NMR Centre of Excellence for Studies in Biotechnology, Pharmacy and Physics of Matter
In the period 2009-13, the NMR Centre of Excellence intends to focus its knowledge and efforts into two primary fields of research, namely, the health and life sciences, and advanced novel synthetic metal and non-metal materials. The consortium consisting of research institutions and highly technologically developed businesses ensures high a quality multidisciplinary team of researchers from academic and business sectors, which combines a critical mass of knowledge and the required research infrastructure to focus on the development of new technologies in our primary research areas.
Nuclear magnetic resonance (NMR) is a spectroscopic method, which enables researchers to make connections between structure, bio-macromolecule sequence, dynamics and molecular recognition, and thus represents a key method for insight into the biological functions, chemical structures and their interactions in liquid and solid states, and the nature of fundamental processes, which are important for production and development of pharmaceutical preparations and new advanced materials. This knowledge opens new biotechnology and biomedicine possibilities, which help to increase competitiveness, to develop an innovative environment, to make progress in medicine and to increase product added value. Research and characterization of new materials for hydrogen storage are in compliance with the world-wide trends of moving towards hydrogen based energy and thus a low-carbon society. Research work is focused on the development of energetically efficient products and thus meeting horizontal goals to stimulate an energetically efficient economy with emphasis on sustainable development.
The Slovenian NMR Centre, in 2000, became the first and the only EU Centre of Excellence in Slovenia. With this title our centre has confirmed its quality and recognition in the highly competitive European science and research arena. This achievement of the NMR centre is based on the strong connections with technologically developed partners in Slovenia, particularly with those from pharmaceutical companies and the chemical industry. The program period 2004-07 contributed to strengthening the role of the NMR Centre of Excellence. We want to continue and expand the long-standing successful partnership with academic institutions and companies in the program period 2009-13. In the framework of the Centre of Excellence we set a goal to achieve a breakthrough and strengthen our position in international collaborations with a vision to contribute to research excellence, development of the research environment, competitiveness and higher added value, transfer of knowledge into companies and thus to the goals of Slovenia in the priority areas of research and technological development by combining the critical mass of knowledge. Strategic goals of partners involve deepening of cooperation in the framework of 16 R&D projects, better utilization of the capacities of our NMR centre and further development of research infrastructure, which will enable us to meet the set goals.
- National Institute of Chemistry, Ljubljana
- Jožef Stefan Institute, Ljubljana
- Faculty of Chemistry and Chemical Technology, University of Ljubljana
- Krka, d.d., Novo mesto
- Lek Pharmaceuticals d.d., Ljubljana
- Betonal d.o.o. Trebnje
- OptaCore d.o.o. Ljubljana
- Jeklotehna TEHO d.o.o., Ljubljana
Coordinator of projects: Janez Plavec
RRP1: Solid-state nuclear magnetic resonance and studies of polymorphism
Within the project we shall study polymorphism in the field of pharmacy and investigate mesoporous silicate drug-delivery systems and interactions of the active substances with either drug-carriers or excipients. In addition to more established techniques, we shall extensively use high-resolution solid-state NMR spectroscopy and ab-initio calculations of NMR- detectable parameters.
RRP2: Structure and analysis of organic compounds in solution with the use of NMR
The majority of medically active ingredients that are in clinical use today represent small organic molecules. During the synthesis, side products are produced in addition to the desired compound. Modern NMR methods have become one of the main tools of their qualitative and quantitative determination.
RRP 3: Characterization of recombinant proteins and biological macromolecules in aqueous solution
Our main interest is focused on proteins, mostly from human, involved in vital cellular processes with respect to their potential medical applications. The NMR spectroscopy enables us to obtain information about protein structure in solution at nearly in vivo conditions taking into account temperature, ionic strength, pH, chemical modifications and binding of different substrates. In additionally, we apply modern NMR techniques to obtain valuable information about molecular dynamics in protein, protein-protein, protein-DNA/RNA complexes in solution.
RRP 4: Interactions of new ligands with protein targets, rational drug design
The formation of ligand-receptor complexes will be investigated by NMR methods, which enable identification and characterization of intermolecular interactions. A unique structural-dynamic insight into the differences in biological activity of novel ligands will be provided, which can significantly upgrade the drug design studies based solely on the rigid crystal structures.
RRP 5: Synthetic biology
Synthetic biology represents an emerging approach to solve important problems combining engineering approaches with biological sciences. We will investigate molecular mechanism of innate immune response as the first line of defence to develop new therapeutic strategies based on the structural insight and principles of synthetic biology.
RRP 6: Asymmetric synthesis: Development of new chiral ligands for metal-promoted asymmetric transformations
We are active in asymmetric catalysis which is based on the use of metal-organic catalysts to access chiral molecules. Our focus is the preparation and development of our own proprietary ligands and catalysts for industrial applications, for example in hydrogenation and transfer hydrogenation. Chiral nitrogen and phosphorus containing ligands are being developed in our laboratory.
RRP 7: Qualitative and quantitative analysis of organic compounds with hyphenated techniques
For qualitative and quantitative chemical analysis in the fields of pharmacy, environmental protection, clinical chemistry, biochemistry etc. we will develop methods based on hyphenated techniques, i.e. chromatographic techniques (LC, GC, TLC) coupled with spectroscopic (UV/VIS, MS, NMR) techniques, which predominate in the modern analytics of organic compounds.
RRP 8: Vibrational spectroscopy of drugs and auxiliary substances
The main objective of the project is development of the methodology for application of vibrational spectroscopy (infrared, Raman, VCD and IRRAS) for structural studies of drugs and auxiliary molecules. These studies will be extended by implementation of modern techniques of vibrational spectroscopy for studying molecular interactions, drug encapsulation and delivery.
RRP 9: Nuclear quantum effects in enzymes, receptors and hydrogen bonded systems
We study dynamics of proton transfer processes in small hydrogen bonded systems, enzymes and receptors. Our computational work is augmented with NMR spectroscopy, vibrational spectroscopy and pharmacological testing. Our research provides new insights into the nature of enzyme catalysis and receptor triggering with drug design is a direct application.
RRP 10: Study of drug delivery systems based on polymeric carriers
The project is focused on structural characterization of polymeric drug delivery carriers such as amphiphilic copolymers, hyperbranched polymers and dendrimers. We will study structural characteristics of conjugates in which the low molar mass drugs are covalently bounded to polymeric carriers. In the case of complexes we will investigate non-covalent interactions between the drug and polymer.
RRP 11: Compounds for diagnostics and medical therapy
The toolbox of modern synthetic organic chemistry, such as transition metal catalyzed C-C bond formation, direct arylation via C-H bond activation, and metathesis, will be utilized for the preparation of novel compounds directed towards new or improved molecular probes and drugs for medical application.
RRP 12: Biologically active coordination compounds – synthesis, structure and properties
Synthesis of complexes of natural antioxidants, zinc and cobalt complexes as model compounds for metalloenzymes, and novel biologically active ruthenium complexes, their precise structural characterization in the solid state using X-ray diffraction and in solution using NMR spectroscopy, the assessment of the potential use of isolated compounds for therapeutic purposes.
RRP 13: Nuclear magnetic resonance of new "smart" materials
The aim of the projects is to develop, synthesize and explore new metals-based materials that show "smart" physical properties like the combination of high electrical conductivity with low thermal conductivity, the combination of hardness, elasticity and low friction coefficient, high hydrogen storage capacity and the thermal memory effect for thermal inscription of digital information by pure temperature manipulation.
RRP 14: Hydrogen energy - Towards low-carbon society
The aim of the research is to develop and synthesize novel metals-based materials for hydrogen storage, including quasicrystals, complex metallic alloys, bulk metallic glasses and nanoparticles. Multicomponent alloys from chemical elements Ti, Zr, Ni, Al, Cu, Pd and Pt will be investigated for high hydrogen storage capacity, high hydrogen mobility and easy loading and unloading.
RRP 15: Magnetic resonance imaging
MRI project group conducts basic science research in development of new MR imaging methods as well as in the following applicative fields: MRI in development of new controlled-release, MRI in monitoring of food preparation, production and storage. In addition the group provides educational and instrumental services for potential users.
RRP 16: NMR probe development for the research of complex materials with simultaneous ferroelectric, ferromagnetic or ferroelastic properties
We are developing an enhanced functionality NMR probe, which will be capable of applying RF magnetic fields, as conventional probes do, simultaneously with: static electric fields, illumination, and strain. All this functionality is required to study the technologically promising multiferroic materials, which exhibit simultaneous ferroelectric, ferromagnetic and/or ferroelastic properties.