Anne Susemihl  Felix Nagel  Piotr Grabarczyk  Christian A. Schmidt  Mihaela Delcea 《Molecules (Basel, Switzerland)》2021,26(24)

  相似文献   

    

Michal Fečík  Dr. Philipp N. Plessow  Prof. Felix Studt 《ChemCatChem》2021,13(10):2451-2458

The influence of the confinement imposed by eight different zeotypes on the formation of the alkoxides of 13 primary alcohols is studied using dispersion corrected density functional theory calculations with the PBE-D3 functional. Adsorption energies of the alcohols are computed along with barriers for formation of the alkoxides, which is the first step of the stepwise dehydration mechanism. We find that variations in the adsorption and transition state energies are largely governed by van der Waals interactions between substrates and the zeolite framework. Trends between different reactants, on the other hand, are largely due to the size of the molecules, which can be described quantitatively by the number of atoms constituting them. We find that the stabilization of adsorbates is largest for frameworks that are neither too small, leading to repulsive interaction, nor too spacious leading only to weak interaction.  相似文献   

    

Felix Unglaube  Dr. Carsten Robert Kreyenschulte  Dr. Esteban Mejía 《ChemCatChem》2021,13(11):2583-2591

The development of strategies for the sustainable management and valorization of agricultural waste is of outmost importance. With this in mind, we report the use of rice husk (RH) as feedstock for the preparation of heterogeneous catalysts for hydrogenation reactions. The catalysts were prepared by impregnating the milled RH with a silver nitrate solution followed by carbothermal reduction. The composition and morphology of the prepared catalysts were fully assessed by IR, AAS, ICP-MS, XPS, XRD and STEM techniques. This novel bio-genic silver-based catalysts showed excellent activity and remarkable selectivity in the hydrogenation of nitro groups in both aromatic and aliphatic substrates, even in the presence of reactive functionalities like halogens, carbonyls, borate esters or nitriles. Recycling experiments showed that the catalysts can be easily recovered and reused multiple times without significant drop in performance and without requiring re-activation.  相似文献   

    

Elaine C. Petronilho  Murilo M. Pedrote  Mayra A. Marques  Yulli M. Passos  Michelle F. Mota  Benjamin Jakobus  Gileno dos Santos de Sousa  Filipe Pereira da Costa  Adriani L. Felix  Giulia D. S. Ferretti  Fernando P. Almeida  Yraima Cordeiro  Tuane C. R. G. Vieira  Guilherme A. P. de Oliveira  Jerson L. Silva 《Chemical science》2021,12(21):7334

Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF). The mechanism of the formation of the aggregates in the nucleus remains uncertain. The present study demonstrated that the DNA-binding domain of p53 (p53C) underwent phase separation (PS) on the pathway to aggregation under various conditions. p53C phase separated in the presence of the crowding agent polyethylene glycol (PEG). Similarly, mutant p53C (M237I and R249S) underwent PS; however, the process evolved to a solid-like phase transition faster than that in the case of wild-type p53C. The data obtained by microscopy of live cells indicated that transfection of mutant full-length p53 into the cells tended to result in PS and phase transition (PT) in the nuclear compartments, which are likely the cause of the GoF effects. Fluorescence recovery after photobleaching (FRAP) experiments revealed liquid characteristics of the condensates in the nucleus. Mutant p53 tended to undergo gel- and solid-like phase transitions in the nucleus and in nuclear bodies demonstrated by slow and incomplete recovery of fluorescence after photobleaching. Polyanions, such as heparin and RNA, were able to modulate PS and PT in vitro. Heparin apparently stabilized the condensates in a gel-like state, and RNA apparently induced a solid-like state of the protein even in the absence of PEG. Conditions that destabilize p53C into a molten globule conformation also produced liquid droplets in the absence of crowding. The disordered transactivation domain (TAD) modulated both phase separation and amyloid aggregation. In summary, our data provide mechanistic insight into the formation of p53 condensates and conditions that may result in the formation of aggregated structures, such as mutant amyloid oligomers, in cancer. The pathway of mutant p53 from liquid droplets to gel-like and solid-like (amyloid) species may be a suitable target for anticancer therapy.

Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF).  相似文献   

    

Lewis R. Thomas-Hargreaves  Marcus J. Giansiracusa  Matthew Gregson  Emanuele Zanda  Felix O'Donnell  Ashley J. Wooles  Nicholas F. Chilton  Stephen T. Liddle 《Chemical science》2021,12(11):3911

Treatment of the new methanediide–methanide complex [Dy(SCS)(SCSH)(THF)] (1Dy, SCS = {C(PPh₂S)₂}²⁻) with alkali metal alkyls and auxillary ethers produces the bis-methanediide complexes [Dy(SCS)₂][Dy(SCS)₂(K(DME)₂)₂] (2Dy), [Dy(SCS)₂][Na(DME)₃] (3Dy) and [Dy(SCS)₂][K(2,2,2-cryptand)] (4Dy). For further comparisons, the bis-methanediide complex [Dy(NCN)₂][K(DB18C6)(THF)(toluene)] (5Dy, NCN = {C(PPh₂NSiMe₃)₂}²⁻, DB18C6 = dibenzo-18-crown-6 ether) was prepared. Magnetic susceptibility experiments reveal slow relaxation of the magnetisation for 2Dy–5Dy, with open magnetic hysteresis up to 14, 12, 15, and 12 K, respectively (∼14 Oe s⁻¹). Fitting the alternating current magnetic susceptibility data for 2Dy–5Dy gives energy barriers to magnetic relaxation (U_eff) of 1069(129)/1160(21), 1015(32), 1109(70), and 757(39) K, respectively, thus 2Dy–4Dy join a privileged group of SMMs with U_eff values of ∼1000 K and greater with magnetic hysteresis at temperatures >10 K. These structurally similar Dy-components permit systematic correlation of the effects of axial and equatorial ligand fields on single-molecule magnet performance. For 2Dy–4Dy, the Dy-components can be grouped into 2Dy–cation/4Dy and 2Dy–anion/3Dy, where the former have almost linear C Dy C units with short average Dy C distances, and the latter have more bent C Dy C units with longer average Dy C bonds. Both U_eff and hysteresis temperature are superior for the former pair compared to the latter pair as predicted, supporting the hypothesis that a more linear axial ligand field with shorter M–L distances produces enhanced SMM properties. Comparison with 5Dy demonstrates unusually clear-cut examples of: (i) weakening the equatorial ligand field results in enhancement of the SMM performance of a monometallic system; (ii) a positive correlation between U_eff barrier and axial linearity in structurally comparable systems.

Studies on equatorial donor and C Dy C angle variation effects on energy barriers to the slow relaxation of magnetisation are reported.  相似文献   

    

Lukas M. Müller-Wirtz  Daniel Kiefer  Joschua Knauf  Maximilian A. Floss  Jonas Doneit  Beate Wolf  Felix Maurer  Daniel I. Sessler  Thomas Volk  Sascha Kreuer  Tobias Fink 《Molecules (Basel, Switzerland)》2021,26(9)

High inspired oxygen during mechanical ventilation may influence the exhalation of the previously proposed breath biomarkers pentanal and hexanal, and additionally induce systemic inflammation. We therefore investigated the effect of various concentrations of inspired oxygen on pentanal and hexanal exhalation and serum interleukin concentrations in 30 Sprague Dawley rats mechanically ventilated with 30, 60, or 93% inspired oxygen for 12 h. Pentanal exhalation did not differ as a function of inspired oxygen but increased by an average of 0.4 (95%CI: 0.3; 0.5) ppb per hour, with concentrations doubling from 3.8 (IQR: 2.8; 5.1) ppb at baseline to 7.3 (IQR: 5.0; 10.8) ppb after 12 h. Hexanal exhalation was slightly higher at 93% of inspired oxygen with an average difference of 0.09 (95%CI: 0.002; 0.172) ppb compared to 30%. Serum IL-6 did not differ by inspired oxygen, whereas IL-10 at 60% and 93% of inspired oxygen was greater than with 30%. Both interleukins increased over 12 h of mechanical ventilation at all oxygen concentrations. Mechanical ventilation at high inspired oxygen promotes pulmonary lipid peroxidation and systemic inflammation. However, the response of pentanal and hexanal exhalation varies, with pentanal increasing by mechanical ventilation, whereas hexanal increases by high inspired oxygen concentrations.  相似文献   

    

Lukas Martin Müller-Wirtz  Daniel Kiefer  Sven Ruffing  Timo Brausch  Tobias Hüppe  Daniel I. Sessler  Thomas Volk  Tobias Fink  Sascha Kreuer  Felix Maurer 《Molecules (Basel, Switzerland)》2021,26(11)

Exhaled aliphatic aldehydes were proposed as non-invasive biomarkers to detect increased lipid peroxidation in various diseases. As a prelude to clinical application of the multicapillary column–ion mobility spectrometry for the evaluation of aldehyde exhalation, we, therefore: (1) identified the most abundant volatile aliphatic aldehydes originating from in vitro oxidation of various polyunsaturated fatty acids; (2) evaluated emittance of aldehydes from plastic parts of the breathing circuit; (3) conducted a pilot study for in vivo quantification of exhaled aldehydes in mechanically ventilated patients. Pentanal, hexanal, heptanal, and nonanal were quantifiable in the headspace of oxidizing polyunsaturated fatty acids, with pentanal and hexanal predominating. Plastic parts of the breathing circuit emitted hexanal, octanal, nonanal, and decanal, whereby nonanal and decanal were ubiquitous and pentanal or heptanal not being detected. Only pentanal was quantifiable in breath of mechanically ventilated surgical patients with a mean exhaled concentration of 13 ± 5 ppb. An explorative analysis suggested that pentanal exhalation is associated with mechanical power—a measure for the invasiveness of mechanical ventilation. In conclusion, exhaled pentanal is a promising non-invasive biomarker for lipid peroxidation inducing pathologies, and should be evaluated in future clinical studies, particularly for detection of lung injury.  相似文献   

    

Felix Duensing  Elisabeth Gruber  Paul Martini  Marcelo Goulart  Michael Gatchell  Bilal Rasul  Olof Echt  Fabio Zappa  Masoomeh Mahmoodi-Darian  Paul Scheier 《Molecules (Basel, Switzerland)》2021,26(12)

Complexes of atomic gold with a variety of ligands have been formed by passing helium nanodroplets (HNDs) through two pickup cells containing gold vapor and the vapor of another dopant, namely a rare gas, a diatomic molecule (H₂, N₂, O₂, I₂, P₂), or various polyatomic molecules (H₂O, CO₂, SF₆, C₆H₆, adamantane, imidazole, dicyclopentadiene, and fullerene). The doped HNDs were irradiated by electrons; ensuing cations were identified in a high-resolution mass spectrometer. Anions were detected for benzene, dicyclopentadiene, and fullerene. For most ligands L, the abundance distribution of AuL_n⁺ versus size n displays a remarkable enhancement at n = 2. The propensity towards bis-ligand formation is attributed to the formation of covalent bonds in Au⁺L₂ which adopt a dumbbell structure, L-Au⁺-L, as previously found for L = Xe and C₆₀. Another interesting observation is the effect of gold on the degree of ionization-induced intramolecular fragmentation. For most systems gold enhances the fragmentation, i.e., intramolecular fragmentation in AuL_n⁺ is larger than in pure L_n⁺. Hydrogen, on the other hand, behaves differently, as intramolecular fragmentation in Au(H₂)_n⁺ is weaker than in pure (H₂)_n⁺ by an order of magnitude.  相似文献   

    

Reyhaneh Armin  Sebastian Zühlke  Gisela Grunewaldt-Stcker  Felix Mahnkopp-Dirks  Souvik Kusari 《Molecules (Basel, Switzerland)》2021,26(12)

Apple Replant Disease (ARD) is a significant problem in apple orchards that causes root tissue damage, stunted plant growth, and decline in fruit quality, size, and overall yield. Dysbiosis of apple root-associated microbiome and selective richness of Streptomyces species in the rhizosphere typically concurs root impairment associated with ARD. However, possible roles of Streptomyces secondary metabolites within these observations remain unstudied. Therefore, we employed the One Strain Many Compounds (OSMAC) approach coupled to high-performance liquid chromatography-high-resolution tandem mass spectrometry (HPLC-HRMSⁿ) to evaluate the chemical ecology of an apple root-associated Streptomyces ciscaucasicus strain GS2, temporally over 14 days. The chemical OSMAC approach comprised cultivation media alterations using six different media compositions, which led to the biosynthesis of the iron-chelated siderophores, ferrioxamines. The biological OSMAC approach was concomitantly applied by dual-culture cultivation for microorganismal interactions with an endophytic Streptomyces pulveraceus strain ES16 and the pathogen Cylindrocarpon olidum. This led to the modulation of ferrioxamines produced and further triggered biosynthesis of the unchelated siderophores, desferrioxamines. The structures of the compounds were elucidated using HRMSⁿ and by comparison with the literature. We evaluated the dynamics of siderophore production under the combined influence of chemical and biological OSMAC triggers, temporally over 3, 7, and 14 days, to discern the strain’s siderophore-mediated chemical ecology. We discuss our results based on the plausible chemical implications of S. ciscaucasicus strain GS2 in the rhizosphere.  相似文献   

    

Jürgen M. Kolos  Sebastian Pomplun  Sascha Jung  Benedikt Rieß  Patrick L. Purder  Andreas M. Voll  Stephanie Merz  Monika Gnatzy  Thomas M. Geiger  Ingrid Quist-Lkken  Jerome Jatzlau  Petra Knaus  Toril Holien  Andreas Bracher  Christian Meyners  Paul Czodrowski  Vera Krewald  Felix Hausch 《Chemical science》2021,12(44):14758

Methyl groups can have profound effects in drug discovery but the underlying mechanisms are diverse and incompletely understood. Here we report the stereospecific effect of a single, solvent-exposed methyl group in bicyclic [4.3.1] aza-amides, robustly leading to a 2 to 10-fold increase in binding affinity for FK506-binding proteins (FKBPs). This resulted in the most potent and efficient FKBP ligands known to date. By a combination of co-crystal structures, isothermal titration calorimetry (ITC), density-functional theory (DFT), and 3D reference interaction site model (3D-RISM) calculations we elucidated the origin of the observed affinity boost, which was purely entropically driven and relied on the displacement of a water molecule at the protein–ligand–bulk solvent interface. The best compounds potently occupied FKBPs in cells and enhanced bone morphogenic protein (BMP) signaling. Our results show how subtle manipulation of the solvent network can be used to design atom-efficient ligands for difficult, solvent-exposed binding pockets.

Enhancement by displacement. A single methyl group displaces a water molecule from the binding site of FKBPs, resulting in the most potent binders known, outperforming the natural products FK506 and rapamycin in biochemical and cellular assays.  相似文献