The power of the virtual client – using problem-based learning as a tool for integration in a pharmaceutical sciences laboratory course

This paper describes the design of a new practical class in pharmaceutical chemistry, which creatively guides the students through the subject area of physical and analytical sciences with the help of a ‘virtual client’. The design focuses on the active integration of knowledge and professional skills in an area which has been seen to be typically least popular with the students. The course is designed for a duration of 20 teaching weeks, categorized into four 5-week blocks, where the same set of learning outcomes are repeatedly approached from different angles. Students are provided with feedback and feed-forward points after each 5-week block. Evaluation of the design has shown that the students actively learn to integrate knowledge and positively engage with the practical and their ‘virtual client’. Engagement parameters, such as peer observations and marks, grades, and attendance are all very encouraging compared to traditional practical classes

Teaching large and diverse classes: a practice-based approach

Often we are asked to welcome more and more students into our lectures, seminars and other teaching units. This can be a real challenge, especially with the increasing diversity of our student body. As a group of academics, we decided to proactively approach this topic by conducting research into our students' feelings and anxieties while being taught in large classes. The aim was to introduce best practice and teaching excellence amongst academics, which we approached by producing an easily accessible education toolkit informed by our research findings. This problem is not exclusive to Reading or indeed to the UK; this is a topic discussed in higher education around the world. Attendance rates in lectures drop as students vote with their feet. Attainment drops as students disengage with the teaching. As we cannot ignore these facts it is important to pro-actively address them, identify the causes, and adjust our teaching to mitigate the risks.Oft werden Lehrende gebeten, immer mehr Studierende in Vorlesungen, Seminaren und anderen Lehreinheiten aufzunehmen. Dies kann eine echte Herausforderung sein, insbesondere mit der zunehmenden Vielfalt der Studierendenschaft. Eine Gruppe von Akademiker:innen um die Autorin hat beschlossen, dieses Thema proaktiv anzugehen, indem sie die Gefühle und Ängste der Studierenden während des Unterrichts in großen Veranstaltungen erforschen. Ihr Ziel war die Einführung von Best Practices und exzellenter Lehre, was sie durch die Erstellung eines leicht zugänglichen Bildungs-Toolkits, das auf ihren Forschungsergebnissen basiert, in Angriff nahmen. Dieses Problem gibt es nicht nur in Reading oder Großbritannien; es ist ein Thema, das in der Hochschulbildung auf der ganzen Welt diskutiert wird. Die Anwesenheitsrate in den Vorlesungen sinkt, da die Studierenden "mit den Füßen abstimmen". Der Lernerfolg sinkt, weil die Studierenden sich von der Lehre distanzieren. Da diese Tatsachen nicht ignoriert werden können, ist es wichtig, sie proaktiv anzugehen, die Ursachen zu identifizieren und die Lehre anzupassen, um die Risiken zu mindern

Titanocene anticancer complexes and their binding mode of action to human serum albumin: a computational study

Due to the pivotal role played by human serum albumin (HSA) in the transport and cytotoxicity of titanocene complexes, a docking study has been performed on a selected set of titanocene complexes to aid in the current understanding of the potential mode of action of these titanocenes upon binding HSA. Analysis of the docking results has revealed potential binding at the known drug binding sites in HSA and has provided some explanation for the specificity and subsequent cytotoxicity of these titanocenes. Additionally, a new alternative binding site for these titanocenes has been postulated

Hydrogen in metal nanoparticles : understanding and applying thermodynamic properties of metal-hydrogen nanostructures

The mobility sector is undergoing a fundamental change from fossil fuels through electricity to hydrogen. However, for hydrogen technology to be successful, the storage devices need to be pushed forward. Currently, the most promising path is to employ nanotechnology in metal hydride storage systems. This thesis presents different methods and material systems exploring the interaction of metallic nanoparticles and hydrogen. It aims to expand the limited literature knowledge about size dependent effects on thermodynamic and optical properties at the nanoscale. Several analytical and numerical models are developed and compared to own experimental data as well as existing literature. The experimentally investigated structures are palladium square patches, palladium-gold disk stacks, and yttrium nanorods. All structures throughout the thesis are characterized using plasmonic extinction spectroscopy, an optical measurement technique employing localized oscillations of the conduction electrons as a sensitive tool for structural and electronic changes in nanoparticles. The palladium square-patch investigations show a hydrogen loading pressure that is increasing with nanoparticle size, whereas the hydrogen induced in-plane expansion is decreasing with size. In the yttrium rod antenna studies, a drastic but reversible hydrogen induced elimination of the plasmonic resonance is observed, rendering the structure a highly interesting plasmonic switch. A sensitive plasmonic gas sensor is realized combining palladium nanoparticles with gold antennas. Through palladium-gold disk nanostacks that plasmonically behave as one superstructure, large hydrogen induced peak shifts of comparatively narrow resonances are demonstrated. Complementing the experimental findings, analytical models are developed for the isotherms of palladium nanoparticles and the plasmonic resonances of square nanopatches. The isotherm model reveals a coherent loading mechanism of palladium nanoparticles. In contrast, the unloading mechanism and the general bulk behavior follow incoherent transitions with a reduced hysteresis. The developed plasmon resonance model illustrates a method for obtaining broadband dielectric data of nanoparticles without prior knowledge of any material properties besides the particle geometry and the plasmon resonance wavelength. The findings presented in this thesis will be helpful to develop more efficient energy storage systems and powerful hydrogen sensors through well designed nanostructured devices.Mit der Verdrängung klassischer Verbrennungsmotoren durch elektrische Antriebe mit Batterie- oder Brennstoffzellentechnologie ist ein weltweiter fundamentaler Umbruch im Automobilsektor im Gange. Um die Brennstoffzellentechnologie jedoch zu einem langfristigen Erfolg zu führen, sind Innovationen in der Wasserstoffspeicherung notwendig. Eine Schlüsselrolle sollen dabei neue hocheffiziente Wasserstoffspeicher auf Metall-Hydrid Basis spielen. In dieser Dissertation werden metallische Nanopartikel und ihre Interaktion mit Wasserstoff mit Hilfe unterschiedlichster Methoden und auf Basis mehrerer Materialsysteme untersucht. Das Ziel ist dabei das begrenztes Wissen über größenabhängige Effekte thermodynamischer und optischer Eigenschaften auf der Nanoskala zu erweitern. Zu diesem Zweck werden unter anderem mehrere analytische und numerische Modelle entwickelt und mit eigenen experimentellen Daten sowie Literaturdaten verglichen. Experimentelle Studien, durchgeführt an Palladium Nanoquadraten, Palladium-Gold Nanoscheiben-Stapeln und Yttrium Nanostäben mit Hilfe von plasmonischer Extinktions-Spektroskopie, zeigen optische, elektronische und strukturelle Eigenschaften der jeweiligen Systeme und die dazugehörige wasserstoffabhängige Dynamik. So zeigt sich bei den untersuchten Palladium Nanoquadraten, dass der Wasserstoff Ladedruck mit zunehmender Größe der Teilchen zunimmt, während die wasserstoffinduzierte laterale Größenzunahme mit der Teilchengröße abnimmt. Die Untersuchungen an Yttrium Stabantennen zeigen ein drastisches aber reversibles wasserstoffabhängiges Ausschalten der plasmonischen Resonanz, was die Strukturen zu einem interessanten Kandidaten für einen plasmonischen Schalter machen. Des Weiteren wurde ein plasmonischer Wasserstoffsensors bestehend aus einer Kombination von Palladium und Gold Nanoscheiben realisiert und charakterisiert. Dabei zeigten sich abhängig von der Anordnung relativ große wasserstoffinduzierte Resonanzverschiebungen und gutes dynamisches Verhalten. Komplementär zu den durchgeführten experimentellen Studien wurden analytische Modelle für die Isothermen von Palladium Nanopartikeln, die Wasserstoffdiffusion in Yttrium Nanostäben und die plasmonischen Resonanzen in Palladium Nanoquadraten entwickelt. Das Isothermen Model offenbart, dass Palladium Nanopartikel bis zu einer gewissen Größe während der Wasserstoffabsorption einem kohärenten Phasenübergang folgen, während die Desorption von einem inkohärenten Phasenübergang begleitet wird, wie es bei großflächigem Palladium üblich ist. Das neuentwickelte Modell für plasmonische Resonanzen von Nanoquadraten kann dazu verwendet werden die dielektrische Funktion von Nanostrukturen über einen breiten Wellenlängenbereich experimentell zu bestimmen - nur durch Kenntnis der Geometrie und plasmonischen Resonanz der Strukturen aber ohne spezielle Annahmen über das Material zu machen. All die Erkenntnisse dieser Thesis können als kleine aber erkenntnisreiche Schritte zur Entwicklung effizienterer Energiespeicher und leistungsstarker Wasserstoffsensoren auf Nanostrukturbasis betrachtet werden

Long-term stability of capped and buffered palladium-nickel thin films and nanostructures for plasmonic hydrogen sensing applications

One of the main challenges in optical hydrogen sensing is the stability of the sensor material. We found and studied an optimized material combination for fast and reliable optical palladium-based hydrogen sensing devices. It consists of a palladium-nickel alloy that is buffered by calcium fluoride and capped with a very thin layer of platinum. Our system shows response times below 10 s and almost no short-term aging effects. Furthermore, we successfully incorporated this optimized material system into plasmonic nanostructures, laying the foundation for a stable and sensitive hydrogen detector

Analysis of three epoetin alpha products by LC and LC-MS indicates differences in glycosylation critical quality attributes, including sialic acid content

Erythropoietin (EPO) is one of the main therapeutics used to treat anaemic patients, greatly improving their quality of life. In this study, biosimilars Binocrit and a development product, called here CIGB-EPO, were compared to the originator product, Eprex. All three are epoetin alpha products, reputed to have similar glycosylation profiles. The quality, safety and efficacy of this biotherapeutic depend on the following glycosylation critical quality attributes (GCQAs): sialylation, N-glycolyl-neuraminic acid (Neu5Gc) content, branching, N-acetyl-lactosamine (LacNAc) extensions and O-acetylation pattern. Reverse-phase ultra high pressure liquid chromatography (RP-UHPLC) analysis of acid-released, 1,2-diamino-4,5-methylenedioxybenzene (DMB) labelled sialic acid derivatives and hydrophilic interaction liquid chromatography (HILIC) in combination with mass spectrometry (HILIC-UHPLC-MS) of procainamide (PROC) labelled N-glycans were the analytical tools used. An automated method for enzymatic release and PROC labelling was applied for the first time to the erythropoiesis stimulating agent (ESA) products, which facilitated novel, in-depth characterisation, and allowed identification of precise structural features including the location of O-acetyl groups on sialic acid (SA) moie-ties. Samples were digested by a sialate-O-acetylesterase (NanS) to confirm the presence of O-acetyl groups. It was found that Eprex contained the greatest relative abundance of O-acetylated derivatives, Binocrit expressed the least Neu5Gc, and CIGB-EPO showed the greatest variety of high-mannose-phosphate structures. The sialylation and LacNAc extension patterns of the three ESAs were similar, with a maximum of four N-acetyl-neuraminic acid (Neu5Ac) moieties detected per glycan. Such differences in SA derivatisation, particularly O-acetylation, could have consequences for the quality and safety of a biotherapeutic, as well as its efficacy

Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy

The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a natural flavonoid found largely in honey and passionflower on the modulation of platelet function, haemostasis and thrombosis. Chrysin displayed significant inhibitory effects on isolated platelets, however, its activity was substantially reduced under physiological conditions. In order to increase the efficacy of chrysin, a sulfur derivative (thio-chrysin), and ruthenium-complexes (Ru-chrysin and Ru-thio-chrysin) were synthesised and their effects on the modulation of platelet function were evaluated. Indeed, Ru-thio-chrysin displayed a 4-fold greater inhibition of platelet function and thrombus formation in vitro than chrysin under physiologically relevant conditions such as in platelet-rich plasma and whole blood. Notably, Ru-thio-chrysin exhibited similar efficacy to chrysin in the modulation of haemostasis in mice. Increased bioavailability and cell permeability of Ru-thio-chrysin compared to chrysin were found to be the basis for its enhanced activity. Together, these results demonstrate that Ru-thio-coupled natural compounds such as chrysin may serve as promising templates for the development of novel anti-thrombotic agents

Tripodal O-N-O bis-Phenolato Amine Titanium(IV) Complexes Show High In Vitro Anti-Cancer Activity

The octahedral titanium(IV) complexes trans,mer‐[Ti{R3N(CH2C6H2‐2‐O‐4‐R2‐6‐R1)2}2] (R1 = Me, OMe, Cl; R2 = Me, OMe, F, Cl; R3 = Me, Et; not all combinations) are synthesised in two steps from simple phenols in 36‐53% overall yield. The highly crystalline (4 X‐ray structures) complexes are active against MCF‐7 (breast) and HCT‐116 (colon) cancer cell lines showing widely varying GI50 values in the range 1‐100 µM depending on R1‐R3. Highest activities are realised when R1 = OMe and R2, R3 = Me (GI50 ~1 µM for MCF‐7 and 2‐3 µM for HCT‐116). These are respectively 8× and 3× times greater than the activities of cisplatin in the same cell lines. These titanium complexes show some significant selectivity for cancer cell lines; up to 7× higher in MCF‐7 compared to non‐cancer (MRC‐5) fibroblast cells. Details of cellular mode of action indicators (cell cycle perturbation, Annexin V, γ‐H2AX, and caspase studies) that point to an apoptosis mode for the most active compound (R1 = OMe and R2, R3 = Me) are also reported

Designing organometallic compounds for catalysis and therapy

Bioorganometallic chemistry is a rapidly developing area of research. In recent years organometallic compounds have provided a rich platform for the design of effective catalysts, e.g. for olefin metathesis and transfer hydrogenation. Electronic and steric effects are used to control both the thermodynamics and kinetics of ligand substitution and redox reactions of metal ions, especially Ru II. Can similar features be incorporated into the design of targeted organometallic drugs? Such complexes offer potential for novel mechanisms of drug action through incorporation of outer-sphere recognition of targets and controlled activation features based on ligand substitution as well as metal- and ligand-based redox processes. We focus here on η 6-arene, η 5-cyclopentadienyl sandwich and half-sandwich complexes of Fe II, Ru II, Os II and Ir III with promising activity towards cancer, malaria, and other conditions. © 2012 The Royal Society of Chemistry