Organophotocatalytic N-Demethylation of Oxycodone Using Molecular Oxygen

N-Demethylation of oxycodone is one of the key steps in the synthesis of important opioid antagonists like naloxone or analgesics like nalbuphine. The reaction is typically carried out using stoichiometric amounts of toxic and corrosive reagents. Herein, we present a green and scalable organophotocatalytic procedure that accomplishes the N-demethylation step using molecular oxygen as the terminal oxidant and an organic dye (rose bengal) as an effective photocatalyst. Optimization of the reaction conditions under continuous flow conditions using visible-light irradiation led to an efficient, reliable, and scalable process, producing noroxycodone hydrochloride in high isolated yield and purity after a simple workup.     

Synthetic and Biological Studies on New Urea and Triazole Containing Cystobactamid Derivatives

Cystobactamids belong to the group of arene-based oligoamides that effectively inhibit bacterial type IIa topoisomerases. Cystobactamid 861-2 is the most active member of these antibiotics. Most amide bonds present in the cystobactamids link benzoic acids with anilines and it was found that some of these amide bonds undergo chemical and enzymatic hydrolysis, especially the one linking ring C with ring D. This work reports on the chemical synthesis and biological evaluation of thirteen new cystobactamids that still contain the methoxyaspartate hinge. However, we exchanged selected amide bonds either by the urea or the triazole groups and modified ring A in the latter case. While hydrolytic stability could be improved with these structural substitutes, the high antibacterial potency of cystobactamid 861-2 could only be preserved in selected cases. This includes derivatives, in which the urea group is positioned between rings A and B and where the triazole is found between rings C and D.     

Evidence for Electron Transfer between Graphene and Non-Covalently Bound π-Systems

Hybridizing graphene and molecules possess a high potential for developing materials for new applications. However, new methods to characterize such hybrids must be developed. Herein, the wet-chemical non-covalent functionalization of graphene with cationic π-systems is presented and the interaction between graphene and the molecules is characterized in detail. A series of tricationic benzimidazolium salts with various steric demand and counterions was synthesized, characterized and used for the fabrication of graphene hybrids. Subsequently, the doping effects were studied. The molecules are adsorbed onto graphene and studied by Raman spectroscopy, XPS as well as ToF-SIMS. The charged π-systems show a p-doping effect on the underlying graphene. Consequently, the tricationic molecules are reduced through a partial electron transfer process from graphene, a process which is accompanied by the loss of counterions. DFT calculations support this hypothesis and the strong p-doping could be confirmed in fabricated monolayer graphene/hybrid FET devices. The results are the basis to develop sensor applications, which are based on analyte/molecule interactions and effects on doping.     

Nanoscale Organolanthanum Clusters: Nuclearity-Directing Role of Cyclopentadienyl and Halogenido Ligands

Tetramethylaluminato/halogenido(X) ligand exchange reactions in half-sandwich complexes [Cp^RLa(AlMe₄)₂] are feasible in non-coordinating solvents and provide access to large coordination clusters of the type [Cp^RLaX₂]_x. Incomplete exchange reactions generate the hexalanthanum clusters [Cp^R₆La₆X₈(AlMe₄)₄] (Cp^R=Cp*=C₅Me₅, X=I; Cp^R=Cp′=C₅H₄SiMe₃, X=Br, I). Treatment of [Cp*La(AlMe₄)₂] with two equivalents Me₃SiI gave the nonalanthanum cluster [Cp*LaI₂]₉, while the exhaustive reaction of [Cp′La(AlMe₄)₂] with the halogenido transfer reagents Me₃GeX and Me₃SiX (X=I, Br, Cl) produced a series of monocyclopentadienyl rare-earth-metal clusters with distinct nuclearity. Depending on the halogenido ion size the homometallic clusters [Cp′LaCl₂]₁₀ and [Cp′LaX₂]₁₂ (X=Br, I) could be isolated, whereas different crystallization techniques led to the aggregation of clusters of distinct structural motifs, including the desilylated cyclopentadienyl-bridged cluster [(μ-Cp)₂Cp′₈La₈I₁₄] and the heteroaluminato derivative [Cp′₁₀La₁₀Br₁₈(AlBr₂Me₂)₂]. The use of the Cp′ ancillary ligand facilitates cluster characterization by means of NMR spectroscopy.     

Bioorthogonal Turn-On BODIPY-Peptide Photosensitizers for Tailored Photodynamic Therapy

Photodynamic therapy (PDT) leads to cancer remission via the production of cytotoxic species under photosensitizer (PS) irradiation. However, concomitant damage and dark toxicity can both hinder its use. With this in mind, we have implemented a versatile peptide-based platform of bioorthogonally activatable BODIPY-tetrazine PSs. Confocal microscopy and phototoxicity studies demonstrated that the incorporation of the PS, as a bifunctional module, into a peptide enabled spatial and conditional control of singlet oxygen (¹O₂) generation. Comparing subcellular distribution, PS confined in the cytoplasmic membrane achieved the highest toxicities (IC₅₀=0.096±0.003 μm ) after activation and without apparent dark toxicity. Our tunable approach will inspire novel probes towards smart PDT.     

Enhancing Tris(pyrazolyl)borate-Based Models of Cysteine/Cysteamine Dioxygenases through Steric Effects: Increased Reactivities,Full Product Characterization and Hints to Initial Superoxide Formation

The design of biomimetic model complexes for the cysteine dioxygenase (CDO) and cysteamine dioxygenase (ADO) is reported, where the 3-His coordination of the iron ion is simulated by three pyrazole donors of a trispyrazolyl borate ligand (Tp) and protected cysteine and cysteamine represent substrate ligands. It is found that the replacement of phenyl groups—attached at the 3-positions of the pyrazole units in a previous model—by mesityl residues has massive consequences, as the latter arrange to a more spacious reaction pocket. Thus, the reaction with O₂ proceeds much faster and afterwards the first structural characterization of an iron(II) η²-O,O-sulfinate product became possible. If one of the three Tp-mesityl groups is placed in the 5-position, an even larger reaction pocket results, which leads to yet faster rates and accumulation of a reaction intermediate at low temperatures, as shown by UV/Vis and Mössbauer spectroscopy. After comparison with the results of investigations on the cobalt analogues this intermediate is tentatively assigned to an iron(III) superoxide species.     

Palladium‐Catalyzed Asymmetric [4+3]‐Cyclization Reaction of Fused 1‐Azadienes with Amino‐trimethylenemethanes: Highly Stereoselective Construction of Chiral Fused Azepines

Summary of main observation and conclusion A Pd-catalyzed asymmetric aromative[4+3]-cyclization reaction of amino-trimethylenemethanes(TMM,1d,ip3-oles)with fused 1-azadienes has been developed.This method enables access to the synthetically importance and biologically active benzofuran fused azepines and indeno-azepines in excellent efficiency and stereoselectivity(up to 95%yield,99%ee,>19:1 dr).     

Enhancement of the catalytic performances and lifetime of Ni/γ-Al2O3 catalysts for the steam toluene reforming via the combination of dopants: inspection of Cu,Co, Fe,Mn, and Mo species addition

In this work, the influence of metallic dopant addition in 10 wt % Ni/γ-Al₂O₃ catalyst on the material physico-chemical properties and catalytic activity for the toluene steam reforming was studied. Seventeen doped Ni/γ-Al₂O₃ catalysts were synthesized by the sol–gel process. The aim of this study was to determine which elements were the most suitable for the doping of 10 wt % Ni/γ-Al₂O₃ catalysts. The influence of the dopants was studied through different physico-chemical techniques. It appeared that some dopants showed lower catalytic performances due to high carbon deactivation. On the contrary, some dopants increased the resistance to coking while also improving the catalytic activity. Different mechanisms were proposed to explain these modifications of catalytic behavior. Among all doped Ni/γ-Al₂O₃ catalysts, the samples that combined Mn + Mo or Co + Mo dopants showed the best catalytic performances at 650 °C. Both samples showed high toluene reforming activity and low amounts of carbon deposit.     

A Fluorescence-Based Assay System for the Determination of Haloperoxidase-Activity Using a Two-Dimensional Calibration Ap-proach

Screening for an interesting biocatalyst and its subsequent kinetic characterization depends on a reliable activity assay. In this work, a fluorometric assay based on the halogenation of 4-methyl-7-diethylamino-coumarin was established to monitor haloperoxidase-activity. Since haloperoxidases utilize hydrogen peroxide and halide ions to halogenate a broad range of substrates by releasing hypohalous acids, a direct quantification of haloperoxidase-activity remains difficult. With the system presented here, 3-bromo-4-methyl-7-diethylaminocoumarin is preferentially formed and monitored by fluorescence measurements. As starting material and product share similar spectroscopical properties, a two-dimensional calibration ap-proach was utilized to allow for quantification of each compound within a single measurement. To validate the system, the two-dimensional Michaelis-Menten kinetics of a vanadium-dependent chloroperoxidase from Curvularia inaequalis were recorded, yielding the first overall kinetic parameters for this enzyme. With limits of detection and quantification in the low μm range, this assay may provide a reliable alternative system for the quantification of haloperoxidase-activity.     

Semiconductor Quantum Dots as Components of Photoactive Supramolecular Architectures

Luminescent quantum dots (QDs) are colloidal semiconductor nanocrystals consisting of an inorganic core covered by a molecular layer of organic surfactants. Although QDs have been known for more than thirty years, they are still attracting the interest of researchers because of their unique size-tunable optical and electrical properties arising from quantum confinement. Moreover, the controlled decoration of the QD surface with suitable molecular species enables the rational design of inorganic-organic multicomponent architectures that can show a vast array of functionalities. This minireview highlights the recent progress in the use of surface-modified QDs – in particular, those based on cadmium chalcogenides – as supramolecular platforms for light-related applications such as optical sensing, triplet photosensitization, photocatalysis and phototherapy.