Transition-Metal Oxides/Carbides@Carbon Nanotube Composites as Multifunctional Electrocatalysts for Challenging Oxidations and Reductions

The rapid development of renewable-energy technologies such as water splitting, rechargeable metal–air batteries, and fuel cells requires highly efficient electrocatalysts capable of the oxygen-reduction reaction (ORR) and the oxygen-evolution reaction (OER). Herein, we report a facile sonication-driven synthesis to deposit the molecular manganese vanadium oxide precursor [Mn₄V₄O₁₇(OAc)₃]³⁻ on multiwalled carbon nanotubes (MWCNTs). Thermal conversion of this composite at 900 °C gives nanostructured manganese vanadium oxides/carbides, which are stably linked to the MWCNTs. The resulting composites show excellent electrochemical reactivity for ORR and OER, and significant reactivity enhancements compared with the precursors and a Pt/C reference are reported. Notably, even under harsh acidic conditions, long-term OER activity at low overpotential is reported. In addition, we report exceptional activity of the composites for the industrially important Cl₂ evolution from an aqueous HCl electrolyte. The new composite material shows how molecular deposition routes leading to highly active and stable multifunctional electrocatalysts can be developed. The facile design could in principle be extended to multiple catalyst classes by tuning of the molecular metal oxide precursor employed.     

Metal-Free Twofold Electrochemical C−H Amination of Activated Arenes: Application to Medicinally Relevant Precursor Synthesis

The efficient production of many medicinally or synthetically important starting materials suffers from wasteful or toxic precursors for the synthesis. In particular, the aromatic non-protected primary amine function represents a versatile synthetic precursor, but its synthesis typically requires toxic oxidizing agents and transition metal catalysts. The twofold electrochemical amination of activated benzene derivatives via Zincke intermediates provides an alternative sustainable strategy for the formation of new C−N bonds of high synthetic value. As a proof of concept, we use our approach to generate a benzoxazinone scaffold that gained attention as a starting structure against castrate-resistant prostate cancer. Further improvement of the structure led to significantly increased cancer cell line toxicity. Thus, exploiting environmentally benign electrooxidation, we present a new versatile and powerful method based on direct C−H activation that is applicable for example the production of medicinally relevant compounds.     

Predicting 19F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase–Inhibitor Complex

The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable ¹⁹F chemical-shift predictions to deduce ligand-binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the ¹⁹F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleeping sickness. We include many protein–inhibitor conformations as well as monomeric and dimeric inhibitor–protein complexes, thus rendering it the largest computational study on chemical shifts of ¹⁹F nuclei in a biological context to date. Our predicted shifts agree well with those obtained experimentally and pave the way for future work in this area.     

Preparation of Cationic Mixed-Mode Acrylamide-Based Monolithic Stationary Phases for Capillary Electrochromatography

A series of amphiphilic macroporous mixed-mode acrylamide-based continuous beds bearing positively charged quaternary ammonium groups is synthesized for capillary electrochromatography (CEC) under variation of the concentration of the cationic monomer in the polymerization mixture. Positively charged mixed-mode monolithic stationary phases are synthesized in pre-treated fused silica capillaries of 100 µm I.D via single step free radical copolymerization of cyclodextrin-solubilized N-tert-butylacrylamide, a hydrophilic crosslinker (piperazine diacrylamide), a hydrophilic neutral monomer (methacrylamide), and a positively charged monomer ([2-(methacryloyloxy)ethyl]trimethyl ammonium methyl sulfate) in aqueous solution containing the lyotropic salt ammonium sulfate as a pore-forming agent. The synthesized monolithic stationary phases contain hydrophobic, hydrophilic, and charged functionalities. They can be employed for the CEC separations of different classes of neutral and charged solutes (with varied polarity) in the reversed-phase mode, in the normal-phase mode, in the ion-exchange mode, in a mixed-mode, or in the hydrophilic interaction liquid chromatography (HILIC) mode. The influence of the concentration of the cationic monomer in the polymerization mixture on retention factor, electroosmotic mobility, and methylene selectivity (α_meth) is studied under isocratic conditions for alkylphenones in the reversed-phase mode by capillary electrochromatography (CEC). Scanning electron microscopy (SEM) micrographs demonstrate that the morphology of the synthesized monoliths (i.e., the domain size) is strongly influenced by the variation of the concentration of the cationic monomer in the polymerization mixture.     

Intramolecular azide-alkyne cycloaddition for the fast assembly of structurally diverse, tricyclic 1,2,3-triazoles

The synthesis of novel tricyclic 1,2,3-triazoles starting from cyclic epoxides via the sequential azidolysis, propargylation and 1,3-dipolar cycloaddition is described. Derivatization by N-arylation reaction and the synthesis of enantiomerically pure compounds is also reported. Some of these compounds exhibit significant affinity for the sigma-1 receptor.     

Synthesis of a polyrotaxane-based macroporous polymer as stationary phase for capillary electrochromatography via host-guest complexation of N,N '-ethylenedianilinediacrylamide with statistically methylated beta-cyclodextrin

A synthetic route to acrylamide-based monolithic stationary phases for CEC with rotaxane-type immobilized derivatized beta-CD was explored. N,N'-Ethylenedianilinediacrylamide was synthesized as the water-insoluble crosslinker forming water-soluble inclusion complexes with statistically methylated beta-CD. Mixed-mode stationary phases were synthesized by free radical copolymerization of the bisacrylamide-CD host-guest complex with water-soluble monomers and an additional water-soluble crosslinker in aqueous solution. Complex formation in solution and inclusion of the pseudorotaxane into the polymeric network (formation of a polyrotaxane architecture) were studied by means of (1)H-NMR chemical shift analysis, CD modified micellar EKC (CD-MEKC), 2D-NOESY spectroscopy, and solid state( 13)C-NMR spectroscopy. The presence of a mixed-mode selectivity of the stationary phase based on hydrophobic and hydrophilic interaction was confirmed by CEC with neutral polar and nonpolar solutes.     

Anti-carcinogenic effects of the flavonoid luteolin

Luteolin is a flavonoid which is part of our daily nutrition in relatively low amounts (less than 1 mg/day). Nevertheless, some epidemiological studies suggest an inverse correlation between luteolin intake and the risk of some cancer types. Luteolin displays specific anti-inflammatory and anti-carcinogenic effects, which can only partly be explained by its anti-oxidant and free radical scavenging capacities. Luteolin can delay or block the development of cancer cells in vitro and in vivo by protection from carcinogenic stimuli, by inhibition of tumor cell proliferation, by induction of cell cycle arrest and by induction of apoptosis via intrinsic and extrinsic signaling pathways. When compared to other flavonoids, luteolin was usually among the most effective ones, inhibiting tumor cell proliferation with IC(50) values between 3 and 50 microM in vitro and in vivo by 5 to 10 mg/kg i.p., intragastric application of 0.1-0.3 mg/kg/d, or as food additive in concentrations of 50 to 200 ppm. Luteolin has been shown to penetrate into human skin, making it also a candidate for the prevention and treatment of skin cancer.     

Solid-supported nitroso hetero diels-alder reactions. 2. Arylnitroso dienophiles: scope and limitations

Immobilized arylnitroso dienophiles were prepared and used in hetero Diels-Alder (HDA) reactions with a variety of dienes. Polymer-supported arylnitroso species were prepared on several linkers cleavable by different cleavage reagents and used for (i) optimization of reaction conditions for HDA reactions, (ii) evaluation of the reaction outcome with various dienes, (iii) comparison of relative reactivities of dienes, and (iv) assessment of the stability of HDA adducts toward cleavage conditions typically used in solid-phase preparation (TFA). The outcome of the HDA reactions has been evaluated for a set of 19 dienes, and the relative reactivities of dienes that yielded the expected HDA adducts were compared. Cleaved products were submitted to biological assays, and the results are reported.     

Versatile procedure for asymmetric and orthogonal protection of symmetric polyamines and its advantages for solid phase synthesis

To date, many polyamine syntheses are carried out on solid phase to allow the generation of biologically active polyamine conjugates and libraries of natural product analogs. The synthesis of compounds and libraries, which derive from a symmetric polyamine building block such as spermine requires asymmetric and orthogonal protection of the symmetric polyamine. For this purpose we have established a novel Aloc- and Nosyl-protection group strategy, which displays several advantages. Solution phase synthesis and an easy workup reveals high yield of the asymmetrically and orthogonally protected polyamine. Asymmetric protection prevents cross-linking of the resin, and sequential deprotection can occur on highly acid and base labile resins without cleavage of the linker. Finally, it tolerates the elongation and modification of the symmetric polyamine backbone with several functional groups by conventional Fukuyama-alkylation. The suitability of this protection group strategy was shown by the first solid phase synthesis of the philanthotoxin-analog HO359b.