Development and chromatographic exploration of stable-bonded cross-linked amino silica against classical amino phases.

The present work reports on a novel stable-bonded amino silica stationary phase obtained by crosslinking of surface aminopropyl moieties using triglycidyl isocyanurate. The obtained cross-linked amido-amino network silica material exhibited superior hydrolytic stability compared to classical 3-aminopropyl phases and showed, inter alia, excellent separation of nine therapeutically effective sulfonamides in hydrophilic interaction/weak anion exchange chromatography elution mode. Additionally, the separation of carbohydrates was investigated under classical hydrophilic interaction chromatography conditions as well proving the suitability of the novel phase for such applications. For the evaluation of the hydrolytic stability the prepared material, as well as two commercially available benchmark columns and a set of in-house synthesized amino-modified materials, were exposed to harsh aqueous mobile phase conditions for in total of 50 h at elevated temperature. In this context, the materials were examined by elemental analysis, (13 C and 29 Si cross-polarization/magic angle spinning) solid-state nuclear magnetic resonance, and a chromatographic test before and subsequent to the exposure to these stress conditions. Lastly, the new stationary phase was classified in comparison to a set of commercially available stationary phases by principal component analysis of resultant retention factors gained from chromatographic standard tests.

Comprehensive profiling of conjugated fatty acid isomers and their lipid oxidation products by two-dimensional chiral RP×RP liquid chromatography hyphenated to UV- and SWATH-MS-detection.

This research reports on the development of a comprehensive two-dimensional liquid chromatography (2D-LC) method hyphenated to inline DAD-UV and ESI-QTOF-MS/MS-detection for the separation of conjugated polyunsaturated fatty acid isomers and structurally related (saturated, unconjugated, oxidized) compounds. In pharmaceutical lipid formulations conjugated fatty acids can be found as impurities, generated by oxidation of polyunsaturated fatty acids. Due to the structural complexity of resultant multi-component samples one dimensional liquid chromatography may be suboptimal for quality control and impurity profiling. The screened reversed-phase columns showed a lack of selectivity for the conjugated fatty acid isomers but the resolutions improved with the shape selectivity of the stationary phases (C18- < C30- < cholesteryl-ether-bonded). Further enhanced selectivity for the non-chiral conjugated FAs could be achieved with amylose/cellulose-based chiral stationary phases (CSPs) which harbor cavities for selective inclusion depending on E/Z configurations of the double bonds of the analytes. Amylose-based CSPs showed higher selectivity for conjugated fatty acids than the cellulose-based polysaccharide CSPs. Hyphenating the chiral and reversed-phase columns in a comprehensive 2D-LC-setup was favorable since they showed orthogonality and good compatibility, because both were operated under RP-conditions. The chiral dimension (1D) mainly separated the different isomers, while the reversed-phase dimension (2D) separated according to number of double bonds and degree of oxidation. Using this setup, advanced structural annotation of unknowns was possible based on UV-, MS1- and MS2-spectra. Data-independent acquisition (by SWATH) enabled differentiation of positional isomers of oxidized lipids by characteristic MS2-fragments and elucidation of co-eluted compounds by selective extracted ion chromatograms of fragment ions (MS2 EICs).

Controllable organosilane monolayer density of surface bonding using silatranes for thiol functionalization of silica particles for liquid chromatography and validation of microanalytical method for elemental composition determination.

The present work systematically investigates a new strategy for the functionalization of silica gel using alkyl silatrane chemistry instead of alkylsilanes for synthesis of chromatographic stationary phases. In this work, silica was chemically modified for further functionalization by a thiol-ene click reaction. Thus, 3-mercaptopropylsilatrane (MPS) was used which is capable to form self-assembled monolayers (SAM) on top of silanol surfaces in a controlled manner as previously shown for silicon wafers. The utility of this chemistry for stationary phase synthesis in liquid chromatography was not evaluated yet. Hence, silica surface modifications using MPS were studied in comparison to established 3-mercaptopropyltrimethoxysilane (MPTMS) chemistry. First, the employed elemental analysis method was validated and it showed excellent intra-day and inter-day precisions (typically less than 5% RSD). It could be shown that the reaction kinetics of MPS was roughly 35-times faster than with MPTMS. After 30 min reaction time with MPS, the thiol content reached 74% of the maximal coverage. Due to controlled chemistry with MPS, which does not lead to oligomeric siloxane network at the silica surface, the ligand coverage was lower. However, multiple silanization cycles with MPS led to a dense surface coverage (around 4 µmol m-2). 29Si cross polarization/magic angle spinning (CP/MAS) solid-state NMR revealed distinct T1/T2/T3 ratios for MPS and MPTMS materials with up to 80% T3 (indicative for trifunctional siloxane linkage) for MPS and around 20% T3 for MPTMS. This indicates a more homogeneous, thinner monolayer film of MPS on the silica surface, as compared to an irregular thick oligomeric siloxane network with MPTMS. Bonding of quinine carbamate as chiral selector afforded an efficient chiral stationary phase (CSP) for chromatographic enantiomer separation. Separation factors were comparable to MPTMS-bonded CSP, however, chromatographic efficiency was much better for the MPS-bonded CSP. H/u curves indicated a reduced mass transfer resistance by roughly factor 3 for MPS- compared to MPTMS-bonded CSP. This confirms better chromatographic performance of surfaces with homogeneous monolayer compared to network structures on the silica surface which suffer from poor stationary phase mass transfer.

Preparation and characterization of poly(3-mercaptopropyl)methylsiloxane functionalized silica particles and their further modification for silver ion chromatography and enantioselective high-performance liquid chromatography.

The present work reports on the preparation of polythiol-functionalized silica particles by thermally and photo-initiated radical addition reactions using poly(3-mercaptopropyl)methylsiloxane (PMPMS) as sulfhydryl group-rich surface modification reagent. Prior to surface modification with PMPMS, the silica was vinylized with vinyl trimethoxysilane. Finally, the usefulness of the thiolated silica particles was demonstrated by their further modification for various HPLC applications such as argentation chromatography and chiral separations. Aiming at a sulfhydryl group-rich, thin PMPMS layer on the surface of the silica several factors such as quantity of PMPMS, radical starter and reaction time were investigated by a design of experiment (DoE) approach. In thermally induced polymerization reactions 2,2'-azobis(isobutyronitrile) (AIBN) was used as radical starter, in photo-induced reactions 2,2-dimethoxy-2-phenylacetophenone (DMPA) was used instead. The incorporation of PMPMS was evaluated by elemental analysis and reactive and accessible sulfhydryl groups were determined by performing a thiol-disulfide exchange reaction with 2,2'-dipyridyl disulfide (DPDS). Consequently, thiol-functionalized silica particles (200 Å, 5 µm) with 1.81 ± 0.07 µmol sulfhydryl groups per m2 were prepared and further functionalized for silver ion chromatography and chiral separation chromatography clearly proving its utility as platform for further silica functionalization. The fabricated stationary phase for silver ion chromatography showed promising separation abilities for fatty acid methyl esters (FAME) according to the amount of double bonds within the fatty acid residue and cis- and trans-stilbene as model molecule for cis-trans isomerism. After the successful incorporation of O-tert-butylcarbamoyl quinine (tBuCQN) as chiral selector via thiol-ene click chemistry onto the PMPMS layer, the obtained chiral stationary phases (CSP) showed good separation of derivatized amino acids in polar organic elution mode comparable with a column based on commercially available CHIRALPAK QN-AX silica particles (120 Å, 5 µm).

[Which Industries Are Economically Relevant to the System?] / Welche Branchen sind ökonomisch systemrelevant?

With the economic shutdown in the wake of the COVID-19 pandemic, the importance of some industries for the national economy has come into focus. This report identifies industries that are closely linked with the rest of the economy through supply chains; stopping production in these industries would have a significant impact on the overall economy. On the one hand, there are industries in which production losses lead to massive demand losses in other industries. On the other hand, there are industries in which production downtimes lead to massive delivery difficulties for other industries. Beyond these interdependencies, we also account for negative effects stemming from the loss of income and from consumption or investment decisions.

Thiol-ene photo-click immobilization of a chiral chromatographic ligand on silica particles.

This work reports procedures for the immobilization of vinyl ligands on silica particles by UV-initiated thiol-ene radical addition reaction (photo-click immobilization). tert­Butylcarbamoyl quinine was the functional ligand (ene component) for the synthesis of chiral stationary phases. Two distinct surface chemistries were evaluated. In one approach, the ligand was directly attached to 3-mercaptopropyl-silica triggered by radicals generated by UV irradiation from a photoinitiator. In another approach, the ligand was immobilized onto vinyl silica via poly(3-mercaptopropyl-methylsiloxane) (PMPMS) as crosslinker by a photoinitiated double click reaction in which functionalization with chiral ligand and crosslinking to vinylsilica occurred simultaneously in one synthesis step. PMPMS-bonded CSPs were prepared from suspension (slurry method) or solventless after coating of the polythiol onto the vinylsilica surface (film method). Optimization by a design of experiment approach showed that the reaction time is the prime variable to optimize the surface coverage of chiral selector which also increased with PMPMS concentration. When the film formation of the latter approach was assisted by a minute volume of toluene during photo-click immobilization, selector coverage could be significantly increased to 0.73 µmol/m2 in a 2 h synthesis compared to 0.44 µmol/m2 by the solventless film method and 0.47 µmol/m2 by the slurry method under otherwise comparable conditions. The solvent assistance improved the chromatographic efficiency of the film method and resulted equal minimal reduced plate height of 2.6 as the slurry method for a chiral probe (Fmoc-Phe). The mass transfer resistance was around factor 2 smaller with the solvent-assisted film method as compared to the film approach without toluene, presumably due to a more homogenous distribution of the thin polymer film owing to lower dynamic viscosity in presence of toluene.

Fragment-based Design of Zwitterionic, Strong Cation- and Weak Anion-Exchange Type Mixed-mode Liquid Chromatography Ligands and their Chromatographic Exploration.

The role of individual functional groups has been assessed with regard to surface charge and chromatographic retention. Coatings were prepared from various fragments of the chiral zwitterionic materials Chiralpak ZWIX(+) and ZWIX(-). The different chromatographic ligands allowed fine tuning of the surface charge. Chiralpak ZWIX phases showed strongly negative ζ-potentials over the entire pH-range. Zwitterionic congeners with quinuclidine and sulfonic acid moieties but lacking the quinolone ring in the ligand structure exhibited shifted ζ-potentials of around + 5 to 20 mV depending on the surrounding residues. Capillary electrophoretic mobilitiy measurements with the chromatographic ligands and molecular dynamics simulations were carried out to offer some explanation of these surface charge differences of the distinct zwitterionic stationary phases. The new mixed-mode phases were also chromatographically characterized by simple RP and HILIC tests. The results allowed their positioning within a large variety of different commercially available RP, HILIC and mixed-mode phases, which were evaluated as well, by multivariate data processing using principal component analysis. The new mixed-mode phases overall exhibit reasonable hydrophilicity-lipophilicity balance and enable retention of ionic compounds by additional ionic interactions through weak anion-exchange (WAX-type), strong cation-exchange (SCX-type) or both (RP/ZWIX-type). Hence, the new RP/ZWIX phases can be flexible tools for selectivity tuning in RP and HILIC separations.

In-situ functionalized monolithic polysiloxane-polymethacrylate composite materials from polythiol-ene double click reaction in capillary column format for enantioselective nano-high-performance liquid chromatography.

This work reports on the proof-of-principle of preparation of novel one step in-situ functionalized monolithic polysiloxane-polymethacrylate composite materials in capillary columns for enantioselective nano-HPLC using a thiol-ene click reaction. Quinine carbamate as functional monomer and ethylene dimethacrylate as crosslinker were both used as ene components in a thermally initiated double click-type polymerization reaction with poly(3-mercaptopropyl)methylsiloxane as thiol component in presence of 1-propanol as porogenic solvent. Elemental analysis and on-capillary fluorescence measurement proved the successful incorporation of the functional chiral monomer into the polymer. Scanning electron microscopy images revealed a macroporous polymer morphology which is typical for a nucleation and growth mechanism of pore formation. The individual microglobules appear relatively spherical and smooth indicating a non-porous nature. Nano-HPLC experiments of the chiral monolithic capillary column provided successful enantiomer separation of N-3,5-dinitrobenzoylleucine as test compound in polar organic elution mode clearly documenting the successful implementation of the proposed concept towards new functionalized monolithic composite materials.

Sustainable energy development in Austria until 2020: Insights from applying the integrated model "e3.at"

This paper reports on the Austrian research project "Renewable energy in Austria: Modeling possible development trends until 2020". The project investigated possible economic and ecological effects of a substantially increased use of renewable energy sources in Austria. Together with stakeholders and experts, three different scenarios were defined, specifying possible development trends for renewable energy in Austria. The scenarios were simulated for the period 2006-2020, using the integrated environment-energy-economy model "e3.at". The modeling results indicate that increasing the share of renewable energy sources in total energy use is an important but insufficient step towards achieving a sustainable energy system in Austria. A substantial increase in energy efficiency and a reduction of residential energy consumption also form important cornerstones of a sustainable energy policy.

Horizontal and vertical pseudoneglect in peri- and extrapersonal space.

The present study investigates the influence of depth on pseudoneglect in healthy young participants (n=18) within three-dimensional virtual space, by presenting a variation of the greyscales task and a landmark task, which were specifically matched for stimulus-response compatibility, as well as perceptual factors within and across the tasks. Tasks were presented in different depth locations (peripersonal, extrapersonal) and different orientations (horizontal, vertical) within three-dimensional virtual space, using virtual reality technique. A horizontal leftward bias (pseudoneglect) for both tasks was found, which was stronger in peripersonal than in extrapersonal space. For the vertical condition, an upward bias was observed in the greyscales task, but not in the landmark task. These results support the hypotheses of right hemispheric dominance for visual spatial attention and our study is the first to examine horizontal and vertical orienting biases with the greyscales task in peri- and extrapersonal space. Furthermore, the differences in attentional asymmetries with respect to depth suggest dissociable neural mechanisms for visual attentional processing in near and far space and the lack of significant correlations implies independence of horizontal and vertical stimulus processing.

Evaluation of spatial processing in virtual reality using functional magnetic resonance imaging (FMRI).

While the ecological validity of virtual reality (VR) applications is usually assessed by behavioral data or interrogation, an alternative approach on a neuronal level is offered by brain imaging methods. Because it is yet unclear if 3D space in virtual environments is processed analogically to the real world, we conducted a study investigating virtual spatial processing in the brain using functional magnetic resonance imaging (fMRI). Results show differences in VR spatial brain processing as compared to known brain activations in reality. Identifying differences and commonalities of brain processing in VR reveals limitations and holds important implications for VR therapy and training tools. When VR therapy aims at the rehabilitation of brain function and activity, differences in brain processing have to be taken into account for designing effective VR training tools. Furthermore, for an evaluation of possible restoration effects caused by VR training, it is necessary to integrate information about the brain activation networks elicited by the training. The present study provides an example for demonstrating the benefit of fMRI as an evaluation tool for the mental processes involved in virtual environments.

Interactive blood damage analysis for ventricular assist devices.

Ventricular Assist Devices (VADs) support the heart in its vital task of maintaining circulation in the human body when the heart alone is not able to maintain a sufficient flow rate due to illness or degenerative diseases. However, the engineering of these devices is a highly demanding task. Advanced modeling methods and computer simulations allow the investigation of the fluid flow inside such a device and in particular of potential blood damage. In this paper we present a set of visualization methods which have been designed to specifically support the analysis of a tensor-based blood damage prediction model. This model is based on the tracing of particles through the VAD, for each of which the cumulative blood damage can be computed. The model's tensor output approximates a single blood cell's deformation in the flow field. The tensor and derived scalar data are subsequently visualized using techniques based on icons, particle visualization, and function plotting. All these techniques are accessible through a Virtual Reality-based user interface, which features not only stereoscopic rendering but also natural interaction with the complex three-dimensional data. To illustrate the effectiveness of these visualization methods, we present the results of an analysis session that was performed by domain experts for a specific data set for the MicroMed DeBakey VAD.