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- Institut für Chemie (194) (remove)
The aim of this doctoral thesis was to establish a technique for the analysis of biomolecules with infrared matrix-assisted laser dispersion (IR-MALDI) ion mobility (IM) spectrometry. The main components of the work were the characterization of the IR-MALDI process, the development and characterization of different ion mobility spectrometers, the use of IR-MALDI-IM spectrometry as a robust, standalone spectrometer and the development of a collision cross-section estimation approach for peptides based on molecular dynamics and thermodynamic reweighting.
First, the IR-MALDI source was studied with atmospheric pressure ion mobility spectrometry and shadowgraphy. It consisted of a metal capillary, at the tip of which a self-renewing droplet of analyte solution was met by an IR laser beam. A relationship between peak shape, ion desolvation, diffusion and extraction pulse delay time (pulse delay) was established. First order desolvation kinetics were observed and related to peak broadening by diffusion, both influenced by the pulse delay. The transport mechanisms in IR-MALDI were then studied by relating different laser impact positions on the droplet surface to the corresponding ion mobility spectra. Two different transport mechanisms were determined: phase explosion due to the laser pulse and electrical transport due to delayed ion extraction. The velocity of the ions stemming from the phase explosion was then measured by ion mobility and shadowgraphy at different time scales and distances from the source capillary, showing an initially very high but rapidly decaying velocity. Finally, the anatomy of the dispersion plume was observed in detail with shadowgraphy and general conclusions over the process were drawn.
Understanding the IR-MALDI process enabled the optimization of the different IM spectrometers at atmospheric and reduced pressure (AP and RP, respectively). At reduced pressure, both an AP and an RP IR-MALDI source were used. The influence of the pulsed ion extraction parameters (pulse delay, width and amplitude) on peak shape, resolution and area was systematically studied in both AP and RP IM spectrometers and discussed in the context of the IR-MALDI process. Under RP conditions, the influence of the closing field and of the pressure was also examined for both AP and RP sources. For the AP ionization RP IM spectrometer, the influence of the inlet field (IF) in the source region was also examined. All of these studies led to the determination of the optimal analytical parameters as well as to a better understanding of the initial ion cloud anatomy.
The analytical performance of the spectrometer was then studied. Limits of detection (LOD) and linear ranges were determined under static and pulsed ion injection conditions and interpreted in the context of the IR-MALDI mechanism. Applications in the separation of simple mixtures were also illustrated, demonstrating good isomer separation capabilities and the advantages of singly charged peaks. The possibility to couple high performance liquid chromatography (HPLC) to IR-MALDI-IM spectrometry was also demonstrated. Finally, the reduced pressure spectrometer was used to study the effect of high reduced field strength on the mobility of polyatomic ions in polyatomic gases.
The last focus point was on the study of peptide ions. A dataset obtained with electrospray IM spectrometry was characterized and used for the calibration of a collision cross-section (CCS) determination method based on molecular dynamics (MD) simulations at high temperature. Instead of producing candidate structures which are evaluated one by one, this semi-automated method uses the simulation as a whole to determine a single average collision cross-section value by reweighting the CCS of a few representative structures. The method was compared to the intrinsic size parameter (ISP) method and to experimental results. Additional MD data obtained from the simulations was also used to further analyze the peptides and understand the experimental results, an advantage with regard to the ISP method. Finally, the CCS of peptide ions analyzed by IR-MALDI were also evaluated with both ISP and MD methods and the results compared to experiment, resulting in a first validation of the MD method. Thus, this thesis brings together the soft ionization technique that is IR-MALDI, which produces mostly singly charged peaks, with ion mobility spectrometry, which can distinguish between isomers, and a collision cross-section determination method which also provides structural information on the analyte at hand.
In order to provide best control of the regeneration process for each individual patient, the release of protein drugs administered during surgery may need to be timely adapted and/or delayed according to the progress of healing/regeneration. This study aims to establish a multifunctional implant system for a local on-demand release, which is applicable for various types of proteins. It was hypothesized that a tubular multimaterial container kit, which hosts the protein of interest as a solution or gel formulation, would enable on-demand release if equipped with the capacity of diameter reduction upon external stimulation. Using devices from poly(epsilon-caprolactone) networks, it could be demonstrated that a shape-memory effect activated by heat or NIR light enabled on-demand tube shrinkage. The decrease of diameter of these shape-memory tubes (SMT) allowed expelling the payload as demonstrated for several proteins including SDF-1 alpha, a therapeutically relevant chemotactic protein, to achieve e.g. continuous release with a triggered add-on dosing (open tube) or an on-demand onset of bolus or sustained release (sealed tube). Considering the clinical relevance of protein factors in (stem) cell attraction to lesions and the progress in monitoring biomarkers in body fluids, such on-demand release systems may be further explored e.g. in heart, nerve, or bone regeneration in the future.
The reaction between propargyl ethers of hydroxybenzaldehydes and the ylide ethyl (triphenylphosphoranylidene)acetate was carried out under microwave irradiation to regioselectively afford angular pyranocoumarins. The chromene and coumarin heterocyclic scaffolds were simultaneously formed in the same synthetic step without changing the reaction conditions. The natural products seselin, braylin, and dipetalolactone were among the products synthesized by this method.
This work presents two molecular fluorescent probes 1 and 2 for the selective determination of physiologically relevant K+ levels in water based on a highly K+/Na+ selective building block, the o-(2-methoxyethoxy)phenylaza-18-crown-6 lariat ether unit. Fluorescent probe 1 showed a high K+-induced fluorescence enhancement (FE) by a factor of 7.7 of the anthracenic emission and a dissociation constant (K-d) value of 38mm in water. Further, for 2+K+, we observed a dual emission behavior at 405 and 505nm. K+ increases the fluorescence intensity of 2 at 405nm by a factor of approximately 4.6 and K+ decreases the fluorescence intensity at 505nm by a factor of about 4.8. Fluorescent probe 2+K+ exhibited a K-d value of approximately 8mm in Na+-free solutions and in combined K+/Na+ solution a similar K-d value of about 9mm was found, reflecting the high K+/Na+ selectivity of 2 in water. Therefore, 2 is a promising fluorescent tool to measure ratiometrically and selectively physiologically relevant K+ levels.
Noninvasive near-infrared (NIR) light responsive therapy is a promising cancer treatment modality; however, some inherent drawbacks of conventional phototherapy heavily restrict its application in clinic. Rather than producing heat or reactive oxygen species in conventional NIR treatment, here a multifunctional yolk-shell nanoplatform is proposed that is able to generate microbubbles to destruct cancer cells upon NIR laser irradiation. Besides, the therapeutic effect is highly improved through the coalition of small interfering RNA (siRNA), which is codelivered by the nanoplatform. In vitro experiments demonstrate that siRNA significantly inhibits expression of protective proteins and reduces the tolerance of cancer cells to bubble-induced environmental damage. In this way, higher cytotoxicity is achieved by utilizing the yolk-shell nanoparticles than treated with the same nanoparticles missing siRNA under NIR laser irradiation. After surface modification with polyethylene glycol and transferrin, the yolk-shell nanoparticles can target tumors selectively, as demonstrated from the photoacoustic and ultrasonic imaging in vivo. The yolk-shell nanoplatform shows outstanding tumor regression with minimal side effects under NIR laser irradiation. Therefore, the multifunctional nanoparticles that combining bubble-induced mechanical effect with RNA interference are expected to be an effective NIR light responsive oncotherapy.
Activation of anthracene endoperoxides in leishmania and impairment of mitochondrial functions
(2018)
Leishmaniasis is a vector-borne disease caused by protozoal Leishmania. Because of resistance development against current drugs, new antileishmanial compounds are urgently needed. Endoperoxides (EPs) are successfully used in malaria therapy, and experimental evidence of their potential against leishmaniasis exists. Anthracene endoperoxides (AcEPs) have so far been only technically used and not explored for their leishmanicidal potential. This study verified the in vitro efficiency and mechanism of AcEPs against both Leishmania promastigotes and axenic amastigotes (L. tarentolae and L. donovani) as well as their toxicity in J774 macrophages. Additionally, the kinetics and radical products of AcEPs’ reaction with iron, the formation of radicals by AcEPs in Leishmania, as well as the resulting impairment of parasite mitochondrial functions were studied. Using electron paramagnetic resonance combined with spin trapping, photometry, and fluorescence-based oximetry, AcEPs were demonstrated to (i) show antileishmanial activity in vitro at IC50 values in a low micromolar range, (ii) exhibit host cell toxicity in J774 macrophages, (iii) react rapidly with iron (II) resulting in the formation of oxygen- and carbon-centered radicals, (iv) produce carbon-centered radicals which could secondarily trigger superoxide radical formation in Leishmania, and (v) impair mitochondrial functions in Leishmania during parasite killing. Overall, the data of different AcEPs demonstrate that their structures besides the peroxo bridge strongly influence their activity and mechanism of their antileishmanial action.
Phytochemical investigation of the CH2Cl2/MeOH (1:1) extract of the roots of Lannea rivae (Chiov) Sacleux (Anacardiaceae) led to the isolation of a new alkenyl cyclohexenone derivative: (4R,6S)-4,6-dihydroxy-6-((Z)-nonadec-14′-en-1-yl)cyclohex-2-en-1-one (1), and a new alkenyl cyclohexanol derivative: (2S*,4R*,5S*)-2,4,5-trihydroxy-2-((Z)-nonadec-14′-en-1-yl)cyclohexanone (2) along with four known compounds, namely epicatechin gallate, taraxerol, taraxerone and β-sitosterol; while the stem bark afforded two known compounds, daucosterol and lupeol. Similar investigation of the roots of Lannea schweinfurthii (Engl.) Engl. led to the isolation of four known compounds: 3-((E)-nonadec-16′-enyl)phenol, 1-((E)-heptadec-14′-enyl)cyclohex-4-ene-1,3-diol, catechin, and 1-((E)-pentadec-12′-enyl)cyclohex-4-ene-1,3-diol. The structures of the isolated compounds were determined by NMR spectroscopy and mass spectrometry. The absolute configuration of compound 1 was established by quantum chemical ECD calculations. In an antibacterial activity assay using the microbroth kinetic method, compound 1 showed moderate activity against Escherichia coli while compound 2 exhibited moderate activity against Staphylococcus aureus. Compound 1 also showed moderate activity against E. coli using the disc diffusion method. The roots extract of L. rivae was notably cytotoxic against both the DU-145 prostate cancer cell line and the Vero mammalian cell line (CC50 = 5.24 and 5.20 μg/mL, respectively). Compound 1 was also strongly cytotoxic against the DU-145 cell line (CC50 = 0.55 μg/mL) but showed no observable cytotoxicity (CC50 > 100 μg/mL) against the Vero cell line. The roots extract of L. rivae and L. schweinfurthii, epicatechin gallate as well as compound 1 exhibited inhibition of carageenan-induced inflammation.
Spectral density functions are central to the simulation of complex many body systems. Their determination requires making approximations not only to the dynamics but also to the underlying electronic structure theory. Here, blending different methods bears the danger of an inconsistent description. To solve this issue we propose an all-DFTB approach to determine spectral densities for the description of Frenkel excitons in molecular assemblies. The protocol is illustrated for a model of a PTCDI crystal, which involves the calculation of monomeric excitation energies and Coulomb couplings between monomer transitions, as well as their spectral distributions due to thermal fluctuations of the nuclei. Using dynamically defined normal modes, a mapping onto the standard harmonic oscillator spectral densities is achieved.
Full water splitting into hydrogen and oxygen on semiconductor nanocrystals is a challenging task; overpotentials must be overcome for both half-reactions and different catalytic sites are needed to facilitate them. Additionally, efficient charge separation and prevention of back reactions are necessary. Here, we report simultaneous H-2 and O-2 evolution by CdS nanorods decorated with nanoparticulate reduction and molecular oxidation co-catalysts. The process proceeds entirely without sacrificial agents and relies on the nanorod morphology of CdS to spatially separate the reduction and oxidation sites. Hydrogen is generated on Pt nanoparticles grown at the nanorod tips, while Ru(tpy)(bpy)Cl-2-based oxidation catalysts are anchored through dithiocarbamate bonds onto the sides of the nanorod. O-2 generation from water was verified by O-18 isotope labelling experiments, and time-resolved spectroscopic results confirmed efficient charge separation and ultrafast electron and hole transfer to the reaction sites. The system demonstrates that combining nanoparticulate and molecular catalysts on anisotropic nanocrystals provides an effective pathway for visible-light-driven photocatalytic water splitting.
Pump-probe near edge X-ray absorption fine structure (PP-NEXAFS) spectra of molecules offer insight into valence-excited states, even if optically dark. In PP-NEXAFS spectroscopy, the molecule is "pumped" by UV or visible light enforcing a valence excitation, followed by an X-ray "probe" exciting core electrons into (now) partially empty valence orbitals. Calculations of PP-NEXAFS have so far been done by costly, correlated wavefunction methods which are not easily applicable to medium-sized or large molecules. Here we propose an efficient, first principles method based on density functional theory in combination with the transition potential and Delta SCF methodology (TP-DFT/Delta SCF) to compute molecular ground state and PP-NEXAFS spectra. We apply the method to n ->pi* pump/O-K-edge NEXAFS probe spectroscopy of thymine (for which both experimental and other theoretical data exist) and to n -> pi* or pi -> pi* pump/N-K-edge NEXAFS probe spectroscopies of trans-and cis-azobenzene. Published by AIP Publishing.
Analytical epigenetics
(2018)
The field of epigenetics describes the relationship between genotype and phenotype, by regulating gene expression without changing the canonical base sequence of DNA. It deals with molecular genomic information that is encoded by a rich repertoire of chemical modifications and molecular interactions. This regulation involves DNA, RNA and proteins that are enzymatically tagged with small molecular groups that alter their physical and chemical properties. It is now clear that epigenetic alterations are involved in development and disease, and thus, are the focus of intensive research. The ability to record epigenetic changes and quantify them in rare medical samples is critical for next generation diagnostics. Optical detection offers the ultimate single-molecule sensitivity and the potential for spectral multiplexing. Here we review recent progress in ultrasensitive optical detection of DNA and histone modifications.
Different signal amplification strategies to improve the detection sensitivity of immunoassays have been applied which utilize enzymatic reactions, nanomaterials, or liposomes. The latter are very attractive materials for signal amplification because liposomes can be loaded with a large amount of signaling molecules, leading to a high sensitivity. In addition, liposomes can be used as a cell-like "bioscaffold" to directly test recognition schemes aiming at cell-related processes. This study demonstrates an easy and fast approach to link the novel hydrophobic optical probe based on [1,3]dioxolo[4,5-f]-[1,3]benzodioxole (DBD dye mm239) with tunable optical properties to hydrophilic recognition elements (e.g., antibodies) using liposomes for signal amplification and as carrier of the hydrophobic dye. The fluorescence properties of mm239 (e.g., long fluorescence lifetime, large Stokes shift, high photostability, and high quantum yield), its high hydrophobicity for efficient anchoring in liposomes, and a maleimide bioreactive group were applied in a unique combination to build a concept for the coupling of antibodies or other protein markers to liposomes (coupling to membranes can be envisaged). The concept further allowed us to avoid multiple dye labeling of the antibody. Here, anti-TAMRA-antibody (DC7-Ab) was attached to the liposomes. In proof-of-concept, steady-state as well as time-resolved fluorescence measurements (e.g., fluorescence depolarization) in combination with single molecule detection (fluorescence correlation spectroscopy, FCS) were used to analyze the binding interaction between DC7-Ab and liposomes as well as the binding of the antigen rhodamine 6G (R6G) to the antibody. Here, the Forster resonance energy transfer (FRET) between mm239 and R6G was monitored. In addition to ensemble FRET data, single-molecule FRET (PIE-FRET) experiments using pulsed interleaved excitation were used to characterize in detail the binding on a single-molecule level to avoid averaging out effects.
The CH2Cl2/MeOH (1:1) extract of the aerial parts of Tephrosia subtriflora afforded a new flavanonol, named subtriflavanonol (1), along with the known flavanone spinoflavanone B, and the known flavanonols MS-II (2) and mundulinol. The structures were elucidated by the use of NMR spectroscopy and mass spectrometry. The absolute configuration of the flavanonols was determined based on quantum chemical ECD calculations. In the antiplasmodial assay, compound 2 showed the highest activity against chloroquine-sensitive Plasmodiumfalciparum reference clones (D6 and 3D7), artemisinin-sensitive isolate (F32-TEM) as well as field isolate (KSM 009) with IC50 values 1.4-4.6M without significant cytotoxicity against Vero and HEp2 cell lines (IC50>100M). The new compound (1) showed weak antiplasmodial activity, IC50 12.5-24.2M, but also showed selective anticancer activity against HEp2 cell line (CC50 16.9M). [GRAPHICS] .
The series of novel 3,3′-bis(trisarylsilyl)- and 3,3′-bis(arylalkylsilyl)-substituted binaphtholate rare-earth-metal complexes 2a–i (SiR3 = Si(o-biphenylene)Ph (a), SiCyPh2 (b), Si-t-BuPh2 (c), Si(i-Pr)3 (d), SiCy2Ph (e), Si(2-tolyl)Ph2 (f), Si(4-t-Bu-C6H4)3 (g), Si(4-MeO-C6H4)Ph2 (h), SiBnPh2 (i)) have been prepared via arene elimination from [Ln(o-C6H4CH2NMe2)3] (Ln = Y, Lu) and the corresponding 3,3′-bis(silyl)-substituted binaphthol. The complexes exhibit high catalytic activity in the hydroamination/cyclization of aminoalkenes, with activities exceeding 1000 h–1 for (R)-2f-Ln, (R)-2g-Ln, and (R)-2h-Ln in the cyclization of 2,2-diphenylpent-4-enylamine (3a) at 25 °C, while the rigid dibenzosilole-substituted complexes (R)-2a-Ln and the triisopropylsilyl-substituted complexes (R)-2d-Ln exhibited the lowest activity in the range of 150–270 h–1. Catalysts (R)-2b-Lu, (R)-2c-Lu, (R)-2f-Lu, and (R)-2i-Lu provide the highest selectivities for the majority of the substrates, while the yttrium congeners are usually less selective. The highest enantioselectivities of 96% ee were observed using (R)-2a-Lu and (R)-2c-Lu in the cyclization of (4E)-2,2,5-triphenylpent-4-enylamine (9). The reactions show apparently zero-order rate dependence on substrate concentration and first-order rate dependence on catalyst concentration, with some reactions exhibiting a slightly accelerated rate at high conversion due to a shift in the equilibrium between a less active, higher coordinate catalyst species in favor of a more active, lower coordinate species as a result of weaker binding of the hydroamination product in comparison to the aminoalkene substrate. The shift in equilibrium from the higher to the lower coordinate species is also entropically favored at elevated temperatures, which results in an unusual increase in selectivity in the cyclization of 2,2-dimethylpent-4-enylamine (3d), presumably due to a higher selectivity of the lower coordinate catalyst species. All binaphtholate yttrium complexes, except (R)-2a-Y, are catalytically active in the intermolecular hydroamination of benzylamines with terminal alkenes. The highest selectivity of 66% ee was observed for the reaction of benzylamine with 4-phenyl-1-butene using (R)-2h-Y at 110 °C.
Asymmetric Synthesis of Nonracemic 2-Amino[6]helicenes and Their Self-Assembly into Langmuir Films
(2018)
Alternative ways of preparing nonracemic 2-amino[6]helicene derivatives were explored. The enantioselective [2 + 2 + 2] cycloisomerization of a nonchiral triyne under Ni(cod)(2)/(R)-QUINAP catalysis delivered the enantioenriched (+)-(P)-2-aminodibenzo[6]helicene derivative in 67% ee. An ultimate "point-to-helical" chirality transfer was observed in the cyclization of enantiopure triynes mediated by Ni(CO)(2)(PPh3)(2) affording (-)-(M)- or (+)-(P)-7,8-bis(p-tolyl)hexahelicen-2-amine in >99% ee as well as its benzoderivative in >99% ee. The latter mode of stereocontrol was inefficient for a 2-aminobenzo[6]helicene congener with an embedded five-membered ring. The rac-, (-)-(M)-, and (+)-(P)-7,8-bis(p-tolyl)hexahelicen-2-amines formed Langmuir monolayers at the air water interface featuring practically identical surface pressure vs mean molecular area isotherms. The corresponding Langmuir-Blodgett films on quartz or silicon substrates were characterized by UV vis/ECD spectroscopy and AFM microscopy, respectively.
Multiblock-like amphiphilic polyurethanes constituted by poly(ethylene oxide) and biosourced betulin are designed for antifouling and synthesized by a convenient organocatalytic route comprising tandem chain-growth and step-growth polymerizations. The doping density of betulin (D-B) in the polymer chain structure is readily varied by a mixed-initiator strategy. The spin-coated polymer films exhibit unique nanophase separation and protein resistance behaviors. Higher D-B leads to enhanced surface hydrophobicity and, unexpectedly, improved protein resistance. It is found that the surface holds molecular-level heterogeneity when D-B is substantially high due to restricted phase separation; therefore, broad-spectrum protein resistance is achieved despite considerable surface hydrophobicity. As D-B decreases, the distance between adjacent betulin units increases so that hydrophobic nanodomains are formed, which provide enough landing areas for relatively small-sized proteins to adsorb on the surface.
(5R,6S)-6-Acetoxy-5-hexadecanolide (MOP) is the oviposition pheromone of the mosquito Cx. quinquefasciatus, a vector of pathogens causing a variety of tropical diseases. We describe and evaluate herein three syntheses of MOP starting from mannitol-derived (3R,4R)-hexa-1,5-diene-3,4-diol. This C-2-symmetric building block is elaborated through bidirectional olefin metathesis reactions into 6-epi-MOP, which was converted into MOP via Mitsunobu inversion. The shortest of the three routes makes use of two sequential cross-metathesis reactions and an assisted tandem catalytic olefin reduction, induced by an in situ conversion of a Ru-carbene to a Ru-hydride.
Magnetische Eisenoxidnanopartikel werden bereits seit geraumer Zeit erfolgreich als MRT-Kontrastmittel in der klinischen Bildgebung eingesetzt. Durch Optimierung der magnetischen Eigenschaften der Nanopartikel kann die Aussagekraft von MR-Aufnahmen verbessert und somit der diagnostische Wert einer MR-Anwendung weiter erhöht werden. Neben der Verbesserung bestehender Verfahren wird die bildgebende Diagnostik ebenso durch die Entwicklung neuer Verfahren, wie dem Magnetic Particle Imaging, vorangetrieben. Da hierbei das Messsignal von den magnetischen Nanopartikeln selbst erzeugt wird, birgt das MPI einen enormen Vorteil hinsichtlich der Sensitivität bei gleichzeitig hoher zeitlicher und räumlicher Auflösung. Da es aktuell jedoch keinen kommerziell vertriebenen in vivo-tauglichen MPI-Tracer gibt, besteht ein dringender Bedarf an geeigneten innovativen Tracermaterialien. Daraus resultierte die Motivation dieser Arbeit biokompatible und superparamagnetische Eisenoxidnanopartikel für den Einsatz als in vivo-Diagnostikum insbesondere im Magnetic Particle Imaging zu entwickeln. Auch wenn der Fokus auf der Tracerentwicklung für das MPI lag, wurde ebenso die MR-Performance bewertet, da geeignete Partikel somit alternativ oder zusätzlich als MR-Kontrastmittel mit verbesserten Kontrasteigenschaften eingesetzt werden könnten.
Die Synthese der Eisenoxidnanopartikel erfolgte über die partielle Oxidation von gefälltem Eisen(II)-hydroxid und Green Rust sowie eine diffusionskontrollierte Kopräzipitation in einem Hydrogel.
Mit der partiellen Oxidation von Eisen(II)-hydroxid und Green Rust konnten erfolgreich biokompatible und über lange Zeit stabile Eisenoxidnanopartikel synthetisiert werden. Zudem wurden geeignete Methoden zur Formulierung und Sterilisierung etabliert, wodurch zahlreiche Voraussetzungen für eine Anwendung als in vivo-Diagnostikum geschaffen wurden. Weiterhin ist auf Grundlage der MPS-Performance eine hervorragende Eignung dieser Partikel als MPI-Tracer zu erwarten, wodurch die Weiterentwicklung der MPI-Technologie maßgeblich vorangetrieben werden könnte. Die Bestimmung der NMR-Relaxivitäten sowie ein initialer in vivo-Versuch zeigten zudem das große Potential der formulierten Nanopartikelsuspensionen als MRT-Kontrastmittel. Die Modifizierung der Partikeloberfläche ermöglicht ferner die Herstellung zielgerichteter Nanopartikel sowie die Markierung von Zellen, wodurch das mögliche Anwendungsspektrum maßgeblich erweitert wurde.
Im zweiten Teil wurden Partikel durch eine diffusionskontrollierte Kopräzipitation im Hydrogel, wobei es sich um eine bioinspirierte Modifikation der klassischen Kopräzipitation handelt, synthetisiert, wodurch Partikel mit einer durchschnittlichen Kristallitgröße von 24 nm generiert werden konnten. Die Bestimmung der MPS- und MR-Performance elektrostatisch stabilisierter Partikel ergab vielversprechende Resultate. In Vorbereitung auf die Entwicklung eines in vivo-Diagnostikums wurden die Partikel anschließend erfolgreich sterisch stabilisiert, wodurch der kolloidale Zustand in MilliQ-Wasser über lange Zeit aufrechterhalten werden konnte. Durch Zentrifugation konnten die Partikel zudem erfolgreich in verschiedene Größenfraktionen aufgetrennt werden. Dies ermöglichte die Bestimmung der idealen Aggregatgröße dieses Partikelsystems in Bezug auf die MPS-Performance.
Selenoneine, a naturally occurring form of selenium, is the selenium analogue of ergothioneine, a sulfur species with health relevance not only as a purported antioxidant but likely also beyond. Selenoneine has been speculated to exhibit similar effects. To study selenoneine's health properties as well as its metabolic transformation, the pure compound is required. Chemical synthesis of selenoneine, however, is challenging and biosynthetic approaches have been sought. We herein report the biosynthesis and isolation of selenoneine from genetically modified fission yeast Schizosaccharomyces pombe grown in a medium containing sodium selenate. After cell lysis and extraction with methanol, selenoneine was purified by three consecutive preparative reversed-phase HPLC steps. The product obtained at the mg level was characterised by high resolution mass spectrometry, NMR and HPLC/ICPMS. Biosynthesis was found to be a promising alternative to chemical synthesis, and should be suitable for upscaling to produce higher amounts of this important selenium species in the future.
The synthesis, structure, and photocatalytic water splitting performance of two new titania (TiO2)/gold(Au)/Bombyx mori silk hybrid materials are reported. All materials are monoliths with diameters of up to ca. 4.5 cm. The materials are macroscopically homogeneous and porous with surface areas between 170 and 210 m(2)/g. The diameter of the TiO2 nanoparticles (NPs) - mainly anatase with a minor fraction of brookite - and the Au NPs are on the order of 5 and 7-18 nm, respectively. Addition of poly(ethylene oxide) to the reaction mixture enables pore size tuning, thus providing access to different materials with different photocatalytic activities. Water splitting experiments using a sunlight simulator and a Xe lamp show that the new hybrid materials are effective water splitting catalysts and produce up to 30 mmol of hydrogen per 24 h. Overall the article demonstrates that the combination of a renewable and robust scaffold such as B. mori silk with a photoactive material provides a promising approach to new monolithic photocatalysts that can easily be recycled and show great potential for application in lightweight devices for green fuel production.
Flavonoids, carotenoids, and chlorophylls were characterized in microgreens and leaves of pea (Pisum sativum) and lupin (Lupinus angustifolius) as these metabolites change during ontogeny. All metabolites were higher in the leaves for both species. Acylated quercetin and kaempferol sophorotrioses were predominant in pea. Genistein and malonylated chrysoeriol were predominant in lupin. Further, the impact of breadmaking on these metabolites using pea and lupin material of two ontogenetic stages as an added ingredient in wheat-based bread was assessed. In "pea microgreen bread" no decrease of quercetin was found with regard to the non-processed plant material. However kaempferol glycosides showed slight decreases induced by the breadmaking process in "pea microgreen bread" and "pea leaf bread." In "lupin microgreen bread" no decrease of genistein compared to the non-processed plant material was found. Chrysoeriol glycosides showed slight decreases induced by the breadmaking process in "lupin microgreen bread" and "lupin leaf bread." In all breads, carotenoids and chlorophylls were depleted however pheophytin formation was caused. Thus, pea and lupin microgreens and leaves are suitable, natural ingredients for enhancing health-promoting secondary plant metabolites in bread and may even be used to tailor bread for specific consumer health needs.
Breaking the Barrier
(2018)
Topical administration permits targeted, sustained delivery of therapeutics to human skin. Delivery to the skin, however, is typically limited to lipophilic molecules with molecular weight of < 500 Da, capable of crossing the stratum corneum. Nevertheless, there are indications protein delivery may be possible in barrier deficient skin, a condition found in several inflammatory skin diseases such as psoriasis, using novel nanocarrier systems. Methods: Water in water thermo-nanoprecipitation; dynamic light scattering; zeta potential measurement; nanoparticle tracking analysis; atomic force microscopy; cryogenic transmission electron microscopy; UV absorption; centrifugal separation membranes; bicinchoninic acid assay; circular dichroism; TNF alpha binding ELISA; inflammatory skin equivalent construction; human skin biopsies; immunohistochemistry; fluorescence microscopy; western blot; monocyte derived Langerhans cells; ELISA Results: Here, we report the novel synthesis of thermoresponsive nanogels (tNG) and the stable encapsulation of the anti-TNFa fusion protein etanercept (ETR) (similar to 150 kDa) without alteration to its structure, as well as temperature triggered release from the tNGs. Novel tNG synthesis without the use of organic solvents was conducted, permitting in situ encapsulation of protein during assembly, something that holds great promise for easy manufacture and storage. Topical application of ETR loaded tNGs to inflammatory skin equivalents or tape striped human skin resulted in efficient ETR delivery throughout the SC and into the viable epidermis that correlated with clear anti-inflammatory effects. Notably, effective ETR delivery depended on temperature triggered release following topical application. Conclusion: Together these results indicate tNGs hold promise as a biocompatible and easy to manufacture vehicle for stable protein encapsulation and topical delivery into barrier-deficient skin.
Light-emitting diodes (LEDs) are considered the future of greenhouse lighting. This study investigates the carotenoid concentrations of pak choi sprouts after growth under blue, red and white LEDs at six different time points. Furthermore, the diurnal changes of RNA transcripts of key genes of the carotenoid biosynthesis pathway as well as of the carotenoid cleavage dioxygenase 4 (CCD4) gene and of the transcription factor genes elongated hypocotyl 5 (HY5) and circadian clock associated 1 (CCA1) were investigated. The carotenoid concentrations were steady throughout the day, but showed a small maximum in the afternoon. An average total carotenoid concentration of 536 +/- 29 ng mg(-1) DM produced under white LEDs was measured, which is comparable to previously described field-grown levels. The carotenoid concentrations were slightly lower under blue or red LEDs. Moreover, the diurnal RNA transcript rhythms of most of the carotenoid biosynthesis genes showed an increase during the light period, which can be correlated to the carotenoid maxima in the afternoon. Blue LEDs caused the highest transcriptional induction of biosynthetic genes as well as of CCD4, thereby indicating an increased flux through the pathway. In addition, the highest levels of HY5 transcripts and CCA1 transcripts were determined under blue LEDs.
A sodium dioctyl sulfosuccinate (AOT)/benzyl hexadecyl dimethyl ammonium chloride (BDAC) mixed micelle self-organization and adsorption on gold Au(111) surfaces have been investigated using a molecular dynamics approach. The spherical AOT/BDAC mixed micelle is strongly adsorbed on the gold surface and is disoriented to a cylinder-like shape.
Challenges in the quantification of nutrients in soils using laser-induced breakdown spectroscopy
(2018)
The quantification of the elemental content in soils with laser-induced breakdown spectroscopy (LIBS) is challenging because of matrix effects strongly influencing the plasma formation and LIBS signal. Furthermore, soil heterogeneity at the micrometre scale can affect the accuracy of analytical results. In this paper, the impact of univariate and multivariate data evaluation approaches on the quantification of nutrients in soil is discussed. Exemplarily, results for calcium are shown, which reflect trends also observed for other elements like magnesium, silicon and iron. For the calibration models, 16 certified reference soils were used. With univariate and multivariate approaches, the calcium mass fractions in 60 soils from different testing grounds in Germany were calculated. The latter approach consisted of a principal component analysis (PCA) of adequately pre-treated data for classification and identification of outliers, followed by partial least squares regression (PLSR) for quantification. For validation, the soils were also characterised with inductively coupled plasma optical emission spectroscopy (ICP OES) and X-ray fluorescence (XRF) analysis. Deviations between the LIBS quantification results and the reference analytical results are discussed.
This publication demonstrates the abilities of a precise and straightforward microcontact printing approach for the preparation of patchy silica particles. In a broad particle size range, it is possible to finely tune the number and parameters of three-dimensional patches like diameter and thickness using only polyethyleneimine ink, poly(dimethoxysilane) as stamp material and a suitable release solvent.
Bottom-up strategies for fabricating SEIRA substrates are presented. For this purpose, wet-chemically prepared gold nanoparticles are coated with a polystyrene shell and subsequently self-assembled into different nanostructures such as quasi-hexagonally ordered gold nanoparticle monolayers, double layers, and honeycomb structures. Furthermore elongated gold nanostructures are obtained by sintering of gold nanoparticle double layers. The optical properties of these different gold nanostructures are directly connected to their morphology and geometrical arrangement - leading to surface plasmon resonances from the visible to the infrared wavelength range. Finally, SEIRA enhancement factors are determined. Gold nanoparticle double layers show the best performance as SEIRA substrates.
Azobenzene-based molecular photoswitches are becoming increasingly important for the development of photoresponsive, functional soft-matter material systems. Upon illumination with light, fast interconversion between a more stable trans and a metastable cis configuration can be established resulting in pronounced changes in conformation, dipole moment or hydrophobicity. A rational design of functional photosensitive molecules with embedded azo moieties requires a thorough understanding of isomerization mechanisms and rates, especially the thermally activated relaxation. For small azo derivatives considered in the gas phase or simple solvents, Eyring’s classical transition state theory (TST) approach yields useful predictions for trends in activation energies or corresponding half-life times of the cis isomer. However, TST or improved theories cannot easily be applied when the azo moiety is part of a larger molecular complex or embedded into a heterogeneous environment, where a multitude of possible reaction pathways may exist. In these cases, only the sampling of an ensemble of dynamic reactive trajectories (transition path sampling, TPS) with explicit models of the environment may reveal the nature of the processes involved. In the present work we show how a TPS approach can conveniently be implemented for the phenomenon of relaxation–isomerization of azobenzenes starting with the simple examples of pure azobenzene and a push–pull derivative immersed in a polar (DMSO) and apolar (toluene) solvent. The latter are represented explicitly at a molecular mechanical (MM) and the azo moiety at a quantum mechanical (QM) level. We demonstrate for the push–pull azobenzene that path sampling in combination with the chosen QM/MM scheme produces the expected change in isomerization pathway from inversion to rotation in going from a low to a high permittivity (explicit) solvent model. We discuss the potential of the simulation procedure presented for comparative calculation of reaction rates and an improved understanding of activated states.
The article describes the surface modification of 3D printed poly(lactic acid) (PLA) scaffolds with calcium phosphate (CP)/gelatin and CP/chitosan hybrid coating layers. The presence of gelatin or chitosan significantly enhances CP co-deposition and adhesion of the mineral layer on the PLA scaffolds. The hydrogel/CP coating layers are fairly thick and the mineral is a mixture of brushite, octacalcium phosphate, and hydroxyapatite. Mineral formation is uniform throughout the printed architectures and all steps (printing, hydrogel deposition, and mineralization) are in principle amenable to automatization. Overall, the process reported here therefore has a high application potential for the controlled synthesis of biomimetic coatings on polymeric biomaterials.
The article describes the surface modification of 3D printed poly(lactic acid) (PLA) scaffolds with calcium phosphate (CP)/gelatin and CP/chitosan hybrid coating layers. The presence of gelatin or chitosan significantly enhances CP co-deposition and adhesion of the mineral layer on the PLA scaffolds. The hydrogel/CP coating layers are fairly thick and the mineral is a mixture of brushite, octacalcium phosphate, and hydroxyapatite. Mineral formation is uniform throughout the printed architectures and all steps (printing, hydrogel deposition, and mineralization) are in principle amenable to automatization. Overall, the process reported here therefore has a high application potential for the controlled synthesis of biomimetic coatings on polymeric biomaterials.
Recently, we proposed a small molecular inducing ligand strategy to assemble proteins into highly-ordered structures via dual non-covalent interactions, i.e. carbohydrate-protein interaction and dimerization of Rhodamine B. Using this approach, artificial protein microtubules were successfully constructed. In this study, we find that these microtubules exhibit a perfect CO2 responsiveness; assembly and disassembly of these microtubules were nicely controlled by the alternative passage of CO2 and N-2. Upon the injection of CO2, a negative net-charged SBA turns into a neutral or positive net-charged SBA, which elongated, to some extent, the effective distance between SBA and Rhodamine B, resulting in the disassociation of the Rhodamine B dimer. Further experimental and simulation results reveal that the CO2-responsive mechanism differs from that of solubility change of the previously reported CO2-responsive synthetic materials.
The thermoresponsive behavior of two diblock copolymers PS-b-PNIPAM and PS-b-PMDEGA, which both comprise a hydrophobic polystyrene (PS) block but different thermoresponsive blocks, also differing in length, poly(N-isopropylacrylamide) (PNIPAM) and poly(methoxy diethylene glycol acrylate) (PMDEGA), respectively, was comparatively investigated in a wide temperature range. Concentrated aqueous solutions containing 25 wt % polymer were studied by small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and broadband dielectric spectroscopy (BDS). DSC measurements show that, during the demixing phase transition, the hydration number per oligo(ethylene glycol) side chain in the PS-b-PMDEGA solution decreases rather gradually, even up to 20 °C above the onset of the transition, i.e., the cloud point (CP). In contrast, the PS-b-PNIPAM solution exhibits an abrupt, stepwise dehydration behavior at its CP, indicated by the sharp, narrow endothermic peak. BDS measurements suggest that the organization of the expelled water during the phase transition and the subsequent evolution of the micellar aggregates are different for the two copolymers. In the PS-b-PMDEGA solution, the long-range charge transport process changes significantly at its CP and strong interfacial polarization processes appear, probably due to charge accumulation at the interfaces between the micellar aggregates and the aqueous medium. On the contrary, in the PS-b-PNIPAM solution, the phase transition has only a marginal effect on the long-range conduction process and is accompanied by a reduction in the high-frequency (1 MHz) dielectric permittivity, ε′. The latter effect is attributed to the reduced polarization strength of local chain modes due to an enhancement of intra- and interchain hydrogen bonds (HBs) in the polymer-rich phase during the water detaching process. Surprisingly, our BDS measurements indicate that prior to both the demixing and remixing processes the local chain mobility increases temporally. Our dielectric studies suggest that for PS-b-PNIPAM the water detaching process initiates a few degrees below CP and that the local chain mobility and intra- and/or interchain HBs of the PNIPAM blocks may control its thermoresponsive behavior. Dielectric “jump” experiments show that the kinetics of micellar aggregation in the PS-b-PMDEGA solution is slower than that in the PS-b-PNIPAM solution and is independent of the target temperature within the two-phase region. From the experimental point of view, it is shown that the dielectric susceptibility, especially, the dielectric permittivity, ε′, is a well-suited probe for monitoring both the reversible changes in the molecular dipolar bond polarizability and the long-range interfacial polarization at the phase transition.
The endothelialization of synthetic surfaces applied as cardiovascular implant materials is an important issue to ensure the anti-thrombotic quality of a biomaterial. However, the rapid and constant development of a functionallycon-fluent endothelial cell monolayer is challenging. In order to investigate the compatibility of potential implant materials with endothelial cells several in vitro studies are performed. Here, glass and tissue culture plates (TCP) are often used as reference materials for in vitro pre-testing. However, a direct comparison of both substrates is lacking. Therefore, a comparison of study results is difficult, since results are often related to various reference materials. In this study, the endothelialization of glass and TCP was investigated in terms of adherence, morphology, integrity, viability and function using human umbilical vein endothelial cells (HUVEC). On both substrates an almost functionally confluent HUVEC monolayer was developed after nine days of cell seeding with clearly visible cell rims, decreased stress fiber formation and a pronounced marginal filament band. The viability of HUVEC was comparable for both substrates nine days after cell seeding with only a few dead cells. According to that, the cell membrane integrity as well as the metabolic activity showed no differences between TCP and glass. However, a significant difference was observed for the secretion of IL-6 and IL-8. The concentration of both cytokines, which are associated with migratory activity, was increased in the supernatant of HUVEC seeded on TCP. This result matches well with the slightly increased number of adherent HUVEC on TCP. In conclusion, these findings indicate that both reference materials are almost comparable and can be used equivalently as control materials in in vitro endothelialization studies.
Hypothesis: An effective way for fixating vesicle structures is the insertion of monomers and cross-linking agents into their bilayer, and their subsequent polymerization can lead to the formation of polymeric nanocapsules. Particularly attractive here are vesicle systems that form spontaneously well-defined small vesicles, as obtaining such small nanocapsules with sizes below 100 nm is still challenging. Experiments: A spontaneously forming well-defined vesicle system composed of the surfactants TDMAO (tetradecyldimethylamine oxide), Pluronic L35, and LiPFOS (lithium perfluorooctylsulfonate) mixture was used as template for fixation by polymerization. Therefore, styrene monomer was incorporated into the vesicle bilayer and ultimately these structures were fixated by UV induced radical polymerization. Structural alteration of the vesicles upon loading with monomer and the cross-linker as well as the effect of subsequent polymerization in the membrane were investigated in detail by turbidity measurements, dynamic and static light scattering, (DLS, SLS), and small angle neutron scattering (SANS). Findings: The analysis showed the changes on vesicle structures due to the monomer loading, and that these structures can become permanently fixed by the polymerization process. The potential of this approach to produce well-defined nanocapsules starting from a self-assembled system and following polymerization is critically evaluated. (C) 2018 Elsevier Inc. All rights reserved.
This project was focused on exploring the phase behavior of poly(styrene)187000-block-poly(2-vinylpyridine)203000 (SV390) with high molecular weight (390 kg/mol) in thin films, in which the self-assembly of block copolymers (BCPs) was realized via thermo-solvent annealing. The advanced processing technique of solvent vapor treatment provides controlled and stable conditions.
In Chapter 3, the factors to influence the annealing process and the swelling behavior of homopolymers are presented and discussed. The swelling behavior of BCP in films is controlled by the temperature of the vapor and of the substrate, on one hand, and variation of the saturation of the solvent vapor atmosphere (different solvents), on the other hand. Additional factors like the geometry and material of the chamber, the type of flow inside the chamber etc. also influence the reproducibility and stability of the processing. The slightly selective solvent vapor of chloroform gives 10% more swelling of P2VP than PS in films with thickness of ~40 nm.
The tunable morphology in ultrathin films of high molecular weight BCP (SV390) was investigated in Chapter 4. First, the swelling behavior can be precisely tuned by temperature and/or vapor flow separately, which provided information for exploring the multiple-parameter-influenced segmental chain mobility of polymer films. The equilibrium state of SV390 in thin films influenced by temperature was realized at various temperatures with the same degree of swelling. Various methods including characterization with SFM, metallization and RIE were used to identify the morphology of films as porous half-layer with PS dots and P2VP matrix. The kinetic investigations demonstrate that on substrates with either weak or strong interaction the original morphology of the BCP with high molecular weight is changed very fast within 5 min, and the further annealing serves for annihilation of defects.
The morphological development of symmetric BCP in films with thickness increasing from half-layer to one-layer influenced by confinement factors of gradient film thicknesses and various surface properties of substrates was studied in Chapter 5. SV390 and SV99 films show bulk lamella-forming morphology after slightly selective solvent vapor (chloroform) treatment. SV99 films show cylinder-forming morphology under strongly selective solvent vapor (toluene) treatment since the asymmetric structure (caused by toluene uptake in PS blocks only) of SV99 block copolymer during annealing. Both kinds of morphology (lamella and cylinder) are influenced by the film thickness. The annealed morphology of SV390 and SV99 influenced by the combination of confined film and substrate property is similar to the morphology on flat silicon wafers. In this chapter the gradients in the film thickness and surface properties of the substrates with regard to their influence on the morphological development in thin BCP films are presented. Directed self-assembly (graphoepitaxy) of this SV390 was also investigated to compare with systematically reported SV99.
In Chapter 6 an approach to induced oriented microphase separation in thick block copolymer films via treatment with the oriented vapor flow using mini-extruder is envisaged to be an alternative to existing methodologies, e.g. via non-solvent-induced phase separation. The preliminary tests performed in this study confirm potential perspective of this method, which alters the structure through the bulk of the film (as revealed by SAXS measurements), but more detailed studies have to be conducted in order to optimize the preparation.
Background/Aims: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. Methods: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. Results: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14:0, 16:1, and 18:1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94x10(-11)). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: - 258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). Conclusions: After correction for multiple testing and adjustment for potential confounders, LPC 16:1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies. (c) 2018 The Author(s) Published by S. Karger AG, Basel
Efficient Li utilization is generally considered to be a prerequisite for developing next-generation energy storage systems (ESSs). However, uncontrolled growth of Li microstructures (LmSs) during electrochemical cycling has prevented its practical commercialization. Herein, we attempt to understand the correlation of morphological evolution of Li electrodes with degrading electrochemical performances of Li/LiCoO2 and Li/S systems by synchrotron X-ray phase contrast tomography technique. It was found that the continuous transformation of the initial dense Li bulk to a porous lithium interface (PL1) structure intimately correlates with the gradually degrading overall cell performance of these two systems. Additionally, the formation mechanism of the PLI and its correlation with previously reported inwardly growing LmS and the lithium-reacted region have been intensively discussed. The information that we gain herein is complementary to previous investigations and may provide general insights into understanding of degradation mechanisms of Li metal anodes and also provide highly needed guidelines for effective design of reliable next-generation Li metal-based ESSs.
Aldehyde oxidases are molybdenum and flavin dependent enzymes characterized by a very wide substrate specificity and performing diverse reactions that include oxidations (e.g., aldehydes and azaheterocycles), hydrolysis of amide bonds, and reductions (e.g., nitro, S-oxides and N-oxides). Oxidation reactions and amide hydrolysis occur at the molybdenum site while the reductions are proposed to occur at the flavin site. AOX activity affects the metabolism of different drugs and xenobiotics, some of which designed to resist other liver metabolizing enzymes (e.g., cytochrome P450 monooxygenase isoenzymes), raising its importance in drug development. This work consists of a comprehensive overview on aldehyde oxidases, concerning the genetic evolution of AOX, its diversity among the human population, the crystal structures available, the known catalytic reactions and the consequences in pre-clinical pharmacokinetic and pharmacodynamic studies. Analysis of the different animal models generally used for pre-clinical trials and comparison between the human (hAOX1), mouse homologs as well as the related xanthine oxidase (XOR) are extensively considered. The data reviewed also include a systematic analysis of representative classes of molecules that are hAOX1 substrates as well as of typical and well characterized hAOX1 inhibitors. The considerations made on the basis of a structural and functional analysis are correlated with reported kinetic and metabolic data for typical classes of drugs, searching for potential structural determinants that may dictate substrate and/or inhibitor specificities.
There has been long-standing interest in developing metal oxide-based sensors with high sensitivity, selectivity, fast response and low material consumption. Here we report for the first time the utilization of Cu2O@PNIPAM core-shell microgels with a nanocube-shaped core structure for construction of novel CuO gas sensing layers. The hybrid microgels show significant improvement in colloidal stability as compared to native Cu2O nanocubes. Consequently, a homogeneous thin film of Cu2O@PNIPAM nanoparticles can be engineered in a quite low solid content (1.5 wt%) by inkjet printing of the dispersion at an optimized viscosity and surface tension. Most importantly, thermal treatment of the Cu2O@PNIPAM microgels forms porous CuO nanocubes, which show much faster response to relevant trace NO2 gases than sensors produced from bare Cu2O nanocubes. This outcome is due to the fact that the PNIPAM shell can successfully hinder the aggregation of CuO nanoparticles during pyrolysis, which enables full utilization of the sensor layers and better access of the gas to active sites. These results point out great potential of such an innovative system as gas sensors with low cost, fast response and high sensitivity.
Hexagonal p-type semiconductor CuS nanoplates were synthesized via a hot injection method from bis(trimethylsilyl) sulfide and the ionic liquid precursor bis(N-dodecylpyridinium) tetrachloridocuprate( II). The particles have a broad size distribution with diameters between 30 and 680 nm and well-developed crystal habits. The nanoplates were successfully incorporated into organic photovoltaic (OPV) cells as hole conduction materials. The power conversion efficiency of OPV cells fabricated with the nanoplates is 16% higher than that of a control device fabricated without the nanoplates. (C) 2018 Author(s).
While analyzing the fossil diatom flora in one of the longest paleolimnological records (core PI-6) from Lake Peten-Itza, lowland Guatemala, we encountered Aulacoseira Thwaites, Cyclotella (Kutzing) and Discostella (Cleve & Grunow) Houk & Klee species appearing successively in the record. Among them, two new species that are assigned to the genus Cyclotella are described herein. Cyclotella petenensis sp. nov. is characterised by a coarse striation marked by a shadow line and a tangentially undulate central area with an arc of central fultoportulae. Cyclotella cassandrae sp. nov. has an elliptically shaped valve, coarse striae and a scattered ring of central fultoportulae in the central area. Classification and differences to similar taxa in the genus Cyclotella are discussed.
We use clusters for the modeling of local ion resonances caused by low energy charge carriers in STM-induced desorption of benzene derivates from Si(111)-7 x 7. We perform Born-Oppenheimer molecular dynamics for the charged systems assuming vertical transitions to the charged states at zero temperature, to rationalize the low temperature activation energies, which are found in experiment for chlorobenzene. Our calculations suggest very similar low temperature activation energies for toluene and benzene. For the cationic resonance transitions to physisorption are found even at 0 K, while the anion remains chemisorbed during the propagations. Further, we also extend our previous static quantum chemical investigations to toluene and benzene. In addition, an in depth analysis of the ionization potentials and electron affinities, which are used to estimate resonance energies, is given.
DBD fluorescent dyes have proven to be useful in numerous applications. To widen the range of biological applications, we propose three different types of DBD molecules that have been modified in such a way that DNA interaction becomes probable. After the successful synthesis of all three compounds, we tested their fluorescent properties and their DNA binding abilities. Two of the three probes exhibit an interaction with dsDNA with subsequent fluorescence enhancement. The determined binding constants of the two new DNA dyes are comparable to other minorgroove-binding dyes. Their large Stokes shifts and their long fluorescent lifetimes are outstanding features of these dyes.
Mold fungi on malting barley grains cause major economic loss in malting and brewery facilities. Possible proxies for their detection are volatile and semivolatile metabolites. Among those substances, characteristic marker compounds have to be identified for a confident detection of mold fungi in varying surroundings. The analytical determination is usually performed through passive sampling with solid phase microextraction, gas chromatographic separation, and detection by electron ionization mass spectrometry (EI-MS), which often does not allow a confident determination due to the absence of molecular ions. An alternative is GC-APCI-MS, generally, allowing the determination of protonated molecular ions. Commercial atmospheric pressure chemical ionization (APCI) sources are based on corona discharges, which are often unspecific due to the occurrence of several side reactions and produce complex product ion spectra. To overcome this issue, an APCI source based on soft X-radiation is used here. This source facilitates a more specific ionization by proton transfer reactions only. In the first part, the APCI source is characterized with representative volatile fungus metabolites. Depending on the proton affinity of the metabolites, the limits of detection are up to 2 orders of magnitude below those of EI-MS. In the second part, the volatile metabolites of the mold fungus species Aspergillus, Alternaria, Fusarium, and Penicillium are investigated. In total, 86 compounds were found with GC-EI/APCI-MS. The metabolites identified belong to the substance classes of alcohols, aldehydes, ketones, carboxylic acids, esters, substituted aromatic compounds, terpenes, and sesquiterpenes. In addition to substances unspecific for the individual fungus species, characteristic patterns of metabolites, allowing their confident discrimination, were found for each of the 4 fungus species. Sixty-seven of the 86 metabolites are detected by X-ray-based APCI-MS alone. The discrimination of the fungus species based on these metabolites alone was possible. Therefore, APCI-MS in combination with collision induced dissociation alone could be used as a supervision method for the detection of mold fungi.
Perovskites are widely known for their enormous possibility of elemental substitution, which leads to a large variety of physical properties. Hybrid perovskites such as CH3NH3PbI3 (MAPbI(3)) and CH3NH3PbCl3 (MAPbCl(3)) are perovskites with an A([XII])B([VI)X(-)([II)(])structure, where A is an organic molecule, B is a lead(II) cation and X is a halide anion of iodine or chlorine. Whereas MAPbCl(3) crystallizes in the cubic space group Pm (3) over barm, MAPbI(3) is in the tetragonal space group I4/mcm. The substitution of I by Cl leads to an increased tolerance against humidity but is challenging or even impossible due to their large difference in ionic radii. Here, the influence of an increasing Cl content in the reaction solution on the miscibility of the solid solution members is examined systematically. Powders were synthesized by two different routes depending on the I:Cl ratio. High-resolution synchrotron X-ray data are used to establish values for the limits of the miscibility gap which are 3.1 (1.1) mol% MAPbCl(3) in MAPI(3) and 1.0 (1) mol% MAPbI(3) in MAPCl. The establishment of relations between average pseudo-cubic lattice parameters for both phases allows a determination of the degree of substitution from the observed lattice parameters.
Stepped supporting tools were developed and used in the university seminar Organic Chemistry taken by nonmajor chemistry students, which supported self-regulated learning. These supporting tools were also used for accompanying homework, which included a QR code that led to additional supporting tools. The application of stepped supporting tools in the seminars was evaluated by a four-item Likert scale. The students assessed the tools as a helpful instrument for solving tasks in chemistry.
Direkte Arylierung
(2018)
Cationic azobenzene-containing surfactants are capable of condensing DNA in solution with formation of nanosized particles that can be employed in gene delivery. The ratio of surfactant/DNA concentration and solution ionic strength determines the result of DNA-surfactant interaction: Complexes with a micelle-like surfactant associates on DNA, which induces DNA shrinkage, DNA precipitation or DNA condensation with the emergence of nanosized particles. UV and fluorescence spectroscopy, low gradient viscometry and flow birefringence methods were employed to investigate DNA-surfactant and surfactant-surfactant interaction at different NaCl concentrations, [NaCl]. It was observed that [NaCl] (or the Debye screening radius) determines the surfactant-surfactant interaction in solutions without DNA. Monomers, micelles and non-micellar associates of azobenzene-containing surfactants with head-to-tail orientation of molecules were distinguished due to the features of their absorption spectra. The novel data enabled us to conclude that exactly the type of associates (together with the concentration of components) determines the result of DNA-surfactant interaction. Predomination of head-to-tail associates at 0.01 M < [NaCl] < 0.5 M induces DNA aggregation and in some cases DNA precipitation. High NaCl concentration (higher than 0.8 M) prevents electrostatic attraction of surfactants to DNA phosphates for complex formation. DAPI dye luminescence in solutions with DNA-surfactant complexes shows that surfactant tails overlap the DNA minor groove. The addition of di- and trivalent metal ions before and after the surfactant binding to DNA indicate that the bound surfactant molecules are located on DNA in islets.
Nanophotonics is the field of science and engineering aimed at studying the light-matter interactions on the nanoscale. One of the key aspects in studying such optics at the nanoscale is the ability to assemble the material components in a spatially controlled manner. In this work, DNA origami nanostructures were used to self-assemble dye molecules and DNA coated plasmonic nanoparticles. Optical properties of dye nanoarrays, where the dyes were arranged at distances where they can interact by Förster resonance energy transfer (FRET), were systematically studied according to the size and arrangement of the dyes using fluorescein (FAM) as the donor and cyanine 3 (Cy 3) as the acceptor. The optimized design, based on steady-state and time-resolved fluorometry, was utilized in developing a ratiometric pH sensor with pH-inert coumarin 343 (C343) as the donor and pH-sensitive FAM as the acceptor. This design was further applied in developing a ratiometric toxin sensor, where the donor C343 is unresponsive and FAM is responsive to thioacetamide (TAA) which is a well-known hepatotoxin. The results indicate that the sensitivity of the ratiometric sensor can be improved by simply arranging the dyes into a well-defined array. The ability to assemble multiple fluorophores without dye-dye aggregation also provides a strategy to amplify the signal measured from a fluorescent reporter, and was utilized here to develop a reporter for sensing oligonucleotides. By incorporating target capturing sequences and multiple fluorophores (ATTO 647N dye molecules), a reporter for microbead-based assay for non-amplified target oligonucleotide sensing was developed. Analysis of the assay using VideoScan, a fluorescence microscope-based technology capable of conducting multiplex analysis, showed the DNA origami nanostructure based reporter to have a lower limit of detection than a single stranded DNA reporter. Lastly, plasmonic nanostructures were assembled on DNA origami nanostructures as substrates to study interesting optical behaviors of molecules in the near-field. Specifically, DNA coated gold nanoparticles, silver nanoparticles, and gold nanorods, were placed on the DNA origami nanostructure aiming to study surface-enhanced fluorescence (SEF) and surface-enhanced Raman scattering (SERS) of molecules placed in the hotspot of coupled plasmonic structures.
DNA origami nanostructures provide a platform where dye molecules can be arranged with nanoscale accuracy allowing to assemble multiple fluorophores without dye-dye aggregation. Aiming to develop a bright and sensitive ratiometric sensor system, we systematically studied the optical properties of nanoarrays of dyes built on DNA origami platforms using a DNA template that provides a high versatility of label choice at minimum cost. The dyes are arranged at distances, at which they efficiently interact by Forster resonance energy transfer (FRET). To optimize array brightness, the FRET efficiencies between the donor fluorescein (FAM) and the acceptor cyanine 3 were determined for different sizes of the array and for different arrangements of the dye molecules within the array. By utilizing nanoarrays providing optimum FRET efficiency and brightness, we subsequently designed a ratiometric pH nanosensor using coumarin 343 as a pH-inert FRET donor and FAM as a pH responsive acceptor. Our results indicate that the sensitivity of a ratiometric sensor can be improved simply by arranging the dyes into a well-defined array. The dyes used here can be easily replaced by other analyte-responsive dyes, demonstrating the huge potential of DNA nanotechnology for light harvesting, signal enhancement, and sensing schemes in life sciences.
The drimane sesquiterpenoids drimenin, cinnamolide, dendocarbin A, and polygodial were purified from the Canelo tree (Drimys winteri) and chemically characterized by spectroscopic methods. The pharmacological activity of these natural compounds were determined on hα4β2, hα3β4, and hα7 nicotinic acetylcholine receptors (AChRs) by Ca2+ influx measurements. The results established that drimane sesquiterpenoids inhibit AChRs with the following selectivity: hα4β2 > hα3β4 > hα7. In the case of hα4β2 AChRs, the following potency rank order was determined (IC50’s in μM): drimenin (0.97 ± 0.35) > cinnamolide (1.57 ± 0.36) > polygodial (62.5 ± 19.9) ≫ dendocarbin A (no activity). To determine putative structural features underlying the differences in inhibitory potency at hα4β2 AChRs, additional structure–activity relationship and molecular docking experiments were performed. The Ca2+ influx and structural results supported a noncompetitive mechanism of inhibition, where drimenin interacted with luminal and nonluminal (TMD-β2 intrasubunit) sites. The structure–activity relationship results, i.e., the lower the ligand polarity, the higher the inhibitory potency, supported the nonluminal interaction. Ligand binding to both sites might inhibit the hα4β2 AChR by a cooperative mechanism, as shown experimentally (nH > 1). Drimenin could be used as a molecular scaffold for the development of more potent inhibitors with higher selectivity for the hα4β2 AChR.
Based on diblock copolymers, a pair of "schizophrenic" micellar systems is designed by combining a nonionic and thermoresponsive block with a zwitterionic block, which is thermoresponsive and salt-sensitive. The nonionic block is poly(N-isopropylacrylamide) (PNIPAM) or poly(N-isopropylmethacrylamide) (PNIPMAM) and exhibits a lower critical solution temperature (LCST) behavior in aqueous solution. The zwitterionic block is a polysulfobetaine, i.e., poly(4((3-methacrylamidopropyl)dimethylammonio)butane-1-sulfonate) (PSBP), and has an upper critical solution temperature (UCST) behavior with the clearing point decreasing with increasing salt concentration. The PSBP-b-PNIPAM and PSBP-b-PNIPMAM diblock copolymers are prepared by successive reversible addition-fragmentation chain transfer (RAFT) polymerizations. The PSBP block is chosen such that the clearing point of the homopolymer is significantly higher in pure water than the cloud point of PNIPAM or PNIPMAM. Using turbidimetry, H-1 NMR, and small-angle neutron scattering, we investigate the overall phase behavior as well as the structure and interaction between the micelles and the intermediate phase, both in salt-free D2O and in 0.004 M NaBr in D2O in a wide temperature range. We find that PSBP-b-PNIPAM at 50 g L-1 in salt-free D2O is turbid in the entire temperature range. It forms spherical micelles below the cloud point of PNIPAM and cylindrical micelles above. Similar behavior is observed for PSBP-b-PNIPMAM at 50 g L-1 in salt-free D2O with a slight and smooth increase of the light transmission below the cloud point of PNIPMAM and an abrupt decrease above. Upon addition of 0.004 M NaBr, the UCST-type cloud point of the PSBP-block is notably decreased, and an intermediate regime is encountered below the cloud point of PNIPMAM, where the light transmission is slightly enhanced. In this regime, the polymer solution exhibits behavior typical for polyelectrolyte solutions. Thus, double thermosensitive and salt-sensitive behavior with "schizophrenic" micelle formation is found, and the width of the intermediate regime, where both blocks are hydrophilic, can be tuned by the addition of electrolyte.
If nanostructures are irradiated with energetic ions, the mechanism of sputtering becomes important when the ion range matches about the size of the nanoparticle. Gold nanoparticles with diameters of similar to 50 nm on top of silicon substrates with a native oxide layer were irradiated by gallium ions with energies ranging from 1 to 30 keV in a focused ion beam system. High resolution in situ scanning electron microscopy imaging permits detailed insights in the dynamics of the morphology change and sputter yield. Compared to bulk-like structures or thin films, a pronounced shaping and enhanced sputtering in the nanostructures occurs, which enables a specific shaping of these structures using ion beams. This effect depends on the ratio of nanoparticle size and ion energy. In the investigated energy regime, the sputter yield increases at increasing ion energy and shows a distinct dependence on the nanoparticle size. The experimental findings are directly compared to Monte Carlo simulations obtained from iradina and TRI3DYN, where the latter takes into account dynamic morphological and compositional changes of the target.
The effect of chain architecture on the swelling and thermal response of thin films obtained from an amphiphilic three-arm star-shaped thermo-responsive block copolymer poly(methoxy diethylene glycol acrylate)-block-polystyrene ((PMDEGA-b-PS)(3)) is investigated by in situ neutron reflectivity (NR) measurements. The PMDEGA and PS blocks are micro-phase separated with randomly distributed PS nanodomains. The (PMDEGA-b-PS)(3) films show a transition temperature (TT) at 33 degrees C in white light interferometry. The swelling capability of the (PMDEGA-b-PS)(3) films in a D2O vapor atmosphere is better than that of films from linear PS-b-PMDEGA-b-PS triblock copolymers, which can be attributed to the hydrophilic end groups and limited size of the PS blocks in (PMDEGA-b-PS)(3). However, the swelling kinetics of the as-prepared (PMDEGA-b-PS)(3) films and the response of the swollen film to a temperature change above the TT are significantly slower than that in the PS-b-PMDEGA-b-PS films, which may be related to the conformation restriction by the star-shape. Unlike in the PS-b-PMDEGA-b-PS films, the amount of residual D2O in the collapsed (PMDEGA-b-PS)(3) films depends on the final temperature. It decreases from (9.7 +/- 0.3)% to (7.0 +/- 0.3)% or (6.0 +/- 0.3)% when the final temperatures are set to 35 degrees C, 45 degrees C and 50 degrees C, respectively. This temperature-dependent reduction of embedded D2O originates from the hindrance of chain conformation from the star-shaped chain architecture.
Pak choi (Brassica rapa subsp. chinensis) is rich in secondary metabolites and contains numerous antioxidants, including flavonoids; hydroxycinnamic acids; carotenoids; chlorophylls; and glucosinolates, which can be hydrolyzed to epithionitriles, nitriles, or isothiocyanates. Here, we investigate the effect of reduced exposure to ultraviolet B (UVB) and UV (UVA and UVB) light at four different developmental stages of pak choi. We found that both the plant morphology and secondary metabolite profiles were affected by reduced exposure to UVB and UV, depending on the plant’s developmental stage. In detail, mature 15- and 30-leaf plants had higher concentrations of flavonoids, hydroxycinnamic acids, carotenoids, and chlorophylls, whereas sprouts contained high concentrations of glucosinolates and their hydrolysis products. Dry weights and leaf areas increased as a result of reduced UVB and low UV. For the flavonoids and hydroxycinnamic acids in 30-leaf plants, less complex compounds were favored, for example, sinapic acid acylated kaempferol triglycoside instead of the corresponding tetraglycoside. Moreover, also in 30-leaf plants, zeaxanthin, a carotenoid linked to protection during photosynthesis, was increased under low UV conditions. Interestingly, most glucosinolates were not affected by reduced UVB and low UV conditions. However, this study underlines the importance of 4-(methylsulfinyl)butyl glucosinolate in response to UVA and UVB exposure. Further, reduced UVB and low UV conditions resulted in higher concentrations of glucosinolate-derived nitriles. In conclusion, exposure to low doses of UVB and UV from the early to late developmental stages did not result in overall lower concentrations of plant secondary metabolites.
Remaining uremic toxins in the blood of chronic renal failure patients represent one central challenge in hemodialysis therapies. Highly porous poly(ether imide) (PEI) microparticles have been recently introduced as candidate absorber materials, which show a high absorption capacity for uremic toxins and allow hydrophilic surface modification suitable for minimization of serum protein absorption. In this work, the effects of extracts prepared from PEI microparticles modified by nucleophilic reaction with low molecular weight polyethylene imine (Pei) or potassium hydroxide (KOH), on human monocytic (THP-1) cells are studied. The obtained results suggested that the extracts of Pei and KOH modified PEI absorbers have no negative effect on THP-1 cell viability and do not initiate the critical differentiation towards macrophages. The extracts did not enhance transcript or protein levels of investigated proinflammatory markers in THP-1 cells, namely, TNF alpha, MCP1, IL6 and IL8. Based on these findings such modified PEI microparticles should be qualified for further pre-clinical evaluation i.e. in an in vivo animal experiment.
Mit einer ausgewogenen Stoffauswahl aus den Teilgebieten Chemische Thermodynamik, Reaktionskinetik und Elektrochemie wird der Leser an das Studium der Physikalischen Chemie herangeführt. Das Verständnis der Theorie wird durch zahlreiche Aufgabenstellungen und die Angabe ihrer Lösungswege erleichtert. Das Buch gibt dem Studenten darüber hinaus Anregungen für ausgewählte Experimente zu den behandelten Teilgebieten, mit denen sich ein Grundverständnis physikalisch-chemischer Zusammenhänge entwickeln lässt.
In order to replace bio-macromolecules by stable synthetic materials in separation techniques and bioanalysis biomimetic receptors and catalysts have been developed: Functional monomers are polymerized together with the target analyte and after template removal cavities are formed in the "molecularly imprinted polymer" (MIP) which resemble the active sites of antibodies and enzymes. Starting almost 80 years ago, around 1,100 papers on MIPs were published in 2016. Electropolymerization allows to deposit MIPs directly on voltammetric electrodes or chips for quartz crystal microbalance (QCM) and surface plasmon resonance (SPR). For the readout of MIPs for drugs amperometry, differential pulse voltammetry (DPV) and impedance spectroscopy (EIS) offer higher sensitivity as compared with QCM or SPR. Application of simple electrochemical devices allows both the reproducible preparation of MIP sensors, but also the sensitive signal generation. Electrochemical MIP-sensors for the whole arsenal of drugs, e.g. the most frequently used analgesics, antibiotics and anticancer drugs have been presented in literature and tested under laboratory conditions. These biomimetic sensors typically have measuring ranges covering the lower nano-up to millimolar concentration range and they are stable under extreme pH and in organic solvents like nonaqueous extracts.
The complex formation of the following diazaperylene ligands (L) 1,12-diazaperylene 1, 1,1-bisisoquinoline 2, 2,11-disubstituted 1,12-diazaperylenes (alkyl=methyl, ethyl, isopropyl, 3, 5, 7), 3,3-disubstituted 1,1-bisisoquinoline (alkyl=methyl, ethyl, isopropyl, 4, 6, 8 and with R=phenyl, 11 and with pyridine 12), and the 5,8-dimethoxy-substituted diazaperylene 9, 6,6-dimethoxy-substituted bisisoquinoline 10 with AgBF4 was investigated. Collision-induced dissociation measurements were used to evaluate the relative stabilities of the ligands themselves and for the [1:1](+) complexes as well as for the homoleptic and heteroleptic silver [1:2](+) complexes in the gas phase. This method is very useful in rapid screening of the stabilities of new complexes in the gas phase. The influence of the spatial arrangement of the ligands and the type of substituents employed for the complexation were examined. The effect of the preorganization of the diazaperylene on the threshold activation voltages and thus of the relative binding energies of the different complexes are discussed. Density functional theory calculations were used to calculate the optimized structures of the silver complexes and compared with the stabilities of the complexes in the gas phase for the first time.
Metal-free entropy-driven disulfide metathesis polymerization of unsaturated L-cystine based macrocycles produces high-molar-mass heterofunctional poly(disulfide)s, i.e., poly(ester-disulfide-alkene) and poly(amide-disulfide-alkene); M-w(app) = 44-60 kDa, (sic) > 1.7. The polymerization is fast and reaches equilibrium within 1-5 minutes (monomer conversion 70-90%) in polar aprotic solvents such as N,N-dimethylacetamide, dimethylsulfoxide, or y-valerolactone. Thiol-terminated polymers are stable in bulk or when dissolved in weakly polar solvents, but rapidly depolymerize in dilute polar solution.
In dieser Arbeit steht die Entwicklung einer Sensorplattform für biochemische Anwendungen, welche auf einem optischen Detektionsprinzips beruht, im Vordergrund. Während der Entwicklung wurden zwei komplementäre Konzeptideen behandelt, zum einen ein Sensor, der auf photonischen Kristallen und Wellenleiterstrukturen basiert und zum anderen einen faserbasierten Sensor, der chemisch modifizierte Faser-Bragg-Gitter enthält. Das optische Detektionsprinzip in beiden Sensorideen ist die resultierende Brechungsindexänderung als messbare physikochemische Kenngröße.
Das aus der Natur bekannte Phänomen der photonischen Kristalle, das u. a. bei Opalen und bei Schmetterlingen zu finden ist, wurde bereits 1887 von Lord Rayleigh beschrieben. Er beschrieb die optischen Eigenschaften von periodischen mehrschichtigen Filmen, welche als vereinfachtes Modell eines eindimensionalen photonischen Kristalls verstanden werden können. Die Periodizität der Brechungsindexänderung resultiert in einem optischen Filter für Frequenzen in einem bestimmten spektralen Bereich, weshalb dann dort keine Lichtausbreitung mehr möglich ist. Wird dieses System aber durch eine Defektstelle in der Brechungsindexperiodizität gestört, sodass daraus zwei perfekt periodische Systeme entstehen, ist die Lichtausbreitung für eine bestimmte Frequenz dennoch möglich. In der Folge resultiert daraus ein schmalbandiges Signal im Transmissionsspektrum. Die erlaubte Frequenz ist dabei u. a. abhängig vom Brechungsindexunterschied des periodischen Systems, d.h. Veränderung des Brechungsindexes einer Schicht führt zu einer spektralen Verschiebung der erlaubten Frequenz, dadurch kann dieses Sensorkonzept für biochemische Sensorik ausgenutzt werden [1]. Diese Entwicklung des auf photonischen Kristallen basierenden Sensors war eine Kooperation mit dem Industriepartner „Nanoplus GmbH“. In der Doktorarbeit wurden Simulationen und praktischen Arbeiten zur Designentwicklung des Sensors und die Arbeiten an einem ersten Modellaufbau für die biochemischen Anwendungen durchgeführt.
Für den faserbasierten Sensor wurden Faser-Bragg-Gitter in den Faserkern hineingeschrieben. Hill et al. entdeckten 1978, dass solche Gitterstrukturen genau wie photonische Kristalle als optische Filter fungieren [2]. Die Gitter bestehen dabei aus Änderungen des Brechungsindexes im Faserkern. Im Laufe der nächsten vierzig Jahren wurden verschiedene Einschreibetechniken und Gitterstrukturen entwickelt, weshalb die Eigenschaften der jeweiligen Gitterstrukturen variieren. Eine solche Gitterstruktur sind u. a. die Faser-Bragg-Gitter, deren Gitterperiode, d. h. die Abstände der Brechungsindexmodifikationen, sich im Nanometer- bis Mikrometerbereich befinden. Aufgrund der kleinen Gitterperiode wird eine rückwärtsführende Welle im Kern für eine bestimmte Frequenz bzw. Wellenlänge, der Bragg-Wellenlänge, erzeugt. Im Endeffekt resultiert daraus ein schmalbandiges Signal sowohl im Transmissionsspektrum, als auch im Reflexionsspektrum. Die Resonanzwellenlänge ist dabei proportional zu der Gitterperiode und dem effektiven Brechungsindex, welcher vom Brechungsindex des Kerns und des kernumgebenen Materials abhängig ist. Letztlich eignet sich diese Technik für physikochemische Sensorik. Im Rahmen dieser Arbeit wurden die Gitter mit Hilfe einer relativen neuen Herstellungsmethode in die Fasern geschrieben [3]. Anschließend stand die Entwicklung eines Biosensors im Vordergrund, wobei zunächst ein Protokoll zum Ätzen der Faser mit Flusssäure entwickelt worden ist, dass das System sensitiv zum umgebenen Brechungsindex macht. Am Ende wurde ein Modellaufbau realisiert, indem ein Modellsystem, hier die Detektion vom C-reaktiven Protein mittels spezifischen einzelsträngigen DNS-Aptameren, erfolgreich getestet und quantifiziert worden ist.
1 Mandal, S.; Erickson, D. Nanoscale Optofluidic Sensor Arrays. Opt. Express 2008, 16 (3), 1623–1631.
2 Hill, K. O.; Fujii, Y.; Johnson, D. C.; Kawasaki, B. S. Photosensitivity in Optical Fiber Waveguides: Application to Reflection Filter Fabrication. Appl. Phys. Lett. 1978, 32 (10), 647–649.
3 Martínez, A.; Dubov, M.; Khrushchev, I.; Bennion, I. Direct Writing of Fibre Bragg Gratings by Femtosecond Laser. Electron. Lett. 2004, 40 (19), 1170.
Die intrazelluläre Markierung mit geeigneten Reagenzien ermöglicht ihre bildgebende Darstellung in lebenden Organismen. Dieses Verfahren (auch „Zell-Tracking“ genannt) wird in der Grundlagenforschung zur Entwicklung zellulärer Therapien, für die Erforschung pathologischer Prozesse, wie der Metastasierung, sowie für Therapiekontrollen eingesetzt. Besondere Bedeutung haben in den letzten Jahren zelluläre Therapien mit Stammzellen erlangt, da sie großes Potential bei der Regeneration von Geweben bei Krankheiten wie Morbus Parkinson oder Typ-1-Diabetes versprechen. Für die Entwicklung einer zellulären Therapie sind Informationen über den Verbleib der applizierten Zellen in vivo (Homing-Potential), über ihre Zellphysiologie sowie über die Entstehung möglicher Entzündungen notwendig. Das Ziel der vorliegenden Arbeit war daher die Synthese von Markierungsreagenzien, die nicht nur eine effiziente Zellmarkierung ermöglichen, sondern einen synergistischen Effekt hinsichtlich des modalitätsübergreifenden Einsatzes in den bildgebenden Verfahren MRT und Laser-Ablation(LA)-ICP-MS erlauben. Die MRT-Bildgebung ermöglicht die nicht invasive Nachverfolgung markierter Zellen in vivo und die LA-ICP-MS die anschließende ex vivo Analytik zur Darstellung der Elementverteilung (Bioimaging) in einer Biopsieprobe oder in einem Gewebeschnitt. Für diese Zwecke wurden zwei verschiedene Markierungsreagenzien mit dem kontrastgebenden Element Gadolinium synthetisiert. Gadolinium eignet sich aufgrund seines hohen magnetischen Moments hervorragend für die MRT-Bildgebung und da es in Biomolekülen nicht natürlich vorkommt, konnten die Reagenzien gleichermaßen für die Zellmarkierung und das Bioimaging mit der LA-ICP-MS untersucht werden. Für die Synthese eines makromolekularen Reagenzes wurde das kommerziell verfügbare Dendrimer G5-PAMAM über bifunktionelle Linker mit dem Chelator DOTA funktionalisiert, um anschließend Gadolinium zu komplexieren. Ein zweites, nanopartikuläres Reagenz wurde über eine Solvothermal-Synthese erhalten, bei der Ln:GdVO4-Nanokristalle mit einer funktionellen Polyacrylsäure(PAA)-Hülle dargestellt wurden. Die Dotierung der Ln:GdVO4-PAA Nanokristalle mit verschiedenen Lanthanoiden (Ln=Eu, Tb) zeigte ihre prinzipielle Multiplexfähigkeit in der LA-ICP-MS. Beide Markierungsreagenzien zeichneten sich durch gute Bioverträglichkeiten und r1-Relaxivitäten aus, was zudem ihr Potential für Anwendungen als präklinische „blood-pool“ MRT-Kontrastmittel belegte. Die Untersuchung der Zellmarkierung erfolgte anhand einer Tumorzelllinie und einer Stammzelllinie, wobei beide Zellarten erfolgreich intrazellulär mit beiden Reagenzien markiert wurden. Nach der Zellmarkierung veranschaulichte die in vitro MRT-Bildgebung von Zell-Phantomen eine deutlichere Kontrastverstärkung der Zellen nach der Markierung mit den Nanokristallen im Vergleich zum kommerziellen Kontrastmittel Magnevist®. Die hohe Effizienz der Zellmarkierung mit den Nanokristallen und die damit verbundenen hohen Signalintensitäten in einer einzelnen Zelle erlaubten beim Bioimaging mit der LA-ICP-MS, Messungen bis zu einer Auflösung von 4 µm Laser Spot Size. Nach der Zellmarkierung mit den DOTA(Gd3+)-funktionalisierten G5-PAMAM Dendrimeren waren hingegen Aufnahmen mit der LA-ICP-MS nur bis zu einer Auflösung von 12 µm Laser Spot Size möglich. Insgesamt waren die Ln:GdVO4-PAA Nanokristalle mit größerer Ausbeute und kostengünstiger herstellbar als die DOTA(Gd3+)-funktionalisierten G5-PAMAM Dendrimere und zeigten zudem eine effizientere Zellmarkierung. Die Ln:GdVO4-PAA Nanokristalle erscheinen somit für das Zell-Tracking als besonders vielversprechend. Darauf aufbauend wurden die Nanokristalle zur Etablierung der Antikörper-Konjugation ausgewählt, was sie für die molekulare in vivo Bildgebung sowie für die Immuno-Bildgebung von Gewebeschnitten oder Biopsie-Proben mit der LA-ICP-MS anwendbar macht.
Despite the rapid development of Pickering interfacial catalysis (PIC) at liquid-liquid interfaces with chemocatalysts, the use of unstable biocatalysts at emulsion interfaces remains a technical challenge. Herein, we present a Pickering interfacial biocatalysis (PIB) platform based on robust and recyclable enzyme-polymer conjugates that act as both catalytic sites and stabilizers at the interface of Pickering emulsions. The conjugates were prepared by growing poly(N-isopropylacrylamide) on a fragile enzyme, benzaldehyde lyase, under physiological conditions. The mild in situ conjugation process preserved the enzyme structure, and the conjugates were used to emulsify a water-organic two-phase system into a stable Pickering emulsion, leading to a significantly larger interfacial area and a 270-fold improvement in catalytic performance as compared to the unemulsified two-phase system. The PIB system could be reused multiple times. Conjugates of other enzymes were also fabricated and applied for cascade reactions.
Boric acid and sodium borates are currently classified in the EU-CLP regulation as "toxic to reproduction" under "Category 1B", with hazard statement of H360FD. However, so far field studies on male reproduction in China and in Turkey could not confirm such boron-associated toxic effects. As validation by another independent study is still required, the present study has investigated possible boron-associated effects on male reproduction in workers (n = 212) under different boron exposure conditions. The mean daily boron exposure (DBE) and blood boron concentration of workers in the extreme exposure group (n = 98) were 47.17 +/- 17.47 (7.95-106.8) mg B/day and 570.6 +/- 160.1 (402.6-1100) ng B/g blood, respectively. Nevertheless, boron-associated adverse effects on semen parameters, as well as on FSH, LH and total testosterone levels were not seen, even within the extreme exposure group. With this study, a total body of evidence has accumulated that allows to conclude that male reproductive effects are not relevant to humans, under any feasible and realistic conditions of exposure to inorganic boron compounds.
The hydrolytic stability of polymers to be used for coatings in aqueous environments, for example, to confer anti-fouling properties, is crucial. However, long-term exposure studies on such polymers are virtually missing. In this context, we synthesized a set of nine polymers that are typically used for low-fouling coatings, comprising the well-established poly(oligoethylene glycol methylether methacrylate), poly(3-(N-2-methacryloylethyl-N,N-dimethyl) ammoniopropanesulfonate) (“sulfobetaine methacrylate”), and poly(3-(N-3-methacryamidopropyl-N,N-dimethyl)ammoniopropanesulfonate) (“sulfobetaine methacrylamide”) as well as a series of hitherto rarely studied polysulfabetaines, which had been suggested to be particularly hydrolysis-stable. Hydrolysis resistance upon extended storage in aqueous solution is followed by ¹H NMR at ambient temperature in various pH regimes. Whereas the monomers suffered slow (in PBS) to very fast hydrolysis (in 1 M NaOH), the polymers, including the polymethacrylates, proved to be highly stable. No degradation of the carboxyl ester or amide was observed after one year in PBS, 1 M HCl, or in sodium carbonate buffer of pH 10. This demonstrates their basic suitability for anti-fouling applications. Poly(sulfobetaine methacrylamide) proved even to be stable for one year in 1 M NaOH without any signs of degradation. The stability is ascribed to a steric shielding effect. The hemisulfate group in the polysulfabetaines, however, was found to be partially labile.
The hydrolytic stability of polymers to be used for coatings in aqueous environments, for example, to confer anti-fouling properties, is crucial. However, long-term exposure studies on such polymers are virtually missing. In this context, we synthesized a set of nine polymers that are typically used for low-fouling coatings, comprising the well-established poly(oligoethylene glycol methylether methacrylate), poly(3-(N-2-methacryloylethyl-N,N-dimethyl) ammoniopropanesulfonate) (sulfobetaine methacrylate), and poly(3-(N-3-methacryamidopropyl-N,N-dimethyl)ammoniopropanesulfonate) (sulfobetaine methacrylamide) as well as a series of hitherto rarely studied polysulfabetaines, which had been suggested to be particularly hydrolysis-stable. Hydrolysis resistance upon extended storage in aqueous solution is followed by H-1 NMR at ambient temperature in various pH regimes. Whereas the monomers suffered slow (in PBS) to very fast hydrolysis (in 1 M NaOH), the polymers, including the polymethacrylates, proved to be highly stable. No degradation of the carboxyl ester or amide was observed after one year in PBS, 1 M HCl, or in sodium carbonate buffer of pH 10. This demonstrates their basic suitability for anti-fouling applications. Poly(sulfobetaine methacrylamide) proved even to be stable for one year in 1 M NaOH without any signs of degradation. The stability is ascribed to a steric shielding effect. The hemisulfate group in the polysulfabetaines, however, was found to be partially labile.
Synthetic routes to a collection of new fluorescent dyes are described, which are based on the [1,3]-dioxolo[4.5-f]benzodioxole (DBD) core. By introducing different electron withdrawing groups in 4- and 8-position of the DBD moiety the emission wavelength could be adjusted over a large spectral range from blue to orange light.
Crosslinking of thermoplastics is a versatile method to create crystallizable polymer networks, which are of high interest for shape-memory actuators. Here, crosslinked poly(epsilon-caprolactone) thermosets (cPCLs) were prepared from linear starting material, whereby the amount of extractable polymer was varied. Fractions of 5-60 wt % of non-crosslinked polymer chains, which freely interpenetrate the crosslinked network, were achieved leading to differences in the resulting phase of the bulk material. This can be described as "sponge-like" with open or closed compartments depending on the amount of interpenetrating polymer. The crosslinking density and the average network chain length remained in a similar range for all network structures, while the theoretical accessible volume for reptation of the free polymer content is affected. This feature could influence or introduce new functions into the material created by thermomechanical treatment. The effect of interpenetrating PCL in cPCLs on the reversible actuation was analyzed by cyclic, uniaxial tensile tests. Here, high reversible strains of up to Delta epsilon = 24% showed the enhanced actuation performance of networks with a non-crosslinked PCL content of 30 wt % resulting from the crystal formation in the phase of the non-crosslinked PCL and co-crystallization with network structures. Additional functionalities are reprogrammability and self-healing capabilities for networks with high contents of extractable polymer enabling reusability and providing durable actuator materials.
Fabrication of well-ordered porous silicon tubular structures using colloidal lithography and metal assisted chemical etching is reported. A continuous hexagonal hole/particle gold pattern was designed over monocrystalline silicon through deposition of polyNIPAM microspheres, followed by the surface decoration with gold nanoparticles and thermal treatment. An etching reaction with HF, ethanol and H2O2 dissolved the silicon in contact with the metal nanoparticles (NP), creating a porous tubular array in the "off-metal area". The morphological characterization revealed the formation of a cylindrical hollow porous tubular shape with external and internal diameter of approx. 900 nm and 400 nm respectively, though it can be tuned to other desired sizes by choosing an appropriate dimension for the microspheres. The porous morphology and optical properties were studied as a function of resistivity of silicon substrates. Compared to two different gold templates on cSi and nontubular porous pillar structures, porous silicon tubular framework revealed a maximum surface enhanced Raman scattering enhancement factor of 10(6) for the detection of 6-mercaptopurine (6-MP). Due to the large surface area available for any surface modification, open nanostructured platforms such as those studied here have potential applications in the field of reflection/photoluminescene and SERS based optical bio-/chemical sensors.
Silk protein-based materials show promise for application as biomaterials for tissue engineering. The simple and rapid photochemical modification of silk protein-based materials composed of either Bombyx mori silkworm silk or engineered spider silk proteins (eADF4(C16)) is reported. Radicals formed on the silk-based materials initiate the polymerization of monomers (acrylic acid, methacrylic acid, or allylamine) which functionalize the surface of the silk materials with poly(acrylic acid) (PAA), poly(methacrylic acid) (PMAA), or poly(allylamine) (PAAm). To demonstrate potential applications of this type of modification, the polymer-modified silks are mineralized. The PAA- and PMAA-functionalized silks are mineralized with calcium carbonate, whereas the PAAm-functionalized silks are mineralized with silica, both of which provide a coating on the materials that may be useful for bone tissue engineering, which will be the subject of future investigations.
Femtosecond-Pulsed laser written and etched fiber bragg gratings for fiber-optical biosensing
(2018)
We present the development of a label-free, highly sensitive fiber-optical biosensor for online detection and quantification of biomolecules. Here, the advantages of etched fiber Bragg gratings (eFBG) were used, since they induce a narrowband Bragg wavelength peak in the reflection operation mode. The gratings were fabricated point-by-point via a nonlinear absorption process of a highly focused femtosecond-pulsed laser, without the need of prior coating removal or specific fiber doping. The sensitivity of the Bragg wavelength peak to the surrounding refractive index (SRI), as needed for biochemical sensing, was realized by fiber cladding removal using hydrofluoric acid etching. For evaluation of biosensing capabilities, eFBG fibers were biofunctionalized with a single-stranded DNA aptamer specific for binding the C-reactive protein (CRP). Thus, the CRP-sensitive eFBG fiber-optical biosensor showed a very low limit of detection of 0.82 pg/L, with a dynamic range of CRP detection from approximately 0.8 pg/L to 1.2 mu g/L. The biosensor showed a high specificity to CRP even in the presence of interfering substances. These results suggest that the proposed biosensor is capable for quantification of CRP from trace amounts of clinical samples. In addition, the adaption of this eFBG fiber-optical biosensor for detection of other relevant analytes can be easily realized.
Femtosecond-pulsed laser written and etched fiber bragg gratings for fiber-optical biosensing
(2018)
We present the development of a label-free, highly sensitive fiber-optical biosensor for online detection and quantification of biomolecules. Here, the advantages of etched fiber Bragg gratings (eFBG) were used, since they induce a narrowband Bragg wavelength peak in the reflection operation mode. The gratings were fabricated point-by-point via a nonlinear absorption process of a highly focused femtosecond-pulsed laser, without the need of prior coating removal or specific fiber doping. The sensitivity of the Bragg wavelength peak to the surrounding refractive index (SRI), as needed for biochemical sensing, was realized by fiber cladding removal using hydrofluoric acid etching. For evaluation of biosensing capabilities, eFBG fibers were biofunctionalized with a single-stranded DNA aptamer specific for binding the C-reactive protein (CRP). Thus, the CRP-sensitive eFBG fiber-optical biosensor showed a very low limit of detection of 0.82 pg/L, with a dynamic range of CRP detection from approximately 0.8 pg/L to 1.2 µg/L. The biosensor showed a high specificity to CRP even in the presence of interfering substances. These results suggest that the proposed biosensor is capable for quantification of CRP from trace amounts of clinical samples. In addition, the adaption of this eFBG fiber-optical biosensor for detection of other relevant analytes can be easily realized.
Background/Aims: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32:1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM. (c) 2018 The Author(s) Published by S. Karger AG, Basel
A straightforward approach for the precise multifunctional surface modification of particles with three-dimensional patches using microcontact printing is presented. By comparison to previous works it was possible to not only control the diameter, but also to finely tune the thickness of the deposited layer, opening up the way for three-dimensional structures and orthogonal multifunctionality. The use of PEI as polymeric ink, PDMS stamps for microcontact printing on silica particles and the influence of different solvents during particle release on the creation of functional particles with three-dimensional patches are described. Finally, by introducing fluorescent properties by incorporation of quantum dots into patches and by particle self-assembly via avidin-biotin coupling, the versatility of this novel modification method is demonstrated.
This study aims to develop a rapid, sensitive and cost-effective biomimetic electrochemical sensor for artemisinin determination in plant extracts and for pharmacokinetic studies. A novel molecularly imprinted polymer (MIP)based electrochemical sensor was developed by electropolymerization of o-phenylenediamine (o-PD) in the presence of artemisinin on gold wire surface for sensitive detection of artemisinin. The experimental parameters, including selection of functional monomer, polymerization conditions, template extraction after polymerization, influence of pH and buffer were all optimized. Every step of imprinted film synthesis were evaluated by employing voltammetry techniques, surface-enhanced infrared absorption spectroscopy (SEIRAS) and atomic force microscopy (AFM). The specificity was further evaluated by investigating non-specific artemisinin binding on non-imprinted polymer (NIP) surfaces and an imprinting factor of 6.8 was achieved. The artemisinin imprinted polymers using o-PD as functional monomer have provided highly stable and effective binding cavities for artemisinin. Cross-reactivity studies with drug molecules showed that the MIPs are highly specific for artemisinin. The influence of matrix effect was further investigated both in artificial plant matrix and diluted human serum. The results revealed a high affinity of artemisinin-MIP with dissociation constant of 7.3 x 10(-9) M and with a detection limit of 0.01 mu M and 0.02 mu M in buffer and plant matrix, respectively.
Due to a challenging population growth and environmental changes, a need for new routes to provide required chemicals for human necessities arises. An effective solution discussed in this thesis is industrial heterogeneous catalysis. The development of an advanced industrial heterogeneous catalyst is investigated herein by considering porous carbon nano-material as supports and modifying their surface chemistry structure with heteroatoms. Such modifications showed a significant influence on the performance of the catalyst and provided a deeper insight regarding the interaction between the surface structure of the catalyst and the surrounding phase. This thesis contributes to the few present studies about heteroatoms effect on the catalyst performance and emphasizes on the importance of understanding surface structure functionalization in a catalyst in different phases (liquid and gaseous) and for different reactions (hydrogenolysis, oxidation, and hydrogenation/ polymerization). Herein, the heteroatoms utilized for the modifications are hydrogen (H), oxygen (O), and nitrogen (N). The heteroatoms effect on the metal particle size, on the polarity of the support/ the catalyst, on the catalytic performance (activity, selectivity, and stability), and on the interaction with the surrounding phase has been explored. First hierarchical porous carbon nanomaterials functionalized with heteroatoms (N) is synthesized and applied as supports for nickel nanoparticles for hydrogenolysis process of kraft lignin in liquid phase. This reaction has been performed in batch and flow reactors for three different catalysts, two of comparable hierarchical porosity, yet one is modified with N and the other is not, and a third is a prepared catalyst from a commercial carbon support. The reaction production and analyses show that the catalysts with hierarchical porosity perform catalytically much better than in presence of a commercial carbon support with lower surface area. Moreover, the modification with N-heteroatoms enhanced the catalytic performance because the heteroatom modified porous carbon material with nickel nanoparticles catalyst (Ni-NDC) performed highest among the other catalysts. In the flow reactor, Ni-NDC selectively degraded the ether bonds (β-O-4) in kraft lignin with an activity of 2.2 x10^-4 mg lignin mg Ni-1 s-1 for 50 h at 350°C and 3.5 mL min-1 flow, providing ~99 % conversion to shorter chained chemicals (mainly guaiacol derivatives). Then, the functionalization of carbon surface was further studied in selective oxidation of glucose to gluconic acid using < 1 wt. % of gold (Au) deposited on the previously-mentioned synthesized carbon (C) supports with different functionalities (Au-CGlucose, Au-CGlucose-H, Au-CGlucose-O, Au-CGlucoseamine). Except for Au-CGlucose-O, the other catalysts achieved full glucose conversion within 40-120 min and 100% selectivity towards gluconic acid with a maximum activity of 1.5 molGlucose molAu-1 s-1 in an aqueous phase at 45 °C and pH 9. Each heteroatom influenced the polarity of the carbon differently, affecting by that the deposition of Au on the support and thus the activity of the catalyst and its selectivity. The heteroatom effect was further investigated in a gas phase. The Fischer-Tropsch reaction was applied to convert synthetic gas (CO and H2) to short olefins and paraffins using surface-functionalized carbon nanotubes (CNTs) with heteroatoms as supports for ion (Fe) deposition in presence and absence of promoters (Na and S). The results showed the promoted Fe-CNT doped with nitrogen catalyst to be stable up to 180 h and selective to the formation of olefins (~ 47 %) and paraffins (~6 %) with a conversion of CO ~ 92 % at a maximum activity of 94 *10^-5 mol CO g Fe-1 s-1. The more information given regarding this topic can open wide range of applications not only in catalysis, but in other approaches as well. In conclusion, incorporation of heteroatoms can be the next approach for an advanced industrial heterogeneous catalyst, but also for other applications (e.g. electrocatalysis, gas adsorption, or supercapacitors).
Die vorliegende Arbeit behandelt die Synthese und Charakterisierung von funktionalisierten Alkydharzen und die photoinduzierte Polymerisation dieser unter Einsatz einer Quecksilberdampflampe oder einer UV LED mit unterschiedlicher Lichtintensität. Der Fokus dieser Arbeit bestand in der gezielten Substitution der internalen Doppelbindungen der Fettsäureester durch reaktivere Gruppen, wie Acrylate oder Methacrylate, welche für Alkydharze in dieser Form so in der Literatur nicht beschrieben sind. Untersuchungen des Polymerisationsverhaltens dieser funktionalisierten Harze wurden mit der Photo DSC durchgeführt, wobei Bis – (4 – methoxybenzoyl) diethylgermanium als Photoinitiator diente. Die Ergebnisse haben gezeigt, dass die Harze radikalisch polymerisiert werden können und eine geringere Abhängigkeit von der Umgebungsatmosphäre (Luftsauerstoff bzw. Stickstoff) vorliegt. Dies ist so in der Literatur für funktionalisierte Alkydharze nicht bekannt. Abmischungen von unterschiedlichen Monomeren und funktionalisierten Harzen bewirkten eine Steigerung der Viskosität sowie eine Verringerung der Sauerstoffinhibierung im Zuge der photoinduzierten Polymerisation unter Luftsauerstoff für die Quecksilberdampflampe und der UV LED.
Zur Untersuchung der sauerstoffinhibierenden Wirkung der Harze sind Synthesen unterschiedlicher, funktionalisierter Ölsäuremethylester als Modellsubstanzen durchgeführt worden. Ein verbessertes Polymerisationsverhalten und eine geringe Abhängigkeit von der Umgebungsatmosphäre konnte für die Modelle nachgewiesen werden. Zur Aufklärung des verbesserten Polymerisationsverhaltens sind gezielt Substituenten (Imidazol, Brom, Alkohol, Acetat) in den funktionalisierten Ölsäuremethylester eingebaut worden, um den Einfluss dieser aufzuzeigen. Im Rahmen dieser Synthesen sind neuartige Strukturen synthetisiert worden, welche so in der Literatur nicht beschrieben sind. Die Gegenüberstellung der Polymerisationszeit, der Umsatz der (Meth-)Acrylatgruppen sowie die Zeit zum Erreichen der maximalen Polymerisationsgeschwindigkeit unter Verwendung von unterschiedlichen UV Lichtquellen hat einen Einfluss der Substituenten auf das Polymerisationsverhalten gezeigt.
Generation of 3-dimensional multi-patches on silica particles via printing with wrinkled stamps
(2018)
A simple route towards patchy particles with anisotropic patches with respect to a different functionality and directionality is presented. This method is based on microcontact printing of positively charged polyethylenimine (PEI) on silica particles using wrinkled stamps. Due to the wrinkled surface, the number of patches on the particles as well as the distance between two patches can be controlled.
In der vorliegenden Arbeit werden Wege zur Gewinnung verschiedener phenolischer Substanzen wie Lignin, Diarylheptanoide und 4-(3-Oxobutyl)phenol (Himbeerketon) aus dem Stamm der Hängebirke (Betula pendula) aufgezeigt. Durch Methacrylierung des 4-(3-Oxobutyl)phenols wurde ein Monomer erzeugt, welches mittels freier radikalischer Masse- und Lösungspolymerisation, sowie enzymatischer Polymerisation polymerisiert werden kann.
Eine erste Isolierung von Bestandteilen wurde durch Extraktion von Innenholz bzw. Rinde mit Methanol erzielt. Die in Methanol unlöslichen Bestandteile des Innenholzes und der Rinde wurden anschließend mit ausgewählten ionischen Flüssigkeiten extrahiert. Es wurde ein Verfahren zum selektiven Trennen der mit diesen ionischen Flüssigkeiten extrahierten Bestandteile in Cellulose, Hemicellulose, Lignin und mit Ethylacetat extrahierbare Bestandteile entwickelt. Hierdurch war es möglich, sowohl die verwendeten ionischen Flüssigkeiten als auch das Innenholz und die Rinde hinsichtlich ihres Extraktionsverhaltens miteinander zu vergleichen.
Ferner wurden verschiedene Strategien aufgezeigt, um insgesamt drei Spezies an Diarylheptanoiden aus dem methanolischen Extrakt der Rinde zu isolieren. Eines der gefundenen Diarylheptanoide (5 Hydroxy-1,7-bis(4-hydroxyphenyl)-3-heptanon) wurde via Retroaldolreaktion in 4 (3 Oxobutyl)phenol (Himbeerketon) und 3 (4 Hydroxyphenyl)propanal gespalten.
Es wurde die Verwendung des 4-(3-Oxobutyl)phenol als Monomerbestandteil untersucht. Hierfür wurde 4-(3-Oxobutyl)phenylmethacrylat synthetisiert und Wege zur Reinigung mittels Säulenchromatographie und Umkristallisation aufgezeigt. Anschließend wurde Poly(4-(3-oxobutyl)phenylmethacrylat) (PObMA) und Polybenzylmethacrylats (PBzMA) aus Massen- und Lösungspolymerisation hergestellt. Die Ausbeuten an PObpMA im Vergleich zum PBzMA liegen bei gleichen Reaktionsbedingungen auf gleichem Niveau. Im Kontrast hierzu ist der Polymerisationsgrad aus freier radikalischer Polymerisation in Masse des PObpMA im Vergleich zum PBzMA um den Faktor 3,7 größer. Die Glasübergangstemperaturen des PObpMA liegen bei gleichen Reaktionsbedingungen sowohl bei freier radikalischer Polymerisation in Masse, als auch bei Lösungspolymerisation über denen des PBzMA. Darüber hinaus wurde die Polymerisation von 4-(3-Oxobutyl)phenylmethacrylat und Benzylmethacrylat mit einem Initiatorsystem bestehend aus Meerrettichperoxidase, Acetylaceton und Wasserstoffperoxid bei Raumtemperatur beschrieben. Die mit enzymatischem Initiatorsystem erzeugten Produkte zeigten starke Übereinstimmung mit Produkten aus Lösungspolymerisationen, welche mit Azobis(isobutyronitril) initiiert wurden.
Helical chirality is a novel enantioselectivity-inducing property in transition-metal-catalyzed transformations. The principle is illustrated herein for the example of asymmetric olefin metathesis. This work reports the synthesis of the first helically chiral Ru-NHC alkylidene complex from an aminohelicene-derived imidazolium salt, which was ligated to the first generation Hoveyda-Grubbs catalyst. Kinetic data were acquired for benchmark test reactions and compared to an achiral catalyst. The helically chiral Ru-catalyst was evaluated in asymmetric ring-closing metathesis (RCM) and ring-opening metathesis-cross-metathesis (ROM/CM) reactions, which proceeded with promising levels of enantioselectivity. Extensive NMR-spectroscopic investigations and a DFT geometry optimization were performed. These results led to a topographic steric map and calculation of percent-buried-volume values for each quadrant around the metal center.
We present the fabrication of TiO2 nanotube electrodes with high biocompatibility and extraordinary spectroscopic properties. Intense surface-enhanced resonance Raman signals of the heme unit of the redox enzyme Cytochromeb(5) were observed upon covalent immobilization of the protein matrix on the TiO2 surface, revealing overall preserved structural integrity and redox behavior. The enhancement factor could be rationally controlled by varying the electrode annealing temperature, reaching a record maximum value of over 70 at 475 degrees C. For the first time, such high values are reported for non-directly surface-interacting probes, for which the involvement of charge-transfer processes in signal amplification can be excluded. The origin of the surface enhancement is exclusively attributed to enhanced localized electric fields resulting from the specific optical properties of the nanotubular geometry of the electrode.
Whereas the reversible reduction of azobenzenes has been known for decades, their oxidation is destructive and as a result has been notoriously overlooked. Here, we show that a chain reaction leading to quantitative Z -> E isomerization can be initiated before reaching the destructive anodic peak potential. This hole-catalyzed pathway is accessible to all azobenzenes, without exception, and offers tremendous advantages over the recently reported reductive, radical-anionic pathway because it allows for convenient chemical initiation without the need for electrochemical setups and in the presence of air. In addition, catalytic amounts of metal-free sensitizers, such as methylene blue, can be used as excited-state electron acceptors, enabling a shift of the excitation wavelength to the far red of the azobenzene absorption (up to 660 nm) and providing quantum yields exceeding unity (up to 200%). Our approach will boost the efficiency and sensitivity of optically dense liquid-crystalline and solid photo-switchable materials.
Perovskite solar cells (PSCs) are currently one of the most promising photovoltaic technologies for highly efficient and cost-effective solar energy production. In only a few years, an unprecedented progression of preparation procedures and material compositions delivered lab-scale devices that have now reached record power conversion efficiencies (PCEs) higher than 20%, competing with most established solar cell materials such as silicon, CIGS, and CdTe. However, despite a large number of researchers currently involved in this topic, only a few groups in the world can reproduce >20% efficiencies on a regular n-i-p architecture. In this work, we present detailed protocols for preparing PSCs in regular (n-i-p) and inverted (p-i-n) architectures with >= 20% PCE. We aim to provide a comprehensive, reproducible description of our device fabrication , protocols. We encourage the practice of reporting detailed and transparent protocols that can be more easily reproduced by other laboratories. A better reporting standard may, in turn, accelerate the development of perovskite solar cells and related research fields.
2-Amino-2-(hydroxymethyl)-1,3-propanediol (TRIS) and ethylenediaminetetraacetic acid ( EDTA) are key components of biological buffers and are frequently used as DNA stabilizers in irradiation studies. Such surface or liquid phase studies are done with the aim to understand the fundamental mechanisms of DNA radiation damage and to improve cancer radiotherapy. When ionizing radiation is used, abundant secondary electrons are formed during the irradiation process, which are able to attach to the molecular compounds present on the surface. In the present study we experimentally investigate low energy electron attachment to TRIS and methyliminodiacetic acid ( MIDA), an analogue of EDTA, supported by quantum chemical calculations. The most prominent dissociation channel for TRIS is through hydroperoxyl radical formation, whereas the dissociation of MIDA results in the formation of formic and acetic acid. These compounds are well-known to cause DNA modifications, like strand breaks. The present results indicate that buffer compounds may not have an exclusive protecting effect on DNA as suggested previously.
In this study, the apparent relationship between the transport process and the surface chemistry of the Calcium-Silicate Hydrate (CSH) phases was investigated. For this purpose, a method was developed to synthesize ultrathin CSH phases to be used as a model substrate with the specific modification of their structure by introducing europium (Eu(III)). The structural and chemical changes during this Eu(III)-doping were observed by means of infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS), and time-resolved laser fluorescence spectroscopy (TRLFS). These alterations of the CSH phases led to significant changes in the surface chemistry and consequently to considerable variations in the interaction with water, as evidenced by measurements of the contact angles on the modified model substrates. Our results provide the basis for a more profound molecular understanding of reactive transport processes in cement-based systems. Furthermore, these results broaden the perspective of improving the stability of cement-based materials, which are subjected to the impact of aggressive aqueous environments through targeted modifications of the CSH phases.
Polypeptoids are noticeable biological materials due to their versatile properties and various applications in drug delivery, surface modification, self-assembly, etc. N-Substituted glycine N-thiocarboxyanhydrides (NNTAs) are more stable monomers than the corresponding N-carboxyanhydrides (NNCAs) and enable one to prepare polypeptoids via ring-opening polymerization even in the presence of water. However, larger amounts of water (>10,000 ppm) cause inhibition of the polymerization. Herein, we discover that during polymerization hydrogen sulfide evolves from the hydrolysis of carbonyl sulfide, which is the byproduct of ring-opening reaction, and reacts with NNTA to produce cyclic oligopeptoids. The capture of N-ethylethanethioic acid as an intermediate product confirms the reaction mechanism together with density functional theory quantum computational results. By bubbling the polymerization solution with argon, the side reaction can be suppressed to allow the synthesis of polysarcosine with high molar mass (M-n = 11,200 g/mol, D = 1.25) even in the presence of similar to 10,000 ppm of water.
The implementation of shape-memory effects (SME) in polymeric micro- or nano-objects currently relies on the application of indirect macroscopic manipulation techniques, for example, stretchable molds or phantoms, to ensembles of small objects. Here, we introduce a method capable of the controlled manipulation and SME quantification of individual micro- and nano-objects in analogy to macroscopic thermomechanical test procedures. An atomic force microscope was utilized to address individual electro-spun poly(ether urethane) (PEU) micro- or nanowires freely suspended between two micropillars on a micro-structured silicon substrate. In this way, programming strains of 10 +/- 1% or 21 +/- 1% were realized, which could be successfully fixed. An almost complete restoration of the original free-suspended shape during heating confirmed the excellent shape-memory performance of the PEU wires. Apparent recovery stresses of sigma(max,app)=1.2 +/- 0.1 and 33.3 +/- 0.1MPa were obtained for a single microwire and nanowire, respectively. The universal AFM test platform described here enables the implementation and quantification of a thermomechanically induced function for individual polymeric micro- and nanosystems.
BACKGROUND: Physical and chemical characteristics of implant materials determine the fate of long-term cardiovascular devices. However, there is still a lack of fundamental understanding of the molecular mechanisms occurring in the material-tissue interphase. In a previous study, soft covalently crosslinked poly(n-butyl acrylate) networks (cPnBA) were introduced as sterilizable, non-toxic and immuno-compatible biomaterials with mechanical properties adjustable to blood vessels. Here we study the influence of different surface treatments in particular oxygen plasma modification and fibrinogen deposition as well as a combinatorial approach on the adhesion and viability of fibroblasts. RESULTS: Compared to non-treated cPnBAs the advancing water-contact angles were found to be reduced after all surface modifications (p<0.05, each), while lowest values were observed after the combined surface treatment (OPT+FIB). The latter differed significantly from the single OPT and FIB. The number of adherent fibroblasts and their adherence behavior differed on both pristine cPnBA networks. The fibroblast density on cPnBA04 was 743 +/- 434 cells. mm(-2), was about 6.5 times higher than on cPnBA73 with 115 +/- 73 cells. mm(-2). On cPnBA04 about 20% of the cells were visible as very small, round and buckled cells while all other cells were in a migrating status. On cPnBA73, nearly 50% of fibroblasts were visible as very small, round and buckled cells. The surface functionalization either using oxygen plasma treatment or fibrinogen coating led to a significant increase of adherent fibroblasts, particularly the combination of both techniques, for both cPnBA networks. It is noteworthy to mention that the fibrinogen coating overruled the characteristics of the pristine surfaces; here, the fibroblast densities after seeding were identical for both cPnBAnetworks. Thus, the binding rather depended on the fibrinogen coating than on the substrate characteristics anymore. While the integrity of the fibroblasts membrane was comparable for both polymers, the MTS tests showed a decreased metabolic activity of the fibroblasts on cPnBA. CONCLUSION: The applied surface treatments of cPnBA successfully improved the adhesion of viable fibroblasts. Under resting conditions as well as after shearing the highest fibroblast densities were found on surfaces with combined post-treatment.
Most investigations on phase inversion (PI) of resins upon addition of water have been carried out by dynamic light scattering (DLS), torque, and viscosity measurements. The main problem, however, is analytic discontinuity due to sample removal and a changing matrix due to dilution during the preparation of the aqueous resin dispersions. This work presents Photon Density Wave (PDW) spectroscopy as a tool for the inline characterization of the acetone process for an acrylic copolymer with high acrylic acid (AA) content. PDW spectroscopy revealed different trends for optical properties compared to torque during water feed. Also the absence of PI due to dissolution of copolymer in the solvent/water mixture is observed by PDW spectroscopy. PI for the investigated copolymer did not occour during water feed but during removal of solvent. Different feeding rates of water gave similar trends while a change in temperature and degree of AA neutralization led to changes in optical properties and torque. Thermal processing showed that the optical properties of mixtures prior and after removal of solvent were completely different caused by changes of solubility.
Efficiencies >20% are obtained from the perovskite solar cells (PSCs) employing Cs+ and Rb+ based perovskite compositions; therefore, it is important to understand the effect of these inorganic cations specifically Rb+ on the properties of perovskite structures. Here the influence of Cs+ and Rb+ is elucidated on the structural, morphological, and photophysical properties of perovskite structures and the photovoltaic performances of resulting PSCs. Structural, photoluminescence (PL), and external quantum efficiency studies establish the incorporation of Cs+ (x < 10%) but amply rule out the possibility of Rb-incorporation into the MAPbI(3) (MA = CH3NH3+) lattice. Moreover, morphological studies and time-resolved PL show that both Cs+ and Rb+ detrimentally affect the surface coverage of MAPbI(3) layers and charge-carrier dynamics, respectively, by influencing nucleation density and by inducing nonradiative recombination. In addition, differential scanning calorimetry shows that the transition from orthorhombic to tetragonal phase occurring around 160 K requires more thermal energy for the Cs-containing MAPbI(3) systems compared to the pristine MAPbI(3). Investigation including mixed halide (I/Br) and mixed cation A-cation based compositions further confirms the absence of Rb+ from the 3D-perovskite lattice. The fundamental insights gained through this work will be of great significance to further understand highly promising perovskite compositions.
We discuss recent investigations of the interaction of polyelectrolytes with proteins. In particular, we review our recent studies on the interaction of simple proteins such as human serum albumin (HSA) and lysozyme with linear polyelectrolytes, charged dendrimers, charged networks, and polyelectrolyte brushes. In all cases discussed here, we combined experimental work with molecular dynamics (MD) simulations and mean-field theories. In particular, isothermal titration calorimetry (ITC) has been employed to obtain the respective binding constants K-b and the Gibbs free energy of binding. MD simulations with explicit counterions but implicit water demonstrate that counterion release is the main driving force for the binding of proteins to strongly charged polyelectrolytes: patches of positive charges located on the surface of the protein become multivalent counterions of the polyelectrolyte, thereby releasing a number of counterions condensed on the polyelectrolyte. The binding Gibbs free energy due to counterion release is predicted to scale with the logarithm of the salt concentration in the system, which is verified by both simulations and experiment. In several cases, namely, for the interaction of proteins with linear polyelectrolytes and highly charged hydrophilic dendrimers, the binding constant could be calculated from simulations to very good approximation. This finding demonstrated that in these cases explicit hydration effects do not contribute to the Gibbs free energy of binding. The Gibbs free energy can also be used to predict the kinetics of protein uptake by microgels for a given system by applying dynamic density functional theory. The entire discussion demonstrates that the direct comparison of theory with experiments can lead to a full understanding of the interaction of proteins with charged polymers. Possible implications for applications, such as drug design, are discussed.
The limited capacity of cartilage to heal large lesions through endogenous mechanisms has led to extensive effort to develop materials to facilitate chondrogenesis. Although physical-chemical properties of biomaterials have been shown to impact in vitro chondrogenesis, whether these findings are translatable in vivo is subject of debate. Herein, architectured 3D hydrogel scaffolds (ArcGel) (produced by crosslinking gelatin with ethyl lysine diisocyanate (LDI)) were used as a model system to investigate the interplay between scaffold mechanical properties and degradation on matrix deposition by human articular chondrocytes (HAC) from healthy donors in vitro and in vivo. Using ArcGel scaffolds of different tensile and shear modulus, and degradation behavior; in this study, we compared the fate of ex vivo engineeredArcGels-chondrocytes constructs, i.e. the traditional tissue engineering approach, with the de novo formation of cartilaginous tissue in HAC laden ArcGels in an ectopic nude mouse model. While the softer and fast degrading ArcGel (LNCO3) was more efficient at promoting chondrogenic differentiation in vitro, upon ectopic implantation, the stiffer and slow degrading ArcGel (LNCO8) was superior in maintaining chondrogenic phenotype in HAC and retention of cartilaginous matrix. Furthermore, surprisingly the de novo formation of cartilage tissue was promoted only in LNCO8. Since HAC cultured for only three days in the LNCO8 environment showed upregulation of hypoxia-associated genes, this suggests a potential role for hypoxia in the observed in vivo outcomes. In summary, this study sheds light on how immediate environment (in vivo versus in vitro) can significantly impact the outcomes of cell-laden biomaterials. Statement of Significance In this study, 3D architectured hydrogels (ArcGels) with different mechanical and biodegradation properties were investigated for their potential to promote formation of cartilaginous matrix by human articular chondrocytes in vitro and in vivo. Two paradigms were explored (i) ex vivo engineering followed by in vivo implantation in ectopic site of nude mice and (ii) short in vitro culture (3 days) followed by implantation to induce de novo cartilage formation. Softer and fast degrading ArcGel were better at promoting chondrogenesis in vitro, while stiffer and slow degrading ArcGel were strikingly superior in both maintaining chondrogenesis in vivo and inducing de novo formation of cartilage. Our findings highlight the importance of the interplay between scaffold mechanics and degradation in chondrogenesis.
Hepcidin-25 was identified as themain iron regulator in the human body, and it by binds to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II) binding site known as the ATCUN (amino-terminal Cu(II)- and Ni(II)-binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the complex formed between hepcidin-25 and copper could reveal insight into its biological role. The present work focuses on metal-bound hepcidin-25 that can be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25 achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandemmass spectrometry (MS/MS), high-resolutionmass spectrometry (HRMS)) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a three-dimensional (3D)model of hepcidin-25with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or referencematerial comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others.
Health effects, attributed to the environmental pollution resulted from using solvents such as benzene, are relatively unexplored among petroleum workers, personal use, and laboratory researchers. Solvents can cause various health problems, such as neurotoxicity, immunotoxicity, and carcinogenicity. As such it can be absorbed via epidermal or respiratory into the human body resulting in interacting with molecules that are responsible for biochemical and physiological processes of the brain.
Owing to the ever-growing demand for finding a solution, an Ionic liquid can use as an alternative solvent. Ionic liquids are salts in a liquid state at low temperature (below 100 C), or even at room temperature. Ionic liquids impart a unique architectural platform, which has been interesting because of their unusual properties that can be tuned by simple ways such as mixing two ionic liquids.
Ionic liquids not only used as reaction solvents but they became a key developing for novel applications based on their thermal stability, electric conductivity with very low vapor pressure in contrast to the conventional solvents.
In this study, ionic liquids were used as a solvent and reactant at the same time for the novel nanomaterials synthesis for different applications including solar cells, gas sensors, and water splitting.
The field of ionic liquids continues to grow, and become one of the most important branches of science. It appears to be at a point where research and industry can work together in a new way of thinking for green chemistry and sustainable production.
New mesoporous silk fibroin (SF)/silica hybrids were processed via a one-pot soft and energy-efficient sol-gel chemistry and self-assembly from a silica precursor, an acidic or basic catalyst, and the ionic liquid 1-butyl-3-methylimidazolium chloride, acting as both solvent and mesoporosity-inducer. The as-prepared materials were obtained as slightly transparent-opaque, amorphous monoliths, easily transformed into powders, and stable up to ca. 300 degrees C. Structural data suggest the formation of a hexagonal mesostructure with low range order and apparent surface areas, pore volumes, and pore radii of 205-263 m(2) g(-1), 0.16-0.19 cm(3) g(-1), and 1.2-1.6 nm, respectively. In all samples, the dominating conformation of the SF chains is the beta-sheet. Cytotoxicity/bioactivity resazurin assays and fluorescence microscopy demonstrate the high viability of MC3T3 pre-osteoblasts to indirect (>= 99 +/- 9%) and direct (78 +/- 2 to 99 +/- 13%) contact with the SF/silica materials. Considering their properties and further improvements, these systems are promising candidates to be explored in bone tissue engineering. They also offer excellent prospects as electrolytes for solid-state electrochemical devices, in particular for fuel cells.