Synthesis and in Vitro Characterisation of Ifenprodil‐Based Fluorescein Conjugates as GluN1/GluN2B N‐Methyl‐D‐aspartate Receptor Antagonists

GluN2B‐containing NMDA receptors are involved in many important physiological functions and play a pivotal role in mediating pain as well as in several neurodegenerative disorders. We aimed to develop fluorescent probes to target the GluN2B subunit selectively in order to allow better understanding of the relationships between receptor localisation and physiological importance. Ifenprodil, known as the GluNR2B antagonist of reference, was chosen as the template for the elaboration of probes. We had previously reported a fluorescein conjugate that was shown (by confocal microscopy imaging of DS‐red‐labelled cortical neurons) to bind specifically to GluN2B. To elaborate this probe, we explored the influence of both the nature and the attachment point of the spacer between the fluorophore and the parent compound, ifenprodil. We performed chemical modifications of ifenprodil at the benzylic position and on the phenol ring by introducing secondary amine or amide functions and evaluated alkyl chains from two to 20 bonds either including or not including secondary amide functions as spacers. The previously developed probe was found to display the greatest activity in the inhibition of NMDA‐induced Ca²⁺ influx by calcium imaging experiments on HEK293 cells transfected with the cDNA encoding for GluN1‐1A and GluN2B. Further investigations revealed that this probe had a neuroprotective effect equivalent to that of ifenprodil in a standard test for neurotoxicity. Despite effects of lesser amplitude with these probes relative to ifenprodil, we demonstrated that they displaced [³H]ifenprodil in mouse brain slices in a similar manner.     

High‐Temperature Creep Behavior of Dense SiOC‐Based Ceramic Nanocomposites: Microstructural and Phase Composition Effects

In this work, dense monolithic polymer‐derived ceramic nanocomposites (SiOC, SiZrOC, and SiHfOC) were synthesized via hot‐pressing techniques and were evaluated with respect to their compression creep behavior at temperatures beyond 1000°C. The creep rates, stress exponents as well as activation energies were determined. The high‐temperature creep in all materials has been shown to rely on viscous flow. In the quaternary materials (i.e., SiZrOC and SiHfOC), higher creep rates and activation energies were determined as compared to those of monolithic SiOC. The increase in the creep rates upon modification of SiOC with Zr/Hf relies on the significant decrease in the volume fraction of segregated carbon; whereas the increase of the activation energies corresponds to an increase of the size of the silica nanodomains upon Zr/Hf modification. Within this context, a model is proposed, which correlates the phase composition as well as network architecture of the investigated samples with their creep behavior and agrees well with the experimentally determined data.     

Synthesis and Pharmacological Evaluation of a series of the Agomelatine Analogues as Melatonin MT1/MT2 Agonist and 5‐HT2C Antagonist

Agomelatine is a naphthalenic analogue of melatonin that is in clinical use for the treatment of major depressive disorders. Interestingly, while agomelatine exhibits potent affinity for melatonin receptors, it binds with only moderate affinity to the serotonin 5‐HT_2C receptor. Optimization of agomelatine toward this target could further potentiate its clinical efficacy. To explore this hypothesis and to access derivatives in which a key point of agomelatine metabolism is blocked, a series of naphthalenic derivatives was designed and synthesized as novel analogues of agomelatine. Most of the prepared compounds exhibited good binding affinity at the melatonin MT₁ and MT₂ receptor subtypes. Two compounds, an acetamide and an acrylamide derivative, exhibited good binding affinities at both the human melatonin (MT) receptors and the serotonin 5‐HT_2C receptor subtype, with pK_i values of 7.96 and 7.95 against MT₁, 7.86 and 8.68 against MT2, and 6.64 and 6.44 against 5‐HT_2C, respectively.     

Nanoparticle Synthesis by Copper (II) Acetylacetonate Vapor Decomposition in the Presence of Oxygen

Crystalline nanometer-sized Cu 2 O and CuO particle formation was studied by vapor thermal decomposition of copper (II) acetylacetonate in a vertical laminar flow reactor at ambient pressure. Experiments were carried out at 3 furnace temperature profiles (maximum values of t furn = 432, 596, 705°C) and with 2 carrier gases (oxygen/nitrogen with mixture ratios of 0.5/99.5 and 10.0/90.0). The results of computational fluid dynamics simulations are presented. The introduction of oxygen into the system was found to increase the decomposition rate and removed impurities from particles. The size of produced primary particles varied from 10 to 200 nm. Particle crystallinity was found to depend on both the oxygen concentration and the furnace temperature. A model taking into account the detailed chemical reaction mechanisms during the particle formation is proposed. The model allows one to build a dynamic phase diagram of the condensed products formed during the decomposition and is in good agreement with the experimental results.     

New potential for preparation of performing h-BN coatings via polymer pyrolysis in RTA furnace

An innovative IR irradiation annealing process is used to increase the crystallization ratio of hexagonal boron nitride (h-BN) coatings on pure titanium pellets. Since the polymer pyrolysis route requires heating the green polymer at high temperature to convert it into a ceramic, the use of IR radiation furnace (compared to a resistive furnace) allows achievement of better crystallized h-BN while the substrate remains at relatively low temperature (<1000 °C). Annealing treatments have been performed under argon or nitrogen using either a halogen lamp or a Rapid Thermal Annealing (RTA) furnace. Advanced structural and chemical characterizations have shown a good chemical stability of the coatings. In addition, it has been revealed that samples annealed under Ar present a micro-composite structure at the interphase composed of a μ-layer of TiB₂/TiB/Ti(N)_x between the coating and the substrate, whereas samples annealed under nitrogen display a simpler structure at the interphase, with only TiN.     

Evaluation of alkane sulfonic acid catalysts and derivatives for curing activity in a melamine/acrylic polyol coating formulation using fourier transform infrared spectroscopy

FTIR measurements may be able to replace more laborious physical property determinations and thus serve as an efficient screening methodology in catalysis driven processes. This possibility was considered in evaluating alkane sulfonic acids catalyst performance to promote the cure of a melamine resin with acrylic polyols. The example chosen here is an evaluation of alkane sulfonic acid derivatives to measure catalytic efficiency of the cure reaction between hexamethoxymethylmelamine (HMMM) and an acrylicpolyol. The IR measurements provided information on the extent of reaction, via monitoring the disappearance of the OH stretching mode at 3472 cm⁻¹ associated with the acrylic polyol. This method may also be used to provide detailed information on reaction kinetics and insight into the cure mechanism. As the reaction proceeds, the coating’s properties change and IR measurements can serve as a probe for these changes. 900 First Ave., King of Prussia, PA 19406.