Visible-Light Photoswitchable Benzimidazole Azo-Arenes as β-Arrestin2-Biased Selective Cannabinoid 2 Receptor Agonists

The cannabinoid 2 receptor (CB₂R) has high therapeutic potential for multiple pathogenic processes, such as neuroinflammation. Pathway-selective ligands are needed to overcome the lack of clinical success and to elucidate correlations between pathways and their respective therapeutic effects. Herein, we report the design and synthesis of a photoswitchable scaffold based on the privileged structure of benzimidazole and its application as a functionally selective CB₂R “efficacy-switch”. Benzimidazole azo-arenes offer huge potential for the broad extension of photopharmacology to a wide range of optically addressable biological targets. We used this scaffold to develop compound 10 d , a “trans-on” agonist, which serves as a molecular probe to study the β-arrestin2 (βarr2) pathway at CB₂R. βΑrr2 bias was observed in CB₂R internalization and βarr2 recruitment, while no activation occurred when looking at Gα₁₆ or mini-Gα_i. Overall, compound 10 d is the first light-dependent functionally selective agonist to investigate the complex mechanisms of CB₂R-βarr2 dependent endocytosis.     

Cross-Dehydrogenative Homocoupling of 2-Aryl-N-heterocycles and Application to the Synthesis of Phenylpyridine Borane Dimers

A method for the synthesis of 2-aryl-N-heterocyclic dimers via a cross-dehydrogenative homocoupling (homo-CDC) has been developed using commercially available Ruthenium on charcoal as catalyst and iron trichloride as oxidant. A large variety of heterocyclic scaffolds and functional groups are tolerated and a complete regioselectivity resulting from the activation of the less sterically hindered C−H bonds was observed for meta-substituted substrates. Starting from several homocoupling products obtained, a series of pyridine-borane complexes was synthesized and the impact of the dimerization on their photophysical properties was studied and rationalized using theoretical calculations.     

Micro- and Nanoscale Heterogeneities in Zeolite Beta as Measured by Atom Probe Tomography and Confocal Fluorescence Microscopy

Micro- and nanoscale information on the activating and deactivating coking behaviour of zeolite catalyst materials increases our current understanding of many industrially applied processes, such as the methanol-to-hydrocarbon (MTH) reaction. Atom probe tomography (APT) was used to reveal the link between framework and coke elemental distributions in 3D with sub-nanometre resolution. APT revealed 10–20 nanometre-sized Al-rich regions and short-range ordering (within nanometres) between Al atoms. With confocal fluorescence microscopy, it was found that the morphology of the zeolite crystal as well as the secondary mesoporous structures have a great effect on the microscale coke distribution throughout individual zeolite crystals over time. Additionally, a nanoscale heterogeneous distribution of carbon as residue from the MTH reaction was determined with carbon-rich areas of tens of nanometres within the zeolite crystals. Lastly, a short length-scale affinity between C and Al atoms, as revealed by APT, indicates the formation of carbon-containing molecules next to the acidic sites in the zeolite.     

Functional polysiloxanes. II. Neighboring effect in the hydrosilylation of poly(hydrogenmethylsiloxane‐co‐dimethylsiloxane)s by allylglycidylether

Polysiloxanes bearing epoxy groups as lateral substituents were prepared by the hydrosilylation of 1‐allyloxy‐2,3‐epoxypropane (allylglycidylether) with poly(hydrogenmethylsiloxane‐co‐dimethylsiloxane)s (D^H‐D copolymers) of various compositions. To determine the optimal conditions of the hydrosilylation catalyzed by hexachloroplatinic acid, the kinetics of the reaction were investigated for the poly(hydrogenmethylsiloxane) homopolymer. The reaction was first order in platinum, first order in double bonds, and 0.5 in SiH. This kinetic law was consistent with the hypothesis that hydrogenmethylsiloxane dyads are much more reactive than isolated units, which may be explained by the simultaneous insertion of two vicinal SiH's in a binuclear complex of platinum. This peculiar type of neighboring effect was investigated further by comparison of the kinetics of the hydrosilylation of D‐D^H copolymers of various compositions and D^H block lengths and was confirmed by the microstructure of a D‐D^H copolymer (50/50) before and after partial hydrosilylation. Triad analysis by ²⁹Si NMR showed that the resulting copolymer was not statistical but contained a high proportion of isolated SiH. This explains why hydrosilylation proceeded in two steps: a fast reaction of D^H‐D^H dyads and a slow reaction of the remaining isolated D^H units. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 837–845, 2000     

Glass Transition Temperature Depression at the Percolation Threshold in Carbon Nanotube–Epoxy Resin and Polypyrrole–Epoxy Resin Composites

Summary: The glass transition temperatures of conducting composites, obtained by blending carbon nanotubes (CNTs) or polypyrrole (PPy) particles with epoxy resin, were investigated by using both differential scanning calorimetry (DSC) and dynamical mechanical thermal analysis (DMTA). For both composites, dc and ac conductivity measurements revealed an electrical percolation threshold at which the glass transition temperature and mechanical modulus of the composites pass through a minimum.

DC conductivity, σ_dc, as a function of the conducting filler concentration of the CNT– (▪) and PPy– (○) epoxy resin composites.     

Rhodamine 101 Conjugates of Triterpenoic Amides Are of Comparable Cytotoxicity as Their Rhodamine B Analogs

Pentacyclic triterpenoic acids (betulinic, oleanolic, ursolic, and platanic acid) were selected and subjected to acetylation followed by the formation of amides derived from either piperazine or homopiperazine. These amides were coupled with either rhodamine B or rhodamine 101. All of these compounds were screened for their cytotoxic activity in SRB assays. As a result, the cytotoxicity of the parent acids was low but increased slightly upon their acetylation while a significant increase in cytotoxicity was observed for piperazinyl and homopiperazinyl amides. A tremendous improvement in cytotoxicity was observed; however, for the rhodamine B and rhodamine 101 conjugates, and compound 27, an ursolic acid derived homopiperazinyl amide holding a rhodamine 101 residue showed an EC₅₀ = 0.05 µM for A2780 ovarian cancer cells while being less cytotoxic for non-malignant fibroblasts. To date, the rhodamine 101 derivatives presented here are the first examples of triterpene derivatives holding a rhodamine residue different from rhodamine B.     

Multi-component self-assembled molecular-electronic films: towards new high-performance thermoelectric systems

The thermoelectric properties of parallel arrays of organic molecules on a surface offer the potential for large-area, flexible, solution processed, energy harvesting thin-films, whose room-temperature transport properties are controlled by quantum interference (QI). Recently, it has been demonstrated that constructive QI (CQI) can be translated from single molecules to self-assembled monolayers (SAMs), boosting both electrical conductivities and Seebeck coefficients. However, these CQI-enhanced systems are limited by rigid coupling of the component molecules to metallic electrodes, preventing the introduction of additional layers which would be advantageous for their further development. These rigid couplings also limit our ability to suppress the transport of phonons through these systems, which could act to boost their thermoelectric output, without comprising on their impressive electronic features. Here, through a combined experimental and theoretical study, we show that cross-plane thermoelectricity in SAMs can be enhanced by incorporating extra molecular layers. We utilize a bottom-up approach to assemble multi-component thin-films that combine a rigid, highly conductive ‘sticky’-linker, formed from alkynyl-functionalised anthracenes, and a ‘slippery’-linker consisting of a functionalized metalloporphyrin. Starting from an anthracene-based SAM, we demonstrate that subsequent addition of either a porphyrin layer or a graphene layer increases the Seebeck coefficient, and addition of both porphyrin and graphene leads to a further boost in their Seebeck coefficients. This demonstration of Seebeck-enhanced multi-component SAMs is the first of its kind and presents a new strategy towards the design of thin-film thermoelectric materials.

Through an experimental and theoretical study, cross-plane thermoelectricity in Self-Assembled Monolayers (SAMs) was enhanced by adding extra molecular layers, presenting a new strategy towards the design of high thermoelectric materials.     

Lanthanide-Based Probes for Imaging Detection of Enzyme Activities by NIR Luminescence,T1- and ParaCEST MRI

Applying a single molecular probe to monitor enzymatic activities in multiple, complementary imaging modalities is highly desirable to ascertain detection and to avoid the complexity associated with the use of agents of different chemical entities. We demonstrate here the versatility of lanthanide (Ln³⁺) complexes with respect to their optical and magnetic properties and their potential for enzymatic detection in NIR luminescence, CEST and T1 MR imaging, controlled by the nature of the Ln³⁺ ion, while using a unique chelator. Based on X-ray structural, photophysical, and solution NMR investigations of a family of Ln³⁺ DO3A-pyridine model complexes, we could rationalize the luminescence (Eu³⁺, Yb³⁺), CEST (Yb³⁺) and relaxation (Gd³⁺) properties and their variations between carbamate and amine derivatives. This allowed the design of $$ probes which undergo enzyme-mediated changes detectable in NIR luminescence, CEST and T1-weighted MRI, respectively governed by variations in their absorption energy, in their exchanging proton pool and in their size, thus relaxation efficacy. We demonstrate that these properties can be exploited for the visualization of β-galactosidase activity in phantom samples by different imaging modalities: NIR optical imaging, CEST and T1-weighted MRI.     

A new theoretical approach for the determination of molecular orientation persistence length of adsorbed nanofilms by FTIR reflectance spectroscopy

FTIR-Reflectance experiments have proved to be a powerful tool for the determination of molecular orientation in thin films adsorbed onto highly reflecting metals. We propose an original method for determination of the persistence length of molecular orientation in the film. This approach is based on the fact that molecular orientation persists only over a given distance from the geometrical interface. This distance is called the “persistence length of molecular orientation”. We then suppose that the nanofilm adsorbed is stratified and consists of an oriented layer (in the near-interface region) plus an isotropic one. Correlation between infrared reflection absorption band intensities and simulated band intensities allows experimentators to determine accurate molecular orientation and persistence length of orientation of a considered functional group. This is accomplished by using various IR reflection angles and p-polarization state of the incident IR wave. Film thickness and complex refractive index spectra, n(v) − i · k(v), are only needed to deduce calculated specular reflectance intensities.