5‐triphenylcyclohexan‐1‐ol or (4‐hydroxy‐2,4,6‐triphenylcyclohexane‐1,3‐diyl)bis(phenylmethanone), C₃₈H₃₂O₃, (1), is formed as a by‐product in the NaOH‐catalyzed synthesis of 1,3,5‐triphenylpentane‐1,5‐dione from acetophenone and benzaldehyde. Single crystals of the chloroform hemisolvate, C₃₈H₃₂O₃·0.5CHCl₃, were grown from chloroform. The structure has triclinic (P) symmetry. One diastereomer [as a pair of (1RS,2SR,3RS,4SR,5RS)‐enantiomers] of (1) has been found in the crystal structure and confirmed by NMR studies. The dichoromethane hemisolvate has been reported previously [Zhang et al. (2007). Acta Cryst. E 63 , o4652]. (1RS,2SR,3RS,4SR,5RS)‐2,4‐Dibenzoyl‐3,5‐bis(2‐methoxyphenyl)‐1‐phenylcyclohexan‐1‐ol or [4‐hydroxy‐2,6‐bis(2‐methoxyphenyl)‐4‐phenylcyclohexane‐1,3‐diyl]bis(phenylmethanone), C₄₀H₃₆O₅, (2), is also formed as a by‐product, under the same conditions, from acetophenone and 2‐methoxybenzaldehyde. Crystals of (2) have been grown from chloroform. The structure has orthorhombic (Pca2₁) symmetry. A diastereomer of (2) possesses the same configuration as (1). In both structures, the cyclohexane ring adopts a chair conformation with all bulky groups (benzoyl, phenyl and 2‐methoxyphenyl) in equatorial positions. The molecules of (1) and (2) both display one intramolecular O—H...O hydrogen bond.     

Correction to: The effect of small silver inclusions on the palladium activity in formicacid oxidation reaction and corrosion stability

A PdAg deposit containing ~ 25 at.% Ag is obtained by the electrochemical codeposition from an aqueous solution of Pd and Ag sulfates (Au support, 0.5 M H₂SO₄). The deposit is characterized by means of various physical, physicochemical, and electrochemical methods. The PdAg deposit demonstrates the ~ 2 times higher specific activity (per the electrochemically active surface area (EASA) of Pd) in the formic acid oxidation reaction (FAOR) as compared with the individual Pd deposit prepared under the same conditions. The effect of silver additions on the palladium activity depends on many factors. The corrosion stability of PdAg is studied in 0.5 M H₂SO₄ solution based on the overall cyclic voltammograms (CVAs) and also on anodic and cathodic half-cycles in the region E = 0.3 − 1.25 V (vs. reversible hydrogen electrode (RHE)). The electrochemical estimates are compared with the results of direct analytical determination of dissolution products in solution after anodic polarization of deposits. The total amounts of Pd dissolved substantially increase with incorporation of Ag, which is associated, first of all, with the considerable increase in the EASA; at the same time, the specific dissolution of Pd also substantially increases. The possible factors determining the active dissolution of PdAg deposits are discussed; in particular, the specific mechanism of their dissolution via silver adatoms is proposed.

     

Effect of non-covalent interactions in 2,5-di-Me-pyrazine-di-N-oxide - methanol – Carbon nanotube electrocatalytic system

Catalytic oxidation of methanol (MeOH) in the absence of noble metals and noble metal oxides as catalysts, and the use of metal-free materials are inexpensive and attractive process for practical use in electrocatalysis, sensors, and in direct methanol fuel cells. In previous works, it was found that the use of single-walled (SWCNT) or multi-walled (MWCNT) carbon nanotube paper electrodes instead of GC increases the catalytic efficiency of organic compounds oxidation in the presence of aromatic di-N-oxides by several times. In this work, the effect of non-covalent interactions on the catalytic efficiency of MeOH oxidation in the presence of 2,5-di-Me-pyrazine-di-N-oxide (Pyr₁) in 0.1 M Bu₄NClO₄ solution in acetonitrile at SWCNT and MWСNT paper electrodes was studied by the methods of quantum chemical modeling, Raman spectroscopy, and using electrochemical data. New factors determined the features of mechanism of MeOH oxidation on CNT electrodes and lead to an increase in the catalytic efficiency of the electrode process in comparison with the GC electrode were established.