Exploring the Molecular Interactions of 7,8-Dihydroxyflavone and Its Derivatives with TrkB and VEGFR2 Proteins

7,8-Dihydroxyflavone (7,8-DHF) is a TrkB receptor agonist, and treatment with this flavonoid derivative brings about an enhanced TrkB phosphorylation and promotes downstream cellular signalling. Flavonoids are also known to exert an inhibitory effect on the vascular endothelial growth factor receptor (VEGFR) family of tyrosine kinase receptors. VEGFR2 is one of the important receptors involved in the regulation of vasculogenesis and angiogenesis and has also been implicated to exhibit various neuroprotective roles. Its upregulation and uncontrolled activity is associated with a range of pathological conditions such as age-related macular degeneration and various proliferative disorders. In this study, we investigated molecular interactions of 7,8-DHF and its derivatives with both the TrkB receptor as well as VEGFR2. Using a combination of molecular docking and computational mapping tools involving molecular dynamics approaches we have elucidated additional residues and binding energies involved in 7,8-DHF interactions with the TrkB Ig2 domain and VEGFR2. Our investigations have revealed for the first time that 7,8-DHF has dual biochemical action and its treatment may have divergent effects on the TrkB via its extracellular Ig2 domain and on the VEGFR2 receptor through the intracellular kinase domain. Contrary to its agonistic effects on the TrkB receptor, 7,8-DHF was found to downregulate VEGFR2 phosphorylation both in 661W photoreceptor cells and in retinal tissue.     

The Influence of a Phase Transition in Poly(oxyethylene)/Poly(oxypropylene)/Poly(oxyethylene) Block Copolymer Surfactants on the Properties of Material Adsorbed from Dilute Aqueous Solution

In this study the adsorption of poloxamer block copolymer surfactants to polystyrene latex has been studied at a range of temperatures. It has been noted previously that the adsorption first falls, then rises and falls again as the temperature is increased, due to the existence of a phase transition in aqueous solutions of these surfactants at specific temperatures, which may be a critical micelle temperature. The present study shows that the hydrophobicity of the surface changes in a manner related to the amount of poloxamer adsorbed (i.e. is greatly influenced by the temperature of adsorption in relation to the transition temperature). The coating layer thickness, however, is essentially unchanged by the temperature of adsorption (i.e. not related to the amount adsorbed), but is influenced by the temperature at which the sizing was undertaken. This is due to dehydration of the poly (oxyethylene) with increasing temperature. The data presented here provide a possible explanation for the changes in biological distribution of poloxamer coated particles which occur when they are injected into animals.     

Aging-Induced Metal Redistribution in Bimetallic Catalysts

Alloy particles were detected by XRD in bimetallic catalysts, made from physical mixtures of powders comprising distinct metal-support combinations (e.g., Pd on alumina and Rh on ceria-zirconia), following high-temperature redox aging. The morphology of the catalysts was examined by TEM, and the compositional structure of some of the alloy particles was determined. Two different effects of the redistribution of metals on oxygen-storage capacity were identified, one due to Pd enrichment of the surface of Pd-Rh alloy particles and the other due to loss of contact between metal and ceria-zirconia.     

Revised Model of Strain in Ceria–Zirconia-Encapsulated Precious-Metal Particles

A previously proposed model of strain in ceria–zirconia-encapsulated precious-metal particles is revised to reflect several new observations: encapsulation of unstrained Pt particles, quantitative relation between partial reduction and the change in ceria–zirconia cell parameters, temperature/time dependence of strain relaxation/imposition in encapsulated Pd and Rh particles, and strained PdO. According to the revised model, the main cause of strain is partial oxidation of the precious metal (rather than the change in oxygen content of ceria–zirconia, as originally suggested).     

Water as a Promoter of the Complete Oxidation of Volatile Organic Compounds over Uranium Oxide Catalysts

The effect of water addition on the complete oxidation of benzene and propane VOCs by uranium oxide catalysts has been investigated. Benzene oxidation was studied using a silica supported U₃O₈ catalyst. Complete oxidation is promoted by the addition of 2.6% water compared with the reactivity when no water is added to the reactant feed. Increasing the water concentration to 12.1% resulted in a suppression of oxidation activity. Investigation of propane oxidation using U₃O₈ shows a dramatic promotion of activity. Propane conversion was ca. 50% at 600 °C without added water, whilst it increased to 100% at 400 °C with the addition of 2.6% water. A comparison of oxidation activity has been made with Mn₂O₃, an oxide recognised for complete oxidation. In contrast to the U₃O₈ catalysts the addition of 2.6% water suppresses the activity of Mn₂O₃. In situ powder X-ray diffraction studies showed that the bulk U₃O₈ structure was stable under all the reaction conditions. The origin of the increased activity is not clear but may be due to modification of the catalyst surface and the contribution from new reaction pathways such as steam reforming.     

Premodification of Pt/γAl2O3 with Cinchonidine for the Enantioselective Hydrogenation of Ethyl Pyruvate: Effect of Premodification Conditions on Reaction Rate and Enantioselection

The premodification of a 5 wt% Pt/-Al₂O₃ catalyst with cinchonidine (0.01 and 0.2 g g^-1 _catalyst) is described and discussed. Premodification is carried out by treating the catalyst with a solution of cinchonidine followed by solvent removal. Catalysts premodified in this way give the same ee and initial rate of reaction for the enantioselective hydrogenation of ethyl pyruvate as those using the standard in situ modification procedure. Investigations of different solvents for premodification and reaction (dichloromethane, ethanol) show that it is the solvent used for the reaction that controls the observed enantioselection. Premodified catalysts also display the initial transient behavior typically observed with in situ modified catalysts in which the ee increases with conversion in the early part of the reaction. Premodified catalysts show an enhanced rate of reaction when ethanol is used as the reaction solvent compared with in situ modified catalysts under the same conditions. Premodification using aerobic conditions gives the best results and premodified catalysts can be stored prior to use for up to a week without loss of catalytic performance.     

Oxidation of Glycerol Using Supported Gold Catalysts

A series of supported gold catalysts (0.25, 0.5, 1.0 wt% Au/graphite) have been investigated for the oxidation of glycerol and propan-1,2-diol. The 1 wt% Au/graphite catalyst is found to give 100% selectivity to the mono acid product, isolated as the sodium salt, as long as NaOH is present. The catalysts are characterized by TEM and cyclic voltammetry. By TEM, active catalysts all comprise fairly broad-size distributions (5–50 nm diameter) for the gold nanoparticles, although most are ca. 25 nm in diameter. An inactive 1 wt% Au/graphite is shown to have considerably larger particle sizes (>50 nm) and this indicates that there may be an optimum particle size for the desired catalysis. Characterization using cyclic voltammetry of active Au/graphite catalysts carried out in NaOH reveals the presence of an oxide species that may be responsible for the observed catalysis. In contrast, the inactive 1 wt% Au/graphite catalyst shows no oxidation in the cyclic voltammetry experiments.     

A mathematical model for dilating, non-cohesive granular flows in steep-walled hoppers

A new variable-density plastic flow model is developed, in which the Drucker Prager yield condition holds identically, but the corresponding flow condition contains the time derivative of density (or the divergence of mass flux), in order to satisfy mass conservation. This “softening” model is applied to the steady radial flow of a cohesionless granular material from steep-walled wedge and conical hopper. Density is assumed to vary with pressure. The variation of density within the hopper is shown to decrease the mass discharge rate, relative to the incompressible model, by a similar amount to the fractional reduction in voidage about the orifice. The predicted mass discharge decreased with increasing internal friction angle. This paper assumed that the inclination of the stagnant region in hopper flow is described by regression curves fitted to data from Brown and Richards. Approximate agreement between the theory of this paper and voidage measurements by Fickie et al. was obtained. Approximate agreement was also obtained with the published mass discharge rates of Nedderman and Beverloo for wedge and conical hoppers, respectively, and our results were insensitive to variations in internal angles of friction between about 25° and 35°. The steady equations considered here can only be satisfied approximately, supporting observations that granular flows are intrinsically transient.