Conversion of E4 (E4=P4, As4, AsP3) by Ni(0) and Ni(I) Synthons – A Comparative Study

The reactivity of white phosphorus and yellow arsenic towards two different nickel nacnac complexes is investigated. The nickel complexes [(L¹Ni)₂tol] ( 1 , L¹=[{N(C₆H₃ⁱPr₂-2,6)C(Me)}₂CH]⁻) and [K₂][(L¹Ni)₂(μ,η^{1 : 1}-N₂)] ( 6 ) were reacted with P₄, As₄ and the interpnictogen compound AsP₃, respectively, yielding the homobimetallic complexes [(L¹Ni)₂(μ-η²,κ¹:η²,κ¹-E₄)] (E=P ( 2 a ), As ( 2 b ), AsP₃ ( 2 c )), [(L¹Ni)₂(μ,η^{3 : 3}-E₃)] (E=P ( 3 a ), As ( 3 b )) and [K@18-c-6(thf)₂][L¹Ni(η^{1 : 1}-E₄)] (E=P ( 7 a ), As ( 7 b )), respectively. Heating of 2 a , 2 b or 2 c also leads to the formation of 3 a or 3 b . Furthermore, the reactivity of these compounds towards reduction agents was investigated, leading to [K₂][(L¹Ni)₂(μ,η^{2 : 2}-P₄)] ( 4 ) and [K@18-c-6(thf)₃][(L¹Ni)₂(μ,η^{3 : 3}-E₃)] (E=P ( 5 a ), As ( 5 b )), respectively. Compound 4 shows an unusual planarization of the initial Ni₂P₄-prism. All products were comprehensively characterized by crystallographic and spectroscopic methods.     

Ionic Organic Film Sensor for Determination of Phenolic Compounds

This paper describes the development of a new sensor based on an ionic organic film. The amphiphilic molecule, 4‐[(4‐decyloxyphenyl)‐ethynyl]‐1‐methylpyridinium iodide (10PyI), which has liquid‐crystalline properties, was synthesized and applied in the construction of a GCE/10PyI sensor. Analytical parameters for caffeic acid, repeatability (4.8 %), reproducibility (2.8 %), linearity (two ranges: 9.9×10^?7 to 3.8×10^?5 mol L^?1 and 4.7×10^?5 to 9.9×10^?5 mol L^?1) and detection limits (9.0×10^?7 mol L^?1 and 8.7×10^?6 mol L^?1), were determined. The method was successfully applied in the determination of total phenolic compounds (TPC) in mate herb extracts.     

Phosphatidylcholine‐Coated Iron Oxide Nanomicelles for In Vivo Prolonged Circulation Time with an Antibiofouling Protein Corona

We report the synthesis of micellar phosphatidylcholine‐coated superparamagnetic iron oxide nanoparticles as a new long circulation contrast agents for magnetic resonance imaging. Oleic acid‐coated Fe₃O₄ nanoparticles were first prepared through thermal degradation and then encapsulated into small clusters with a phosphatidylcholine coating to obtain hydrophilic nanomicelles. A thorough characterization confirmed the chemical nature of the coating and the excellent colloidal stability of these nanomicelles in aqueous media. Magnetization and relaxivity properties proved their suitability as magnetic resonance imaging (MRI) contrast agent and in vitro cell viability data showed low toxicity. Vascular lifetime and elimination kinetics in the liver were assessed by blood relaxometry and by in vivo MRI in rats and compared with “control” particles prepared with a polyethylene glycol derivative. These micellar particles had a lifetime in blood of more than 10 h, much longer than the control nanoparticles (≈2 h), which is remarkable considering that the coating molecule is a small biocompatible zwitterionic phospholipid. The protein corona was characterized after incubation with rat serum at different times by high‐throughput proteomics, showing a higher proportion of bound apolipoproteins and other dysopsonins for the phosphatidylcholine particles. The antibiofouling properties of this corona and its resistance to the adsorption of proteins corroborate the observed enhanced stability and prolonged systemic circulation.     

Functionalization of a cyclo‐P5 Ligand by Main‐Group Element Nucleophiles

Unprecedented functionalized products with an η⁴‐P₅ ring are obtained by the reaction of [Cp*Fe(η⁵‐P₅)] ( 1 ; Cp*=η⁵‐C₅Me₅) with different nucleophiles. With LiCH₂SiMe₃ and LiNMe₂, the monoanionic products [Cp*Fe(η⁴‐P₅CH₂SiMe₃)]^? and [Cp*Fe(η⁴‐P₅NMe₂)]^?, respectively, are formed. The reaction of 1 with NaNH₂ leads to the formation of the trianionic compound [{Cp*Fe(η⁴‐P₅)}₂N]^3?, whereas the reaction with LiPH₂ yields [Cp*Fe(η⁴‐P₅PH₂)]^? as the main product, with {[Cp*Fe(η⁴‐P₅)]₂PH}^2? as a byproduct. The calculated energy profile of the reactions provides a rationale for the formation of the different products.     

X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists

We present a robust protocol based on iterations of free energy perturbation (FEP) calculations, chemical synthesis, biophysical mapping and X-ray crystallography to reveal the binding mode of an antagonist series to the A_2A adenosine receptor (AR). Eight A_2AAR binding site mutations from biophysical mapping experiments were initially analyzed with sidechain FEP simulations, performed on alternate binding modes. The results distinctively supported one binding mode, which was subsequently used to design new chromone derivatives. Their affinities for the A_2AAR were experimentally determined and investigated through a cycle of ligand-FEP calculations, validating the binding orientation of the different chemical substituents proposed. Subsequent X-ray crystallography of the A_2AAR with a low and a high affinity chromone derivative confirmed the predicted binding orientation. The new molecules and structures here reported were driven by free energy calculations, and provide new insights on antagonist binding to the A_2AAR, an emerging target in immuno-oncology.     

Asymmetric Transfer Hydrogenation of gem-Difluorocyclopropenyl Esters: Access to Enantioenriched gem-Difluorocyclopropanes

Catalytic enantioselective access to disubstituted functionalized gem-difluorocyclopropanes, which are emerging fluorinated motifs of interest in medicinal chemistry, was achieved through asymmetric transfer hydrogenation of gem-difluorocyclopropenyl esters, catalyzed by a Noyori–Ikariya (p-cymene)-ruthenium(II) complex, with (N-tosyl-1,2-diphenylethylenediamine) as the chiral ligand and isopropanol as the hydrogen donor. The resulting cis-gem-difluorocyclopropyl esters were obtained with moderate to high enantioselectivity (ee=66–99 %), and post-functionalization reactions enable access to valuable building blocks incorporating a cis- or trans-gem-difluorocyclopropyl motif.     

A General Pathway to Heterobimetallic Triple-Decker Complexes

A systematic study on the reactivity of the triple-decker complex [(Cp’’’Co)₂(μ,η⁴:η⁴-C₇H₈)] ( A ) (Cp’’’=1,2,4-tritertbutyl-cyclopentadienyl) towards sandwich complexes containing cyclo-P₃, cyclo-P₄, and cyclo-P₅ ligands under mild conditions is presented. The heterobimetallic triple-decker sandwich complexes [(Cp*Fe)(Cp’’’Co)(μ,η⁵:η⁴-P₅)] ( 1 ) and [(Cp’’’Co)(Cp’’’Ni)(μ,η³:η³-P₃)] ( 3 ) (Cp*=1,2,3,4,5-pentamethylcyclopentadienyl) were synthesized and fully characterized. In solution, these complexes exhibit a unique fluxional behavior, which was investigated by variable temperature NMR spectroscopy. The dynamic processes can be blocked by coordination to {W(CO)₅} fragments, leading to the complexes [(Cp*Fe)(Cp’’’Co)(μ₃,η⁵:η⁴:η¹-P₅){W(CO)₅}] ( 2 a ), [(Cp*Fe)(Cp’’’Co)(μ₄,η⁵:η⁴:η¹:η¹-P₅){(W(CO)₅)₂}] ( 2 b ), and [(Cp’’’Co)(Cp’’’Ni)(μ₃,η³:η²:η¹-P₃){W(CO)₅}] ( 4 ), respectively. The thermolysis of 3 leads to the tetrahedrane complex [(Cp’’’Ni)₂(μ,η²:η²-P₂)] ( 5 ). All compounds were fully characterized using single-crystal X-ray structure analysis, NMR spectroscopy, mass spectrometry, and elemental analysis.     

Evaluation of 3D Printed Gelatin‐Based Scaffolds with Varying Pore Size for MSC‐Based Adipose Tissue Engineering

Adipose tissue engineering aims to provide solutions to patients who require tissue reconstruction following mastectomies or other soft tissue trauma. Mesenchymal stromal cells (MSCs) robustly differentiate into the adipogenic lineage and are attractive candidates for adipose tissue engineering. This work investigates whether pore size modulates adipogenic differentiation of MSCs toward identifying optimal scaffold pore size and whether pore size modulates spatial infiltration of adipogenically differentiated cells. To assess this, extrusion‐based 3D printing is used to fabricate photo‐crosslinkable gelatin‐based scaffolds with pore sizes in the range of 200–600 µm. The adipogenic differentiation of MSCs seeded onto these scaffolds is evaluated and robust lipid droplet formation is observed across all scaffold groups as early as after day 6 of culture. Expression of adipogenic genes on scaffolds increases significantly over time, compared to TCP controls. Furthermore, it is found that the spatial distribution of cells is dependent on the scaffold pore size, with larger pores leading to a more uniform spatial distribution of adipogenically differentiated cells. Overall, these data provide first insights into the role of scaffold pore size on MSC‐based adipogenic differentiation and contribute toward the rational design of biomaterials for adipose tissue engineering in 3D volumetric spaces.     

Recycling of PVC floor coverings; first results after one year of practice

Since the end of 1990, the “Arbeitsqemeinschaft PVC Bodenbelags Recycling (Society for the recycling of PVC floorings, AgPR)” collects and recycles PVC floor coverings in Germany. AgPR is an activity as well of PVC producers as of PVC floor covering manufacturers. 19 European companies participate in this venture. AgPR collects used floorings in several areas of Germany. It also pays 150 DM/t of PVC flooring delivered to its recycling plant in Großefehn. This plant has a capacity for recycling 5000 t/a. The used floor coverings are comminuted, ground to powder size and after that reused to manufacture new floor coverings.