Evaluierung von Chinon- und Indigosulfonsäuren für organische Redox-Flow-Batterien

Eine große Herausforderung bei der Integration erneuerbarer Energien in das bestehende Stromnetz ist ihre diskontinuierliche und teilweise regional begrenzte Produktion. Um diese Schwankungen auszugleichen, kann die Energie bei einem Überangebot gespeichert und bei gesteigerter Nachfrage wieder in das Stromnetz eingespeist werden. Mit steigendem Anteil erneuerbarer Energien wird daher auch der Bedarf an Zwischenspeicherung immer bedeutsamer. Im Bereich der stationären Anwendung stellt die Redox-Flow-Batterie (RFB) eine vielversprechende Speichertechnologie dar. Zentrale Merkmale der RFB sind die räumliche Trennung des Ortes der Energiespeicherung vom Ort der Energieumwandlung sowie das Vorliegen der elektrochemisch aktiven Paare in fließfähigen Elektrolyten. Im Gegensatz zu anderen Batterien erfolgt bei der RFB die Energiespeicherung somit in der Elektrolytlösung und nicht im Elektrodenmaterial. Eine der zurzeit am weitesten entwickelten RFBs ist die Vanadium-Redox-Flow-Batterie (VRFB). In den letzten Jahren hat jedoch auch die Erforschung neuer, redoxaktiver organischer Spezies für den Einsatz in RFBs deutlich zugenommen. Der Fokus dieser Arbeient lag auf der Synthese von Indigosulfonsäuren, der Bestimmung grundlegender Eigenschaften von chinon- und indigosulfonsäurehaltigen Elektrolyten mit Schwefelsäure als Grundelektrolyt sowie auf der Prüfung ihrer Einsatzfähigkeit in einer Redox-Flow-Batterie. So konnte, basierend auf der literaturbekannten Synthese der Indigosulfonsäuren, die Aufarbeitung optimiert und ein vergleichbarer Syntheseweg für die strukturanalogen Thioindigosulfonsäuren entwickelt werden. In einem weiteren Schritt konnte dann das Redox-Potential und die Löslichkeit der Indigosulfonsäuren sowie ausgewählter Chinonsulfonsäuren im Grundelektrolyt ermittelt werden. Zudem wurden die elektrische Leitfähigkeit, die Viskosität, die Lichtstabilität und die thermische Stabilität des gesamten chinon- oder indigosulfonsäurehaltigen Elektrolyts bestimmt. Ausgehend von der Gegenüberstellung dieser als grundlegend angesehenen Eigenschaften der organischen Elektrolyte mit denen der vanadiumhaltigen Elektrolyte konnten geeignete Spezies für die Prüfung der Einsatzfähigkeit in einer Redox-Flow-Batterie identifiziert werden. Die durchgeführten Untersuchungen in einer Durchflusszelle haben gezeigt, dass von den betrachteten Spezies vier Verbindungen für den Aufbau einer konkurrenzfähigen, wasserbasierten organischen RFB geeignet sind.A major challenge in integrating renewable energy into the existing power grid is its intermittent and regional production. To compensate for these fluctuations, energy can be stored when there is an oversupply and fed back into the power grid later. Therefore, as the ratio of renewable energy increases, the need for intermediate storage becomes more significant. In the area of stationary applications, the redox flow battery (RFB) represents a promising storage technology. Central features of the RFB are the spatial separation of the site of energy storage from the site of energy conversion and the presence of electrochemically active species in liquid electrolytes. Unlike other batteries, energy storage in RFB thus occurs in the electrolyte solution rather than in the electrode material. Currently, one of the most advanced RFBs is the vanadium redox flow battery (VRFB). However, in recent years, there has also been a significant increase in the research and synthesis of new redox-active organic species for use in RFBs. The focus of this work was on the synthesis of indigosulfonic acids, determination of basic properties of quinone and indigosulfonic acid containing electrolytes with sulfuric acid as supporting electrolyte, and testing their applicability in a redox flow battery. Thus, based on the synthesis of indigosulfonic acids known from the literature, the purification was optimized and a similar synthetic route for the analogous thioindigosulfonic acids was developed. Afterwards, the redox potential and solubility of the indigosulfonic acids and selected quinonesulfonic acids in the supporting electrolyte were measured. In addition, the electrical conductivity, viscosity, light stability and thermal stability of the entire quinone or indigosulfonic acid containing electrolyte were determined. Based on the comparison of these properties of the organic electrolytes with those of the vanadium-containing electrolytes, it was possible to identify suitable species for use in a redox flow battery. Studies conducted in a flow cell showed that, of the species considered, four compounds are suitable for the construction of a competitive water-based organic RFB

Evaluation of options and limits of aqueous all-quinone-based organic redox flow batteries

Redox flow batteries based on aqueous electrolytes with organic active material (ORFB) have great potential for the development of environmentally safe and ecologically sustainable energy storage systems. To be competitive with the state-of-the-art vanadium redox flow battery, organic electrolytes must meet a whole range of requirements. We investigated different anthraquinone-based electrolytes, i.e. anthraquinone-2,6-disulfonic acid, anthraquinone-2,7-disulfonic acid (2,7-AQDS), anthraquinone-2-sulfonic acid, and 1,2-dihydroxybenzene-3,5-disulfonic acid (BQDS) with respect to their solubility in sulfuric acid, their electrical conductivity, and their viscosity. For this purpose, the influence of the concentration of sulfuric acid and the active species on the electrolyte properties was determined. Using NMR spectroscopy we analysed the thermal and electrochemical stability of 2,7-AQDS and BQDS electrolytes. The electrochemical stability was also monitored by cyclic voltammetry. Both methods have also indicated the absence of crossover phenomena. Furthermore, the influence of the electrolyte properties on the performance of the ORFB was investigated. Comparison with the vanadium electrolyte allowed us to estimate these kinds of requirements in order to develop a comparable all-organic flow battery

Biocompatibility of a polymer based on Off-Stoichiometry Thiol-Enes + Epoxy (OSTE+) for neural implants.

The flexibility of implantable neural probes has increased during the last 10 years, starting with stiff materials such as silicone to more flexible materials like polyimide. We have developed a novel polymer based on Off-Stoichiometry Thiol-Enes + Epoxy (OSTE+, consisting of a thiol, two allyls, an epoxy resin and two initiators), which is up to 100 times more flexible than polyimide. Since a flexible neural probe should be more biocompatible than a stiff probe, an OSTE+ probe should be more biocompatible than one composed of a more rigid material. We have investigated the toxicity of OSTE+ as well as of OSTE+ that had been incubated in water for a week (OSTE+H2O) using MTT assays with mouse L929 fibroblasts. We found that OSTE+ showed cytotoxicity, but OSTE+H2O did not. Extracts were analyzed using LC-MS and GC-MS in order to identify leaked chemicals

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Novel nanocarriers for topical drug delivery: investigating delivery efficiency and distribution in skin using two-photon microscopy

The complex structure of skin represents an effective barrier against external environmental factors, as for example, different chemical and biochemical compounds, yeast, bacterial and viral infections. However, this impermeability prevents efficient transdermal drug delivery which limits the number of drugs that are able to penetrate the skin efficiently. Current trends in drug application through skin focus on the design and use of nanocarriers for transport of active compounds. The transport systems applied so far have several drawbacks, as they often have low payload, high toxicity, a limited variability of inclusion molecules, or long degradation times. The aim of these current studies is to investigate novel topical drug delivery systems, e.g. nanocarriers based on cyclic oligosaccharides - cyclodextrins (CD) or iron (III)-based metal-organic frameworks (MOF). Earlier studies on cell cultures imply that these drug nanocarriers show promising characteristics compared to other drug delivery systems. In our studies, we use two-photon microscopy to investigate the ability of the nanocarriers to deliver compounds through ex-vivo skin samples. Using near infrared light for excitation in the so called optical window of skin allows deep-tissue visualization of drug distribution and localization. In addition, it is possible to employ two-photon based fluorescence correlation spectroscopy for quantitative analysis of drug distribution and concentrations in different cell layers

pKa Values for the Unfolded State under Native Conditions Explain the pH-Dependent Stability of PGB1

Understanding the role of electrostatics in protein stability requires knowledge of these interactions in both the folded and unfolded states. Electrostatic interactions can be probed experimentally by characterizing ionization equilibria of titrating groups, parameterized as pKa values. However, pKa values of the unfolded state are rarely accessible under native conditions, where the unfolded state has a very low population. Here, we report pKa values under nondenaturing conditions for two unfolded fragments of the protein G B1 domain that mimic the unfolded state of the intact protein. pKa values were determined for carboxyl groups by monitoring their pH-dependent 13C chemical shifts. Monte Carlo simulations using a Gaussian chain model provide corrections for changes in electrostatic interactions that arise from fragmentation of the protein. Most pKa values for the unfolded state agree well with model values, but some residues show significant perturbations that can be rationalized by local electrostatic interactions. The pH-dependent stability was calculated from the experimental pKa values of the folded and unfolded states and compared to experimental stability data. The use of experimental pKa values for the unfolded state results in significantly improved agreement with experimental data, as compared to calculations based on model data alone

Pharmacokinetic modeling of P-glycoprotein function at the rat and human blood--brain barriers studied with (R)-[11C]verapamil positron emission tomography.

ABSTRACT: BACKGROUND: This study investigated the influence of P-glycoprotein (P-gp) inhibitor tariquidar on the pharmacokinetics of P-gp substrate radiotracer (R)-[11C]verapamil in plasma and brain of rats and humans by means of positron emission tomography (PET). METHODS: Data obtained from a preclinical and clinical study, in which paired (R)-[11C]verapamil PET scans were performed before, during, and after tariquidar administration, were analyzed using nonlinear mixed effects (NLME) modeling. Administration of tariquidar was included as a covariate on the influx and efflux parameters (Qin and Qout) in order to investigate if tariquidar increased influx or decreased outflux of radiotracer across the blood--brain barrier (BBB). Additionally, the influence of pilocarpine-induced status epilepticus (SE) was tested on all model parameters, and the brain-to-plasma partition coefficient (VT-NLME) was calculated. RESULTS: Our model indicated that tariquidar enhances brain uptake of (R)-[11C]verapamil by decreasing Qout. The reduction in Qout in rats during and immediately after tariquidar administration (sevenfold) was more pronounced than in the second PET scan acquired 2 h after tariquidar administration (fivefold). The effect of tariquidar on Qout in humans was apparent during and immediately after tariquidar administration (twofold reduction in Qout) but was negligible in the second PET scan. SE was found to influence the pharmacological volume of distribution of the central brain compartment Vbr1. Tariquidar treatment lead to an increase in VT-NLME, and pilocarpine-induced SE lead to increased (R)-[11C]verapamil distribution to the peripheral brain compartment. CONCLUSIONS: Using NLME modeling, we were able to provide mechanistic insight into the effects of tariquidar and SE on (R)-[11C]verapamil transport across the BBB in control and 48 h post SE rats as well as in humans

Salting the Charged Surface: pH and Salt Dependence of Protein G B1 Stability

This study shows significant effects of protein surface charges on stability and these effects are not eliminated by salt screening. The stability for a variant of protein G B1 domain was studied in the pH-range of 1.5–11 at low, 0.15 M, and 2 M salt. The variant has three mutations, T2Q, N8D, and N37D, to guarantee an intact covalent chain at all pH values. The stability of the protein shows distinct pH dependence with the highest stability close to the isoelectric point. The stability is pH-dependent at all three NaCl concentrations, indicating that interactions involving charged residues are important at all three conditions. We find that 2 M salt stabilizes the protein at low pH (protein net charge is +6 and total number of charges is 6) but not at high pH (net charge is ≤−6 and total number of charges is ≥18). Furthermore, 0.15 M salt slightly decreases the stability of the protein over the pH range. The results show that a net charge of the protein is destabilizing and indicate that proteins contain charges for reasons other than improved stability. Salt seems to reduce the electrostatic contributions to stability under conditions with few total charges, but cannot eliminate electrostatic effects in highly charged systems