Katharina Fromm
katharina.fromm@unifr.ch
+41 26 300 7000
https://orcid.org/0000-0002-1168-0123
Chemie in Lehre, Forschung, Public Outreach; Forschungspolitik; Forschungs- und Innovationsförderung; Forschungsevaluationen
Rektor_in
Rektorat
MIS 01 bu. 1210
Av. de l'Europe 20
1700 Fribourg
Av. de l'Europe 20
1700 Fribourg
MIS 01, 1210
Ordentliche_r Professor_in
Departement für Chemie
PER 10 bu. 114
Ch. du Musée 9
1700 Fribourg
Ch. du Musée 9
1700 Fribourg
PER 10, 114
Forschung und Publikationen
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Publications
227 Publikationen
Modelling the interaction between silver(I) ion and proteins with the 12-6 Lennard-Jones potential: a bottom-up parameterization approach
Valerie Mazan, Luca Manciocchi, Alexandre Bianchi, Mark Potapov, Katharina Fromm, Martin Spichty, Valérie Mazan, (2024) | Preprint4-[(E)-2-(1-Pyrenyl)Vinyl]Pyridine Complexes: How to Modulate the Toxicity of Heavy Metal Ions to Target Microbial Infections
Katharina M. Fromm, Justine V. Schwarte, Aurélien Crochet, Molecules (2024) | ArtikelFixative effect of 2‐oxo‐2‐phenylacetates in fine fragrance and eau‐de‐toilette applications
Damien L. Berthier, Jérôme Girard, Katharina M. Fromm, Andreas Herrmann, Flavour and Fragrance Journal (2024) | ArtikelCover image
Andreas Herrmann, Damien L. Berthier, Jérôme Girard, Katharina M. Fromm, Flavour and Fragrance Journal (2024) | ArtikelPhotophysical Properties of Anthracene Derivatives
Antoine Scalabre, Agonist Kastrati, Franck Oswald, Katharina M. Fromm, Photochem (2023) | ArtikelStimuli-Responsive and Antibacterial Cellulose-Chitosan Hydrogels Containing Polydiacetylene Nanosheets
Edwin Shigwenya Madivoli, Justine Veronique Schwarte, Patrick Gachoki Kareru, Anthony Ngure Gachanja, Katharina M. Fromm, Polymers (2023) | ArtikelStimuli Responsive and Antimicrobial Cellulose-Chitosan Hydrogels Containing Polydiacetylene Nanosheets
Edwin Shigwenya Madivoli, Justine Veronique Schwarte, Patrick Gachoki Kareru, Anthony Ngure Gachanja, Katharina M. Fromm, (2023) | PreprintChances and challenges of long‐distance electron transfer for cellular redox reactions
Bernd Giese, Maksym Karamash, Katharina M. Fromm, FEBS Letters (2023) | ArtikelA Rapid, Highly Sensitive and Selective Phosgene Sensor Based on 5,6‐Pinenepyridine
Atena B. Solea and Christophe Curty and Katharina M. Fromm and Christophe Allemann and Olimpia Mamula Steiner, Chemistry – A European Journal (2022) | ArtikelConference Report on the Nobel Symposium #168 “Visions of bio-inorganic chemistry: Metals and the molecules of life” held in Lejondal Castle, Sweden, from May 29 – June 1 2022
Katharina M. Fromm, CHIMIA (2022) | Artikel -
Forschungsprojekte
Bioinorganic Chemistry of Silver: Silver ion binding, silver ion and electron transfer in peptides and proteins
Status: LaufendBeginn 01.12.2022 Ende 30.11.2026 Finanzierung SNF Projektblatt öffnen This proposal is the prolongation of a project, ending end of March 2022. In order to allow for an overlap between the team, the current proposal is planned to start in January 2022. We are dealing with the bioinorganic chemistry of silver, an ion which has excellent antimicrobial properties with efficacy against bacteria, fungi and viruses, including SARS-CoV2, and an interesting therapeutic window in which it is tolerated by the human body. Although these effects are observed, they are not understood at the molecular level. This is why we set out to investigate several of these phenomena in more detail to generate a better understanding and control in the bioinorganic chemistry of silver. In a first part of this proposal, we are interested in silver binding peptides and how the binding affinity is influenced by the presence of certain amino acids nearby the binding site of the metal cation. The effects of charges in amino acid side groups, of their position and chirality with respect to the binding sites, as well as the influence of light, oxygen and pH on the stability of silver complexes will be studied together with the structural changes occurring in peptides upon silver ion binding. This will help in the basic understanding of silver ion binding to proteins, lead to a certain predictability and might also lead to applications in switching devices if e.g. coordination is reversible. Competition binding experiments between different peptides will be performed to see a) under which circumstances silver ions are bound, reduced or released, b) identify neighbour group effects in peptides, and c) how silver can be “handed over” from one peptide to another. These aspects are important also for the next part. The second part of the proposal is dedicated to the silver efflux pump system. Based on our recent findings on the unique SilE protein, we hypothesize its role as silver ion sponge AND chaperone, transporting the captured silver ions to a silver ion export system SilCBA. Based on current studies for silver ion transfer between SilE and SilB, we will now target silver ion transfer from SilE to SilA and SilC. As before, model peptides will allow to study molecular aspects and binding affinities for a fundamental understanding. A “strange SilA” described in the literature will also be included in the study. The third part is dedicated to the study of extracellular metal ion reduction by bacteria, in particular Geobacter sulfurreducens. The kinetic study of the reduction of silver and other metal ions has revealed some first insights into the chemistry of bacterial homeostasis and extracellular electron transfer processes, which will be further deepened in this proposal. It will include proteomics of Geobacter as a function of oxidant, understanding of how electron transfer takes place from one cytochrome to another and possibly the discovery and investigation of yet unknown cytochromes. All of the above investigations will help to understand the bioinorganic chemistry of silver, such as the antimicrobial effect and low cytotoxicity of silver. We will learn more about microbial defence mechanisms such as silver ion efflux and reduction via electron transfer processes and bacterial homeostasis. These very basic understandings lay the ground for better silver-based drugs that are important in times when the world has to deal with new viruses and super-resistant bacteria. NCCR Bio-Inspired Materials: Using Concepts from Nature to Create ‚Smart' Materials (phase III)
Status: LaufendpH responsive chitosan – cellulose hydrogels for wound dressing applications
Status: AbgeschlossenBeginn 01.03.2022 Ende 31.08.2022 Finanzierung SNF Projektblatt öffnen An ideal wound dressing should provide mechanical protection, maintain a moist environment, be easily removable without causing trauma or pain, be cost effective and most importantly minimize the development of infection from bacteria which are a major problem. Many products currently in the market meet a selection of these criteria, but the most challenging aspects of wound management, effective treatment of bacterial infection, is a work in progress. Alginate and Chitosan nanocomposites have been investigated as abundant, bio-based and renewable feedstock for the development of wound dressings and medical sutures. Our work will demonstrate antibacterial carboxymethylchitosan-alginate-Ciprofloxacin wound dressing platforms for chronic wound management as an alternative to conventional dressings. Research Semester: Trying out new ideas
Status: AbgeschlossenBeginn 01.01.2020 Ende 30.06.2020 Finanzierung SNF Projektblatt öffnen The research semester will allow me, after 9 years of serving as a Research Councillor for SNSF, to reconnect with my science, to write up research results for publication and to try out new ideas. First results of my Division II project on bioinorganic silver need to be written up. We are studying here the antimicrobial effect of silver and possible resistance aspects. For the silver efflux pump study, we learned how to synthesize large peptides, how to express proteins from E. coli and how to analyze the binding of these peptides and proteins with silver. We will furthermore profit from the collaboration with the NMR experts at the University of Lyon. Another project in my group to push forward into applications is the finding of a cork taint, explosive and pesticide detector. For this, an Innosuisse project needs to be written. “Experience Art & Science” - INTEGRATIVE HUMAN HEALTH DAY
Status: AbgeschlossenBeginn 01.10.2019 Ende 31.10.2019 Finanzierung SNF Projektblatt öffnen Artists and scientists may have in common that their art or science is obscure to the large public. Surprisingly few interactions exist between scientists and artists. We are convinced that both, Art and Science can improve creativity in all domains by bringing new tools and new ideas. This conviction is strengthened with the example of the "Bauhaus" movement that included Arts and revolutionized Architecture and industrial design. The Swiss Integrative Center for Human Health (SICHH) is building an art & technology communication platform named “Experience Art & Science” (EAS) that will be launched the 5th October 2019 in the Blue Hall, BlueFACTORY, Fribourg. This launch event is aimed for the large public. To create a link between Art and Science, our approach will be to mix Art and Science to speak to the public. We will present two Shows to the public, one with a story about questing quick regeneration illustrated with chemical experiences and one artistic performance whose inspiration will be rooted in Science. While the Art show will involve Billy The Artist, the Chemistry show will be managed by Katharina M. Fromm. To complement the shows, we will also propose a series of workshops dedicated to the large public offering them a full immersion day in science, technology and art. Theses interactive workshops are centered on the visualization of science through art and involve experts in science with expertise in public outreach such as Dr. Isabelle Dupanloup Duperret (expert in Digital Health), Dr Christina Martin Olmos (expert in microscopy) and experts in art like EIKON (professional school of applied arts in Fribourg). Our aim is to lower the threshold of communication between Science, Art and the large public. Ideally, we would also like the public to acquire a positive interest in Science and technology. GACAPS
Status: AbgeschlossenAdaptive functional polymers and nanocontainers
Status: AbgeschlossenNCCR Bio-Inspired Materials: Using Concepts from Nature to Create ‚Smart' Materials (phase II)
Status: AbgeschlossenBioinorganic Chemistry of Silver: Biomineralization, Silver Resistance, Antimicrobial Activity and more
Status: AbgeschlossenBeginn 01.05.2018 Ende 30.11.2022 Finanzierung SNF Projektblatt öffnen Silver is known for its antimicrobial properties since ancient times and was used in medical applications until the 1940s, when antibiotics were discovered. Forgotten until the upraise of antibiotic-resistant bacteria, it has since seen a revival in research. With the use of silver e.g. in wound dressings, silver-resistant bacteria emerged. Resistance may occur e.g. via expression of an efflux pump, while other bacteria are able to reduce ionic silver to silver nanoparticles (AgNPs). This research project copes in part A with the design of improved silver-based antimicrobial coordination compounds by combining the action of silver with another antibacterial metal ion, e.g. Cu2+ and Zn2+. To achieve this goal, we will use biocompatible ligands that possess two different binding sites. Dual action compounds are expected to be more efficient, also against Ag-resistant bacteria. Compounds will be characterized in solution and the solid state by NMR titration studies, single crystal structure analysis, UV-Vis, IR, elemental analysis and tested for antimicrobial and cytotoxic properties. To follow the compounds in cells, newly developed luminescent ligands allow monitoring via confocal fluorescence microscopy. It is at the same time important to understand the silver-resistance mechanisms of bacteria. In part B, we will continue to investigate the silver efflux pump Sil of some Gram-negative bacteria, in particular the unique periplasmic SilE protein whose role is still not fully understood (Ag+ binding with SilE and how Ag+ is exported). Another mechanism by which bacteria can reduce the toxicity of silver ions is by generating AgNPs outside of the cell (biomineralization), either at the membrane using cytochromes, or at the pili via electron transport through proteins (part C). For both the efflux pump and the biomineralization processes, we will start with model peptides to approach the full protein bottom-up. We have shown this technique successfully in a first study on short peptide excerpts from SilE, using NMR-titrations and competition fluorescence titrations for the determination of the Ag+ binding constants. Larger model peptides will lead us to a final understanding of the proteins themselves, hence of the mechanisms. Studies of the biomineralization at different concentrations will help to establish the electron transfer rates through the membrane to AgNPs. Understanding the antimicrobial and the silver resistance mechanisms is important for the future development of active compounds. Characterization of Biomolecules by Mass Spectrometry
Status: AbgeschlossenBeginn 01.01.2018 Ende 31.12.2018 Finanzierung SNF Projektblatt öffnen January 2017 the joined Metabolomics/Proteomics Platform (MAPP) of the Department of Biology, University of Fribourg was officially launched (https://www.unifr.ch/go/mapp). The aim of MAPP is to provide all research groups of the University of Fribourg and the associated NCCR Bio-Inspired Materials with mass spectrometry (MS) expertise. So far, the offered services include quantitative expression proteomics analyses, analyses of protein-protein interactions by affinity-purification (AP)-MS, characterization of posttranslational modifications (PTMs) including phosphorylation and ubiquitination, and the analysis of lipids and lipophilic metabolites. Currently MAPP is equipped with two liquid chromatography (LC)-MS/MS systems, of which one, a 12 year old LTQ-Orbitap Classic, is outdated and only used for method development. Thus, almost the entire workload is handled by one Q-Exactive Plus system, which creates a serious bottleneck in sample throughput and causes increasingly long waiting times. We apply for a new generation Thermo Scientific Q-Exactive HF system offering enhanced resolution and sequencing speed. We exemplify with eight diverse research projects that this state-of-the-art system is essential for the future functioning of MAPP and for the entire natural science community in Fribourg: Project 1 characterizes ubiquitination-dependent signaling events in stress-induced autophagy employing human cell culture systems. Autophagy is an essential cellular turnover path-way often deregulated in human diseases such as cancer and neurodegeneration. Project 2 studies phosphorylation-dependent signaling events regulating cell growth. Using yeast Saccharomyces cerevisiae as model the TORC1 signaling network is analyzed mechanistically. In Project 3 we employ crosslinking MS to study the topology of membrane proteins and how it changes upon movement from the lipid bilayer of the endoplasmic reticulum onto the putative monolayer membrane of lipid droplets. Project 4 deals with the role of the transcription factor Creb (cAMP-response-element binding protein) in long-term memory formation using Drosophila melanogaster as model system. In Project 5 top-down MS is applied to study the regulation of small molecular neurotransmitters, neuropeptides and proteins in animal models of major depression disorder. Project 6 characterizes organelles and protein-protein interactions important in arbuscular mycorrhizal symbiosis in the model plant Petunia hybrid. In Project 7 we investigate the antimicrobial effects of silver ions and silver nanoparticles and how the gram-negative bacterium Geobacter sulfurreducens copes with it. Project 8 aims at characterizing the cellular uptake of newly developed nanoparticles and their interaction with serum and cellular proteins. Thus, with these projects we cover the major research areas in Fribourg having need for a state-of-the-art LC-MS/MS system and highlight the importance of MAPP for the research location Fribourg. European Crystallography Meeting ECM-30
Status: AbgeschlossenBeginn 01.07.2016 Ende 30.09.2016 Finanzierung SNF Projektblatt öffnen European Crystallography Meeting ECM-30 SupraMedChem@Balkans.Net: Biomedical Dimension of Supramolecular Chemistry in the training and research in the Balkans area
Status: AbgeschlossenBeginn 01.07.2015 Ende 30.11.2018 Finanzierung SNF Projektblatt öffnen Supramolecular chemistry offers the design of molecular information-controlled, "programmed," and functional self-organizing systems, and provides an original approach to nanoscience, as well as a powerful alternative/complement to nanofabrication, nanomanipulation and drug delivery. All this makes supramolecular chemistry a truly multidisciplinary research subject with great potential for the future development -and logically brings the need for suitable teaching. This training at the level of young researchers and students cannot possibly encompass all biomedical aspects of the supramolecular idea, but must concentrate on the achievements reached with synthetic ligands interacting with biological systems. Following this concept it is clear that the teaching cannot give illustration of all aspects of non-covalent assemblies in the biomedical field. And there is no need to do that! It is enough to make visible, for the young people, the unlimited possibilities of using intermolecular interactions in living systems and to inspire them. The inspiration is the building stone of the current proposal. In this Institutional Partnership we unite the efforts of the Department of Chemistry and the Adolphe Merkle Institute (AMI) (University of Fribourg), the Faculty of Science (University of Kragujevac) and the Institute of Organic Chemistry (Bulgarian Academy of Sciences) in creating of suitable educational background for teaching in supramolecular chemistry and its biomedical applications in the Balkan area. This geographic area, for long time a synonym of violence and instability, is now in a process of transition, success of which crucially depends on the availability of well-educated, motivated, beyond geographical borders minded young people. With SupraMedChem@Balkans.Net we plan to create a solid background in the modern teaching in supramolecular chemistry and to implement the best Swiss educational and research standards. This will be achieved by a three layers approach: - Teaching activities (basic layer), which aim to develop new curricula for teaching in supramolecular chemistry and to provide conditions for training in the general concepts of supramolecular chemistry by organizing Summer/Winter schools; - Training initiatives (upgrade layer), which are directed to increase the capacity of the staff of the partner institutions to do research and education in biomedical supramolecular chemistry through personnel exchange and organizing workshops; - Strengthening the research and renewal of the infrastructure (sustainable development layer) in order to strengthen the training and research capacity of the participating Balkan institutions. Number of important outcomes is expected in respect of the institutional capacity building, but the most substantial benefits are expected for the young people (high school and university students, PhD students and young researchers). This IP provides a unique opportunity to build up an educational profile and research career. We will provide basic (Summer schools) and advanced (Workshops and exchange scheme) teaching by using the complementary expertise (solid state – solution – gas phase; theory – experimental studies) of the partner groups. Through the exchange schemes the trainees will have the opportunity to work in different scientific and cultural environment, to establish new contacts and friendships and to acquire new skills in the research and management. The proposal unites 3 successful research teams, working actively in experimental supramolecular chemistry, and gives a clear perspective for strengthening their research and teaching by creating condition for expansion in the biomedical direction and for collaborative networking in future. New rechargeable metal-water and metal-air batteries: fundamental science & feasibility
Status: AbgeschlossenBeginn 01.10.2014 Ende 30.11.2017 Finanzierung SNF Projektblatt öffnen This joint proposal between the group of Prof. Park, ETHZ and Prof. Fromm, Uni Fribourg, deals with the development of new carbon-nanotube-based membranes as well as electrolytes that will be used in the context of lithium (metal)-water or metal-air batteries. These batteries possess an enormous theoretical energy density of ca. 10'000 Wh/kg, of which only a fraction can be exploited with today's technology. Within the frame of the SCCER Heat and Energy Storage to which we contribute in Work Package 1, we will develop new Li-water and Li-air batteries by developing new membranes and electrolytes which allow the safe use of such systems and excluding unwanted side-reactions. Functional Polymers though Mechanochemistry
Status: AbgeschlossenNCCR Bio-Inspired Materials: Center for Bio-Inspired Stimuli-Responsive Materials (phase I)
Status: AbgeschlossenBeginn 01.06.2014 Ende 31.05.2018 Finanzierung SNF Projektblatt öffnen ”Intelligent” materials, which change their properties in a selective manner in response to external stimuli, are of fundamental scientific interest and potentially useful in countless applications. Scientists have begun to consider the structurally complex, often multifunctional and highly specific res¬ponsive materials found in Nature as inspiration for the design of artificial materials with stimuli-responsive properties. Recognizing that the innovation potential in this domain is huge, that a large-scale interdisciplinary effort is required to realize paradigm-changing scientific breakthroughs, and that the time is right to launch such an activity in Switzerland, a National Competence Center for Bio-Inspired Stimuli-Responsive Materials is proposed. The proposed Center merges chemistry, physics, materials science, biology, and medicine to study and apply new bio-inspired stimuli-responsive materials with an overarching goal to establish new design rules and strategies for their creation. Another goal is to develop a predictive understanding for their interactions with cells and to apply the knowledge generated to diagnostics, (cancer) therapy, and combinations thereof (“theranostics”). Research will be in three interdisciplinary modules that focus on mechanically responsive materials, responsive materials made by self-assembly, and the interactions of responsive materials with living cells. The interconnection of these themes will create tremendous opportunities, which can only be harnessed if addressed within a multidisciplinary center with a long-term research vision. The proposed Center combines multiple research groups from the Universities of Fribourg, Geneva and Basel and from EPFL and ETHZ. The Center is well aligned with the strategic thrusts of the Home Institution in the areas “Nanomaterials” and “Life Science and Biomedicine” and it will have a considerable impact on the development of the University of Fribourg’s Faculty of Natural Sciences. The center will offer comprehensive programs and structures to support education, knowledge and technology transfer, and the advancement of young researchers and women. Key elements include Undergraduate Research Internships, a new Master’s Program focused on soft materials, Graduate Student Exchanges with partners in the USA and China, Independence Grants for Young Researchers, a pre-competitive Industrial Associates Program, and a Proof-of-Concept Grant Program. These and other measures drive the research from fundamentals to applications, support a sustainable development of the NCCR, and promise maximal societal impact. With a scientific focus and scope that are unparalleled in Switzerland, the proposed Center is uniquely positioned to become an internationally recognized hub for smart materials research, education, and innovation. Coordination Compounds: From Basics towards Applications in Materials and Medicine
Status: AbgeschlossenBeginn 01.04.2014 Ende 31.08.2018 Finanzierung SNF Projektblatt öffnen The proposal is divided into two main parts. The first part deals with the synthesis and properties of mixed metal compounds, either as zero-dimensional aggregates (clusters) or as coordination polymers. For the former, we will investigate the cluster properties as well as their capability to yield ceramic nanomaterials upon combustion. For the coordination polymers, we will investigate properties as well as the design of porous coordination polymers based on new ligand classes. The second part of the proposal deals with the coordination chemistry of silver with peptides and tackles with the bioinorganic chemistry of silver, the formation of silver nanoparticles with light and the development of new soft matter materials (hydrogels and polymers) with antimicrobial properties. Entlastungsbeitrag
Status: AbgeschlossenArgent antibactérien (CTI 15856.1 PFNM-NM)
Status: AbgeschlossenSilver Wires: Design of linear Ag complexes by using tautomeric ligands
Status: AbgeschlossenGrundlagenforschung und Anwendung: von Ionenkanälen und porösen Festkörpern über 'Cluster' zu Biomaterialien
Status: AbgeschlossenBeginn 01.04.2013 Ende 31.03.2014 Finanzierung SNF Projektblatt öffnen Fundamental Research and Applications: From Ion Channels and Porous Solids via 'clusters' to Biomaterials Chances and Risks of Nanoscale Electrode Materials for Li-Ion-Batteries
Status: AbgeschlossenBeginn 01.06.2012 Ende 30.04.2016 Finanzierung SNF Projektblatt öffnen Energy production and storage are important issues for humanity. While Li-ion-batteries are well established as energy storage systems for small devices, they are not yet very present in larger applications like cars. We intend to develop new composit materials in order to make electrode materials i) more efficient and b) less toxic. Composit materials have the advantage of rendering the electrodes more conductive, lighter and more efficient as less active material is required per volume. We will make nanoscale electrode materials, develop composits which improve the electrode properties and test these batteries for their performance. On the other hand, we will also and in parallel develop methods for the recycling of such nanoparticle-containing materials. R'Equip grant proposal for a MALDI ToF mass spectrometer
Status: AbgeschlossenBeginn 01.04.2012 Ende 31.03.2013 Finanzierung SNF Projektblatt öffnen R'Equip grant proposal for a MALDI ToF mass spectrometer High resolution X-ray diffractometer for the structural analysis of thin films, heterostructures and nanoparticles at variable temperatures
Status: AbgeschlossenBeginn 01.03.2012 Ende 28.02.2013 Finanzierung SNF Projektblatt öffnen High resolution X-ray diffractometer for the structural analysis of thin films, heterostructures and nanoparticles at variable temperatures Antimicrobial silver surface treatment of orthopaedic implants
Status: AbgeschlossenNanoscale science on surfaces
Status: AbgeschlossenSupraChem@Balkans.eu : Supramolecular training for students and young researchers in the Balkan area
Status: AbgeschlossenBeginn 01.01.2012 Ende 31.12.2014 Finanzierung SNF Projektblatt öffnen SupraChem@Balkans.eu : Supramolecular training for students and young researchers in the Balkan area IncuCyte-based high throughput imaging-based platform for determination of cellular and molecular events in real time in cultured cells in vitro: application to nanomaterial studies, cancer and cardiovascular research
Status: AbgeschlossenBeginn 01.12.2011 Ende 30.11.2012 Finanzierung SNF Projektblatt öffnen IncuCyte-based high throughput imaging-based platform for determination of cellular and molecular events in real time in cultured cells in vitro: application to nanomaterial studies, cancer and cardiovascular research New anti-bacterial coatings for implant materials
Status: AbgeschlossenBeginn 01.10.2011 Ende 31.03.2014 Finanzierung SNF Projektblatt öffnen New anti-bacterial coatings for implant materials Conditional triggered drug release
Status: AbgeschlossenBeginn 01.07.2010 Ende 28.02.2015 Finanzierung SNF Projektblatt öffnen The number of patients requiring joint replacement or internal fixation devices is steadily increasing. E.g. in the U.S., 600’000 joint prostheses and 2 million fracture fixation devices are implanted every year. Infections of these implants can become a very serious problem, the infection rate being ca. 1-2% for hip or knee implants, and up to almost 20% for pacemakers. These infections frequently occur perioperatively by bacterial contamination of the surgical site, which form biofilms, allowing bacteria to resist antimicrobial agents and immune responses. We therefore propose to develop new materials which i) release drugs only when and where they are needed, ii) dramatically reduce the percentage of implant infection, iii) decrease the trend of resistance build-up by bacteria, iv) reduce health costs, v) improve the quality of life for patients, and vi) yield new products to be produced and sold by manufacturers of implants and fracture fixation devices. In two work packages, we will i) develop a concept of drug-filled nanocontainers attached to a (coated) implant surface and ii) bacterial sensors which shall trigger increased drug release from these nanocapsules. Towards a more bulk sensitive photoemission experiment
Status: AbgeschlossenBeginn 01.06.2010 Ende 31.05.2013 Finanzierung SNF Projektblatt öffnen For the microscopic understanding of new materials, the photoemission experiment is unique in its possibility to probe the energy and momentum distribution of electrons responsible for various unexpected and interesting properties of materials. It also offers to probe the local atomic/crystallographic structure via photoelectron diffraction. However, photoemission is intrinsically surface sensitive due to the limited mean free path of escaping photoelectrons and, in cases, it may be doubtful to "practice" bulk physics based on photoemission results. Therefore, this project is concerned with enhancing the bulk sensitivity of the photoemission experiment in order to probe true bulk or interface properties with respect to the atomic/crystallographic and electronic properties. We intend to concentrate our activities on topics a), b) and c) described below. a) Oxide based materials / heterostructures and multilayers: These are emerging materials with both, very high potential for applications and a desperate need for better understanding the physics behind the rich phenomenology. Photoemission experiments are very promising to significantly increase insight, provided we can render them more bulk sensitive. b) Low dimensional systems, layered compounds: These are materials where we search for a better understanding of phenomena like the formation of charge density waves, superconductivity, quasi-particles and electron correlations, based on models made for the bulk material. However experimental information obtained from photoemission mostly stems from the surface. Again it is desirable to collect the same detailed information relevant for the bulk. c) Further areas of interest, molecules and minerals: Here we search to apply photoemission experiments to materials relevant in a cross disciplinary context. These range from molecular systems where photoemission may determine the valence of an element to minerals where the behavior of particular constituents or ingredients is of strong interest. Grundlagenforschung und Anwendung: von Ionenkanälen und porösen Festkörpern über schaltbare Moleküle zu Biomaterialien
Status: AbgeschlossenBeginn 01.04.2010 Ende 31.03.2013 Finanzierung SNF Projektblatt öffnen Being a continuation of previous projects, this project deals again with at first sight very different areas evolving from the areas, in which we have made progress over the past years. In the first part, we wish to close the current gap which exists between crystalline coordination polymer networks requiring relatively short and rigid ligands, and polymers with their corresponding properties. To do so, the plan is to stepwise increase the length of the flexible spacer used in our ligand types, while binding these ligands still to the same metal ions, in our case mainly silver or copper ions. With this strategy, we hope to be able to come across compounds with new properties for our systems, e. g. with liquid crystalline properties. As the ligands become larger, we furthermore plan to investigate systems with larger metal ion nodes. For this purpose, we propose i) metal ion cluster compounds, e. g. molecular magnets, or ii) nanoparticles, the latter of which can be either used as starting material or be generated in situ by irradiation with light (or chemical reduction). Such truly hybrid materials made of a medium to large sized functional ligands and nanoparticles on the other hand can lead to stimuli-responsive systems, which can change structurally as well as the properties e. g. upon mechanical stress or addition of specific metal ions. Such property changes can then be fine-tuned by the nanoparticle size and composition, as well as the ligand structure. The mobility of nanoparticles in polymer matrices will be studied in order to detect and understand self-healing processes, more specifically the migration of nanoparticles in a polymer matrix towards cracks or other defects in the polymer structure. First promising tests have been made in these directions which we now plan to follow up in detail. The next part of the project deals with the synthesis, characterization and analysis of porous compounds for the selective absorption of guest molecules. Apart from our channels systems obtained with simple crown ether molecules and calix[n]arenes, for which we were able to show that they possess ion and water conducting properties, we also developed a number of new metal-organic frameworks, some of them with large pores and reversible gas uptake and release properties. We have also developed the synthesis of tetrasubstituted dibenzo-18-crown-6, for which we have lately obtained first results with coordinated metal ions. In spite of their poor solubility, we are since recently able to obtain coordination polymers with such complicated ligand systems, and this research field has to be explored in more detail. Furthermore, we are currently developing asymmetrically substituted crown ether ligands to be included into polymers on one hand and able to coordinate metal ions within the crown, but also at one substituted pyridyl moiety. This will allow for the construction of selective mixed metal ion binding polymers. With calixarene ligands, we have recently started to investigate the radical formation as indicated in the previous proposal. We want to use this reactivity of calixarenes, which is similar to the one of phenoly, or, in natural systems, tyrosine in relation to reducible transition metal ions. Photo-labile functional groups are also of interest in our molecular cluster compounds. We have recently obtained a number of small cluster compounds with phenolate and paramagnetic ions, and in which these ions are arranged in triangles or chains. Introducing a photo-labile group in para position of the phenol function and subsequent irradiation will lead to the formation of radicals on the ligand oxygen atom, inducing further paramagnetic ions. We are interested here in the resulting magnetic properties. Furthermore, such clusters may serve as nodes in the construction of coordination polymer networks. Conditioned triggered drug release
Status: AbgeschlossenNeue antibakterielle Oberflächen auf Implantat- Materialien
Status: AbgeschlossenBeginn 01.10.2008 Ende 30.09.2011 Finanzierung SNF Projektblatt öffnen In all European countries, the numbers of patients requiring joint replacements are rapidly increasing, e.g. by 6% in the UK. Devices are increasingly inserted in patients to relieve pain or improve function or for esthetic reasons. These implants can be foci for infection, which still represents one of the most serious and devastating complications, forcing patients back to surgery for infection control and/or implant replacement. Even though operating conditions are excellent in developed countries, the infection rate due to bacterial adhesion and biofilm formation is still relatively high, ranging from 1-2% (hip/knee prosthesis) to 15% (fracture fixation devices), and increasing antibiotic resistance of bacteria point to higher infection percentages in the future. The cost of such interventions is ca. CHF 75’000 per episode with a high risk of relapse (~10%), meaning a heavy load to health insurers, not to mention the impact on society when patients are on sick leave. In this context the development of new bioactive surfaces, aimed to reduce the high vulnerability of the interstitial milieu between implant and surrounding tissue, has a large impact on a growing medical problem, quality of patient life, and an opportunity for the production of new marketable technologies. In the first part of this project we elaborated a standard synthesis for silver coordination polymer networks and a coating method for their deposition as nanostructured coating for the metal implant materials Ti, stainless steel and Au alloys. It was proven that our coatings possess anti-bacterial activity against S. sanguinis and S. epidermidis in vitro. Standard protocols to investigate the mechanical and biocidal properties of the compounds were elaborated. These studies have to be extended with i) other and new silver coordination compounds, including complexes of Ag+ with antibiotics, ii) other bacterial strains with and without biofilms for completeness, iii) systematic investigations on the mechanism of action of the compounds on the bacteria, using mutants as well as different screening methods such as agarose plates, confocal microscopy, microand nano-calorimetry and iv) in vivo studies of our promising candidates giving insights into real-life measurements, pharmaco-kinetics, and biocompatibility. To realize this project, we propose an interdisciplinary research team consisting of a chemist (synthesis and analysis), a material scientist (biomechanics, calorimetry), a microbiologist/infectious diseases specialist (in vitro and animal studies) and an orthopedic surgeon (in vitro). Chemical vapour deposition system for in situ growth and AFM/STM investigation of tailor made composite thin films and devices with new properties
Status: AbgeschlossenBeginn 01.07.2007 Ende 31.12.2008 Finanzierung SNF Projektblatt öffnen We propose an ultra high vacuum (UHV) system, which allows the deposition of organic material, metal-organic compounds, and metals for the generation of thin films. Our goals are i) to study the chemical and physical properties of such films, compared to bulk materials in the first step; ii) secondly to study possible transformations of our compounds into functional oxides; iii) and, finally, to combine the different materials into new devices. The proposed UHV system consists of two different deposition chambers, one for organic compounds, the other for metal containing materials, both being connected via an UHV transfer chamber for the growth of heterostructures without breaking the vacuum. It will also enable us to complete the system with in situ surface analytical methods (AFM/STM), and to connect it to the existing pulsed laser deposition (PLD) system (group Bernhard). It allows the generation of complex devices from sources requiring different evaporation temperatures and techniques. This system will strongly enhance synergies between the Departments of Chemistry, Geosciences, and Physics at the University of Fribourg, as well as the Fribourg Centre of Nanomaterials, FriMat. It will complete the already existing solid state deposition techniques used in the Chemistry Department and FriMat, like chemi- and physisorptions, dip-coating (group Fromm), Langmuir-Blodgett films (group Albrecht), high-vacuum sputtering (group Grobéty), PLD (group Bernard). In particular, the proposed UHV transfer chamber will allow us to combine these techniques for the in situ growth and characterisation of devices. The physical properties of these new materials will be jointly investigated by IR-to-UVellipsometry, low-energy muon spin rotation, neutron reflectometry, magneto transport and standard magnetisation (group Bernhard) and x-ray, classical spectroscopies and thermo gravimetric techniques (TG/DTA/DSC, groups Fromm, Jenny, Bochet). 1) Deposition of metal organic compounds and related oxides (group Fromm) (a) Layers of nanocrystalline alkali, alkaline earth and transition metal oxides. We will use our volatile alkoxide/aryloxide alkali and alkaline earth metal compounds as precursors for the generation of corresponding oxides which are frequent ingredients to oxide materials, such as high Tc superconductors (for instance YBa2Cu3O7- d ) or ferroelectrica (i. e. BaTiO3). Analogue clusters of transition and lanthanide metal M2+ ions will be used to deposit corresponding metal oxides, i.e. the generation of half metallic CrO2, and magnetic clusters. (b) Deposition of low-dimensional transition metal coordination compounds. Low-dimensional coordination compounds between metal ions and organic ligands may exhibit polymorphism in the bulk. Deposition of such compounds on surfaces might lead to even more new structures, and therefore also to new properties of the deposited material. We will first test this with our silver compounds, and study their antimicrobial properties as thin films on implant materials. Furthermore, this project will be extended to the deposition of low-dimensional structures with magnetic ions such as manganese, copper, nickel, cobalt and lanthanides, generating geometrically spin frustrated Kagomé lattices. We generally expect a more regular and better coating using the CVD method as compared to sol-gel deposition, and would require surface analysis like AFM and STM to prove so. 2) Deposition of organic compounds (groups Bochet and Jenny) Organic conductors as well as light sensitive molecules shall be deposited in this part of the project. Masks will allow a precise positioning of the materials which can be switched as logic gates depending on the wavelength used to irradiate the deposited material. 3) New spintronic oxide-organic devices (collaboration with group Bernhard/Drew). We will grow spin valve structures with metallic and oxide based electrodes, and investigate their spin injection and diffusion phenomena. Grundlagenforschung und Anwendung: von Ionenkanälen und porösen Festkörpern über schaltbare Moleküle zu Biomaterialien
Status: AbgeschlossenBeginn 01.04.2007 Ende 31.03.2010 Finanzierung SNF Projektblatt öffnen This research proposal deals with at first sight very different areas, but which have all evolved from our current research, and which focus now on possible applications. The first proposal deals with the synthesis, characterization and analysis of selective porous compounds. We have synthesized channel systems with dibenzo-18-crown-6 (DB18C6) molecules which can transport either H2O or NaOH through single crystals via pores arranged in one dimension. With calix[8]arene, the obtained 1D-channels are larger and can transport ions and water simultaneously. We now intend to synthesize substituted crown ether ligands which allow to build up relatively rigid coordination polymers with selective channel functions in order to allow i) directional ion and/or water conduction and ii) selective binding of substrates. These ligands can coordinate to different metal ions, forming porous coordination polymer compounds which are expected to conduct ions/molecules in more than one defined direction. Our elongated ring-shaped molecules obtained in Ag-coordination chemistry are planned to be substituted with long alkyl chains in order to increase the structural anisotropy at the molecular level. This is expected to lead to liquid crystalline behavior. Also, calix[n]arene molecules are to be derivatized at the upper rim with i) long alkyl chains for the possibility to obtain liquid crystals, monolayers or micelles, and ii) functional groups which allow the integration of these macrocyclic ligands into polymers, iii) photo-labile groups to trigger (switch on/off) functionality. This can be of interest for i) fuel cell applications and accumulators, ii) selective absorption of gases, and also iii) for coatings of surfaces in which specific binding sites or properties are required. One of the possible applications that we aim at is anion selectivity and binding. This is relevant for instance in the context of waste water treatment. Photo-labile functional groups are also of interest in our molecular cluster compounds. We have shown that alkali metal ions can be easily replaced by Ln2+ ions, yielding isostructural compounds. We intend to include paramagnetic transition metal ions in this study of isomorphous cluster compounds in which metal ions are bridged by phenolate moieties. Upon irradiation, suitable functionalisation will lead to the formation of radicals on the ligand oxygen atom, inducing further paramagnetic centres. We are interested here in the resulting magnetic properties. Another target is the antibacterial properties of our Ag-containing compounds. It is widely known that silver has this antibacterial effect, and even though it was replaced by antibiotics 50 years ago or so, it currently lives a revival because of the increasing resistivity of bacteria against antibiotics. In another project, and in collaboration with microbiologists, dentists and orthopedists, we study our Ag-coordination polymer compounds as coatings for implant biomaterials in order to prevent biofilm formation on these surfaces. However, not much is known about the exact interaction of silver ions with bacteria, their interaction with bacterial cell walls and their interior, if and how silver ion uptake takes place, etc. We therefore intend to also study the interaction of silver ions with biologically relevant molecules, such as peptides. The goal is to find out more about the selectivity of Ag-coordination by the latter. For this second part of the project, we first have to elaborate a screening test for Ag+-fixation with a library of peptides on polymer beads, obtained through collaboration with Helma Wennemers, Basel. First experiments have shown that Ag+-fixation can be screened by reduction of the metal ions with light and the subsequent formation of silver nanoparticles.