Research fields involving volatile compounds: from sniffing dogs to modern mass spectrometric analytical techniques

A. Amann ^1,2

¹Breath Research Institute, Austrian Academy of Sciences, Dammstr 22, A-6850 Dornbirn

²Univ.-Clinic for Anesthesia, Innsbruck Medical University, Anichstr 35, A-6020 Innsbruck

The analytical methods for detection of volatile compounds have been greatly improved during the last decade. This is, in particular, so for direct mass spectrometric methods such as proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF) [1]or for portable instrumentation like ion mobility spectrometry (IMS).

Various different fields of research make use of volatile compounds:

• Exhaled breath analysis for diagnosis and therapeutic monitoring [2]
• Simulation of hemodynamics and lung mechanics [3]
• Headspace analysis for cell and bacterial cultures [4]
• Headspace analysis of urine
• Urban search and rescue operations using gas-analytical methods for detection of compounds released by entrapped victims (after, e.g., earthquakes) through breath, urine or sweat.

The prototype and paradigm of such investigations are dogs with their highly developed olfactory capabilities. Dogs are used in search and rescue operations [5]and are even said to be able to detect certain diseases (e.g. cancer) based on volatile compounds released by patients or volunteers. On the other hand, dogs can easily be distracted, get stressed, or even frustrated. Therefore, a huge demand exists for portable instruments, which could complement, or even replace their work. Analytical instrumentation with the same real-time capabilities as dogs would be an enormous progress and highly desirable.

Portable hand-held devices would be particularly interesting for medical applications in clinical routine. Even though some devices exist (such as a hand-held device for nitric oxide measurement in exhaled breath for asthma monitoring), research on volatile compounds released by the human body is still in its infancy. For most compounds we do not even have information about their biochemical background. For the elucidation of the biochemical origin of volatiles, cell and bacterial cultures may serve as tools [4]. The concentration of precursor compounds in the culture medium may be changed and isotopically labeled precursor compounds may be used.

References

1. J. Herbig at al., J Breath Res 3 (2009) 027004.
2. A. Bajtarevic et al., BMC Cancer 9 (2009) 348.
3. J. King et al., Physiol Meas 31 (2010) 1169.
4. W. Filipiak et al., Cancer Epidemiol Biomarkers Prev 19 (2010) 182.
5. A. Ferworn, Canine augmentation technology for Urban Search and Rescue, in Canine Ergonomics: The Science of Working Dogs, W. S. Helton, Editor. 2009, CRC Press: Boca Raton. p. 205

How to copy nature? Is it possible to build cell membrane inside chromatographic column?

Bogusław Buszewski, Szymon Bocian

Chair of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University, Torun, Poland

The separation techniqies, especially high performance liquid chromatography (HPLC) is one of the commonly used for analytes separation in pharmaceutical, medical and environmental analysis. Because of that fact, for analysis of bioactive substances the new specific stationary phases are necessary. Scientist are looking for materials which may be dedicated for separations of peptides, aminoacids and hormones. Other tendency observed is to imitate the structure of cell membrane inside chromatographic column.

There are know stationary phases which contains specific polar groups inside bonded ligands, e.g. amino, amide ect. or materials which contains immobilized cholesterol molecule. These materials may be an alternative solution for analysis of bioactive compounds with different polarity. It also allows modeling the transport of a given compound through the membrane.

From the biomedical and pharmaceutical point of view there is one material which can imitate the cell membrane in chromatographic system. It is Immobilized Artificial Membrane (IAM stationary phase). It can be used for new drugs to model their interactions with cell membrane.

Another aspects in preparation materials which can copy the nature are the monolithic stationary phases for liquid chromatography and other separation techniques. The porous structures of these materials imitate the structure of the rock and exhibit excellent mass transfer during separation in liquid chromatography. It can be also used as a support for modifications in the chemically bonded stationary phase synthesis procedure.

How and why brain-computer interfaces spy on our intentions

P.J. Durka

University of Warsaw, Faculty of Physics, Hoża 69, 00-681 Warsaw, Poland

There are ~10¹² neurons in the brain, each of them making up to 10⁴ connections with the others. Electrical impulses carried by these connections sum up at the receiving neurons, eventually causing them to fire up, and send another impulse. Even with the dramatically oversimplified binary model of neurons operation, any approximate count of different possible connection schemes is huge, compared e.g. to the number of protons in the Universe or its age. That should humble our declarations about cracking the neural code, especially given that to decode the workings of the brain we have no better tool than the brain itself.

In spite of that, nowadays brain-computer interfaces (BCIs) have definitely moved from the domain of science-fiction (Matrix, Avatar, Surrogates, Spiderman 2...) into the scientific laboratories, and today we are working on the transfer of this technology to the bedsides of the most needing patients [1]. BCIs may be the only way of contacting the world for people suffering from neurodegenerative diseases like ALS, and a great help in multitude of less severe cases, like that of the author of the book The Diving Bell and the Butterfly.

By definition, BCI is a system which allows controlling physically the external world without using any muscular activity, that is only by thoughts. How is that possible without mind-reading will be briefly explained during the lecture; we shall present the state of the art worldwide and recent achievements in Poland. We will concentrate on the most practical BCIs based on the traces of the brain's electrical activity which can be read from the skull. This signal is called electroencephalogram (EEG). The two simpler approaches are based on evoked potentials (P300 and SSVEP), which exhibit the neural correlates of selective attention, and hence require the user to concentrate on flashing symbols. The more natural paradigm relies on motor imagery: EEG traces of imagination of the left hand movement can be translated into the command to turn left. However, such systems require much more complicated signal processing and extensive training of the user.

References

1. OpenBCI project, University of Warsaw, website http://openbci.pl

 

Libyan Desert Glass – Mystery and Challenge

G. H. Frischat

Institut für Nichtmetallische Werkstoffe, Technische Universität Clausthal, Zehntnerstraße 2a, 38678 Clausthal-Zellerfeld, Germany

Libyan Desert Glass (LDG), a natural glass, is found in the southwest of Egypt near the Libyan border. Its strewn field has an area of about 3500 km2. LDG is unique compared to other natural glasses since it consists of > 97 % SiO2 together with the oxides of Al, Fe, Ti, Zr, Ca, Mg and some further traces, e. g. Mn, Na, K, rare earths, Th and U. It is interesting to note that in some samples of LDG siderophile elements such as Co, Ni, Ir were detected. The mean age of LDG was determined to be 28.5 x 106 years. LDG pieces found today have dimensions between several mm and > 300 mm. Some specimens have a faint green tint, are bubble free and homogeneous; other pieces are greenish yellow and less homogeneous and contain bubbles and/or dark streaks with Fe2O3 enrichments and inclusions of traces of crystals indicating high temperature and in some cases also a high pressure event during formation of the glasses. However, there are also reports on possible organic inclusions such as sporomorphs, pollen grains and debris of chitine.

It is not only now that LDG had attracted interest. There is evidence that already in neolithic times artefacts of LDG were used as tools such as knives and it is fascinating to learn that a piece of greenish coloured LDG formed the scarab in the pectoral of the Egyptian Pharaoh Tutenkhamun (1347 – 1338 BC). The origin of LDG is still a matter of debate. Both terrestrial and extra-terrestrial origins have been suggested and high and low temperature formation processes also.

This presentation first reports on some known properties of this natural glass and then it focuses on a critical discussion of the different formative hypotheses. However, Libyan Desert Glass still remains a mystery and a challenge.

Nanomaterials and their application in Biomedicine

Michael Giersig

Department Physics, Experimental Physics Institute, Arnimallee 14,14195 Berlin, Germany

giersig@physik.fu-berlin.de

Abstract

Nanotechnology applied to biology requires a thorough understanding of how molecules, sub-cellular entities, cells, tissues and organs function and how they are structured. The merging of nanomaterials and life science into hybrids of controlled organization and function is possible, assuming that “biology is nanostructured”, and therefore man-made nano-materials can structurally mimic nature and complement each other. By taking advantage of their special properties, nanomaterials can stimulate, respond to and interact with target cells and tissues in controlled ways to induce desired physiological responses with a minimum of undesirable effects. To fulfill this goal the fabrication of nano-engineered materials and devices has to consider the design of natural systems. Thus, engineered micro-nano-featured systems can be applied to biology and biomedicine to enable new functionalities and new devices. These include, among others, nanostructured implants providing many advantages over existing, conventional ones, nanodevices for cell manipulation, and nanosensors that would provide reliable information on biological processes and functions.

Biography

Michael Giersig recieved his PhD in chemistry at the Freie University and Fritz Haber Institute of Berlin in 1988. In 1995 he was awarded an international accolade of a 2-year stay at the University of Melbourne. He then habilitated at the University of Potsdam in 1999. In 2003, Michael Giersig joined the Center of Advanced European Studies and Research (Caesar)) in Bonn, to establish the group “nanoparticle technology”. He was appointed professor at the University of Bonn in 2005 and awarded a Fulbright scholarship for a 6 month research stay at the Boston College and Harvard Medical School 2005/2006. Also in 2006 Giersig obtained the title "Professor of Physical Science" from the President of the Republic of Poland. In 2007 he received a First Degree Medal for outstanding contribution to the development of the Faculty of Nuclear Sciences and Physical Engineering the Czech Technical University in Prague. Finally, last year he was invited to Beijing as a Visiting Professor at the Chinese Acadamy of Sciences. The goals of Professor Michael Giersig’s research at FU Berlin science May 2009, lie in the preparation of nanometer-sized semiconductor, metallic, and magnetic particles, followed by the creation of periodically ordered nanostructures (1-D, 3-D) based on single nanoparticles. A small particle size implies high sensitivity and selectivity. These new effects and possibilities are mainly due to quantum effects that are a result of the increasing ratio of surface to volume atoms in low-dimensional systems. An important factor in this context so far has been the design and fabrication of nanocomponents with/displaying new functionalities and characteristics for the improvement of existing materials; including photonic materials, conductive materials, polymers and composites. With this concept of nanotechnology in mind, Giersig aims at developing innovative products and application options in electronics and biomedicine, based solely on nanoscale technology.

Fascination with the sky: from Hevelius to modern astrophysical computer simulations

Michał Hanasz

Centre for Astronomy, Nicolaus Copernicus University

ul. Gagarina 11, PL-87-100 Toruń, Poland

Observations of the sky fascinated people all over the history of human civilisation.

A spectacular step forward in understanding of the Universe has been made by XVIIth century astronomers - Galileo who invented first telescopes for astronomical observations, Johannes Kepler and Johannes Hevelius, who constructed the biggest telescopes of his times, including a large telescope of 45 m focal length. The observations performed by these astronomersprovided foundations for Isaac Newton's theory of universal gravitation.

On the other hand, the contemporary toolbox of astrophysicists includes numerical simulation techniques aimed at computer modelling of the Universe. I am going to talk about the most spectacular numerical simulations of the formation of cosmological structures, galaxies, stars and planets. The numerical simulation techniques make it possible to experiment with astrophysical objects, and to imitate Nature on the cosmic scales in computer laboratory.

Granular Mechanics in the Geophysical and Geotechnical Context

An Interplay between Order and Chaos

Kolumban Hutter

Prof. em. Darmstadt University of Technology, c/o Versuchsanstalt für Wasserbau, Hydrologie und Glaziologie, ETHZ , Goriastrasse 37, 8092 Zurich. hutter@vaw.baug.ethz.ch

Granular materials at rest and in motion exhibit surprisingly complex behaviour. Under static conditions their macro-thermo-mechanical response largely depends on the micro-structure and the bonds and forces between their elements.

A sponge is a porous solid body whose behaviour critically depends on the pore space and the amount of liquid and gas in this pore space. It can completely or partly fill the latter, thus giving rise to the complex mechanical behaviour of saturated or unsaturated materials with limited compressibility when dry but gigantic compact-ability when being wet.

Clay, silt and sand as porous bodies have little to none cohesion; owing to their granular structure they behave differently under compression, tension and shearing deformation and, depending upon the external loading, their mechanical response is akin to that of a solid, fluid or a gas. In a sand heap the size and orientation orderings often appear to be unstructured, but when focussing at the dimensions of the granules’ micro-scale of particle size and particle orientation, structured distributions are often discernible. In avalanching motions these structures are destroyed, but, depending on the fluid dynamical details of this motion, the motions either lead to chaotic or completely newly structured depositions.

This behaviour exerts its influence in various branches of the sciences. Geotechnical engineers and engineering geologists must base their soil structural analyses on soil mechanical models, which account for the formation of shear bands, liquefaction phenomena, etc., to find limit load concepts, which avoid such ’instabilities’ and the ensuing catastrophic landslides, all too often seen during excessive flood events in mountainous regions or in sudden collapses of shores at reservoirs of former strip mining excavations. Or they need to develop models to forecast or re-analyse the release, motion, trim-lines and travel distances of such catastrophic granular flows. Structural geologists, on the other hand, can reconstruct possible events from the architecture of the sand depositions and thus interpret the past evolution of certain alluvial processes.

After briefly touching geophysical examples of dense granular and particle laden flows, descriptive features of granular materials are discussed: (i) dilatancy, (ii) the role of the interstitial fluid, (iii) solid, fluid and gas-like behavior, (iv) fluidization and (v) particle size segregation. Table top experiments will underline the discussed behaviors.

Sustainability and Clean Technology - a Challenge for Chemists and Engineers

A.A.F. Kettrup

Technical University Munich, Center of Life and Food Sciences, Dept. Environmental

Analytical Chemistry, Weihenstephaner Steig 23, D-85350 Freising/Germany

In the past industry has developed chemical products and has optimized the production process as well as the product quality, looking for the best suitable properties in different application fields.

Now, ideas of environmental prevention are rising. On the one hand we are looking for the reduction of materials flow, that means for avoidance or minimization of waste and, especially in case of polymers, for recycling or down cycling of materials.

On the other hand, it is necessary to follow the idea of clean technology, that means of product and process integrated environmental protection. So, products and processes should be developed which are safer and more tolerant regarding the environment and it’s organisms. Several joined projects with the industry have been performed for the developing of safer products and processes, e.g. together with Siemens AG the development of halogen free flame retarded polymers. We developed the new materials to avoid, in case of burning, the formation of brominated dioxins and furans.

Furthermore we simulated the combustion process and investigated the emissions by ecotoxicological test systems.

How nano-hairs (nano-whiskers) grow and what they are useful for?

Grzegorz Karczewski

Institute of Physics, Polish Academy of Sciences, Warsaw, Poland.

One-dimensional (1D) semiconductor nanostructures (called nano-whiskers) very much resemble human or animal hairs. However, nano-whiskers (NWs) are about 10 000 times thinner and shorter that hairs of the living species. They exhibit unique physical properties which makes them interesting from the point of view of potential applications. For instance, NWs offer new possibilities in electronic device architecture and functionalities. The first part of the presentation will be devoted to review contemporary and future applications of NWs in nano-electronics, nano-photonics, biology etc. In particular, their role as very versatile building blocks in the so-called “bottom–up” approach in the device engineering will be shown and discussed.

Further, the presentation will sketch technological methods employed to grow nano-whiskers and show their morphology and physical properties. Nano-whiskers (NWs), with typical diameters in the range of 5-30 nm and lengths of up to several micrometers are typically grown on planar substrates with metal catalyst nano-particles deposited prior to the NW growth. The catalytic nano-particles (most often gold) induce the NW growth by vapor-liquid-solid mechanism, in which the NW grows under the catalytic particle. Scanning and transmission electron microscopy (SEM and TEM) reveal the presence of nano-whiskers with densities, diameters and lengths strongly dependent on growth time and growth conditions. By both TEM and SEM, the hemispherical Au-rich seeds are clearly visible at the tip of nano-whiskers.

Discoveries by Transmission Electron Microscopy

¹L. Kienle, ²V. Duppel, ¹A. Lotnyk, ¹U. Schürmann, ¹V. Hrkac, ¹B. Erkartal, ³B. Mogwitz, ³J. Janek, ²A. Simon

¹. Faculty of Engineering, Institute for Materials Science, Christian-Albrechts- University Kiel, Kaiserstr. 2, D-24143 Kiel, Germany. lk@tf.uni-kiel.de

². Max Planck Institute for Solid State Research, Heisenbergstr. 1, D-70569 Stuttgart, Germany

³. Institute of Physical Chemistry, Justus-Liebig-University, Heinrich-Buff-Ring 58, 35392 Gießen, Germany

Transmission electron microscopy (TEM) techniques are of paramount importance for performing structural and chemical analyses of small objects and marginal sample quantities. In this regard, all standard methods are likely to fail due to insufficient sensitivity and space averaging. Hence, TEM enables the discovery of frequently overlooked, but essential aspects of synthetic solids and minerals. Our fundamental research on lanthanide-rich carbide iodides and carbide nitride iodides [1] contains well documented examples. In this case, TEM examinations enabled us to identify and analyze an unexpected plethora of lamellar and complex intergrowth phases with new components.

Recently, we extended our real structure observations to functional bulk materials and thin films within the frame of the funding priority Kiel Nano Sciences. The materials of interest are e.g., thermoelectrics and phase change materials based on complex tellurides [2], intelligent multi-layer materials for biomagnetic sensing, and ferromagnetic shape memory alloys for sensors and actuators [3]. A common motif of the research deals with the interrelation of syntheses, real structures, and the properties of the materials. For instance, sphalerite-type semiconductors show a complicated scenario of local ordering of atoms and structural vacancies which can be extended into periodic nanostructures by well defined strategies for the syntheses, including VLS (Vapor Liquid Solid) growth. Nanodisperse noble metal semiconductors, like thin films of Ag-doped silver selenide, are well known for their linear and non-saturating magneto-resistance (MR) and the surprisingly large influence of the synthesis conditions on the MR effects and the real structure. The optimum parameters for achieving linear MR effects by post-annealing could be fixed by combining TEM and MR measurements. Via rapid quenching of Ag₂Se bulk samples we obtained a separation of two polymorphs with discernable morphology. Rapid quenching also enabled us to prepare bulk crystals of Au-doped Ag₃AuTe₂, the first ternary system with linear MR. The material represents a new type of linear MR material. In contrast to Ag-doped silver selenide with the Ag-nanoclusters dispersed in a chemically homogeneous matrix of Ag₂Se, the particles of Au-doped Ag₃AuTe₂ are composed of submicron sized grains of an inhomogeneous matrix material.

References

1. M. C. Schaloske, L. Kienle, Hj. Mattausch, V. Duppel, A. Simon, Europ. J. Inorg. Chem. accepted 2011
2. U. Schürmann, V. Duppel, S. Buller, W. Bensch, L. Kienle, Cryst. Res. Technol., in press 2011
3. C. Bechtold, J. Buschbeck, A. Lotnyk, B. Erkartal, S. Hamann, C. Zamponi, L. Schultz, A. Ludwig, L. Kienle, S. Faehler, E. Quandt, Adv. Mater., 22, 2668 (2010)
4. L. Kienle, V. Duppel, B. Mogwitz, J. Janek, M. v. Kreutzbruck, A. Leineweber, A. Simon, Cryst. Growth Design, accepted 2011

Fiat Lux: The Development of Lightning Technology

H.-Jürgen Meyer

University of Tübingen, Abteilung für Festkörperchemie und Theoretische Anorganische Chemie, Auf der Morgenstelle 18, 72076 Tübingen, Germany

Light has been an essential source of human life since ever, bringing along warmth. The importance of light for mankind is out of question has been expressed in the book of Genesis 1,3: "dixitque Deus fiat lux et facta est lux" ("and God said let there be light, and there was light"). Today the old latin words lux and candela are common measures of modern light technique.
The technology of generation of visible light has changed considerably during the past centuries, and today we focus the end of the light bulb as a general light source in favour of more energy efficient lightning sources.¹
After the fundamental development of the blue (In_1-xGa_xN) light emitting diode (LED) by Shuji Nakamura at the beginning of the 1990ies a new age of light emitting radiation converters began. Besides the well-know garnet materials (YAG) new alkali-earth and rare-earth based nitridic materials have become attractive for the generation of white light.
The design and synthesis of these new materials may be accomplished by classical solid state or by solid state metathesis reactions²; the latter being developed in our laboratory for complex nitridic compounds. Examples of novel radiation converters may be based on boronitride³, carbonitride⁴, carbon-nitride derivatives⁵, cyanamidosilicate⁶, cyanamidoaluminate, and nitridosilicate⁷ compounds. Crystal structures and luminescence properties of materials and their application in LED technique are presented.

References

1. M. Born, T. Jüstel, Chem. Unserer Zeit 40 (2006) 294.
2. H.-J. Meyer, Dalton Trans. 39 (2010) 5973.
3. B. Blaschkowski, H. Jing, H.-J. Meyer, Angew. Chem., Engl. Ed. 41 (2002) 3322.
4. M. Neukirch, S. Tragl, H.-J. Meyer, Inorg. Chem. 45 (2006) 8188; J. Glaser, L. Unverfehrt, H. Bettentrup, G. Heymann, H. Huppertz, T. Jüstel, H.-J. Meyer, Inorg. Chem. 47 (2008) 10455.
5. S. Tragl, K. Gibson, J. Glaser, V. Duppel, A. Simon, H.-J. Meyer, Solid State Comm. 141 (2007) 529.
6. J. Glaser, H.-J. Meyer, Angew. Chem., Engl. Ed. 47 (2008) 7547; J. Glaser, H. Bettentrup, T. Jüstel, H.-J. Meyer, Inorg. Chem. 49 (2010) 2954.
7. H. A. Höppe, H. Lutz, P. Morys, W. Schnick, A. Seilmacher, J. Chem. Phys. Solids 61 (2000) 2001; K. Uheda, N. Hirosaki, H. Yamamoto, Phys. Stat. Sol. A 203 (2006) 2712.

Transfer of organic matter and associated trace metals in benthic food web of the Gulf of Gdańsk

Sokołowski A¹., Wolowicz M¹., Richard P.²

¹University of Gdansk, Institute of Oceanography, Al. Pilsudskiego 46, 81-378 Gdynia, Poland

²Littoral, Environnement et Sociétés, UMR 6250 CNRS-Université de La Rochelle, Bât. Marie Curie, Avenue Michel Crépeau, 17042 La Rochelle, France

Large spatial asynchrony of hydro-geological parameters, resident macrobenthic communities and anthropogenic metal contamination make the ecosystem of the Gulf of Gdańsk a good environment in which to study food web structure and trophic transfer of trace metals. Combined measurements of naturally occurring isotopes of carbon and nitrogen showed that the baseline of the food webs is suspended organic matter, of which autochthonous phytoplankton serves as the main organic matter source, and sediment organic matter. Analyses of the δ¹³C and δ¹⁵N in abiotic compartments and macrobenthic organisms revealed a relatively simple structure of benthic food web with to a maximum of three to four trophic levels (RTL). The share of species is primarily clustered at the second trophic level (primary consumers) with a decreasing trend towards higher consumers that agrees with the classical food web theory. Rough proxy of carbon partitioning among trophic levels, using estimates of macrobenthic biomass (gC m^-2), demonstrated a conventional scheme of trophic structure in all regions of the Gulf. Primary consumers generally acquired most carbon with a steep slope to the secondary consumers. The pattern depicts diminishing amount of energy available to support each subsequent trophic level probably due to limited efficiency of energy transfer (trophic efficiency) that ranges from 0.1% to 30.4%. Stable nitrogen isotope ratio coupled with concurrent measurements of bioavailable fractions of metals (Cu, Fe, Mn, Zn) in the environment and accumulated metal concentrations in organisms allowed quantifying metal transfer in the benthic food web. Mathematical models estimating the trophic transfer dynamics varied between elements. Iron and Mn concentration decreases in successive trophic levels as a function of trophic position owing to interspecies differences in metal handling strategy. Biotransformation processes of Fe and Mn in higher-trophic-level organisms presumably include lower ingestion rate, less efficient assimilation related to less selective feeding and efficient efflux. Large tissue mass of higher consumers (particularly fish), that increases disproportionably faster than metal accumulation from food, can possess a “diluting effect” on metal burdens. Mean biodiminution rates were 3.0 fold and of 2.3 fold, for Fe and Zn, respectively. Copper and Zn revealed a similar two-phasic pattern, including an increase in metal concentrations between food sources and primary consumers followed by a decrease in higher trophic levels. Effective assimilation of metal from food coupled with slow efflux out of a body are presumed to account for biomagnification of the elements within the lower trophic levels. Biodiminution between higher trophic levels is admittedly related to physiological resistance to environmental metal concentrations, internal control of uptake and regulation of the total body metal concentration. Considering the entire food web, Zn tends to amplify by a factor of 1.2 while no trophic transfer of Cu has been detected.

Similarities and Differences in Small Molecule Drug Design

H. Stark

Goethe University, Institute of Pharmaceutical Chemistry, Biozentrum, ZAFES/NeFF/OSF, Max-von-Laue-Str. 9, D-69438 Frankfurt/Main, Germany

Drug design in pharmaceutical / medicinal chemistry has to consider numerous possibilities of ligand interactions at a molecular level mainly with the target protein. These interactions responsible for the molecular recognition are mainly reversible non-covalent bindings of low energy. Therefore, it is difficult to find the best starting point for drug development (lead structure) that within a few years should result in a therapeutically useful drug. The initial steps in finding a lead structure for further optimization is frequently based on the knowledge of the endogenous ligand or in a non-rational way on high through-put screening.

Since endogenous ligands commonly have promiscuous properties on a target family, i.e. different receptor subtypes, the chemical structure should have on the one hand some structural similarities to hit one target but on the other hand display enough discrepancies in structural overlay to avoid the activation of some structurally related (non-)targets. Bioisosterism is one approach to compounds with high affinity and high selectivity that the potential biologically active drug has reduced unwanted side effects. Recognition or missing of recognition of chemical functionalities are essential elements for successful drug development. Despite the fact that the former approach on “one disease – one target” has been overcome, the pharmacological profiling of compounds on a number of targets as well as missing affinity on non-targets based on their structural variations.

With examples on ligand development at histamine receptor subtypes possibilities and limitation on some approaches on structural likenesses, drug likeness and structural differences will be described.

Spying on biological systems – Perspectives of synthetic biology

Henning Steinicke¹, Jörg Hacker¹ & Bärbel Friedrich²

¹Deutsche Akademie der Naturforscher Leopoldina – National Academy of Sciences

²Humboldt-Universität zu Berlin, Institute of Biology, Dept. General Microbiology

During the last years synthetic biology has developed as a highly interdisciplinary research area at the intersection of molecular biology, organic chemistry, engineering sciences, and nano-biotechnology. The focus of synthetic biology is to generate biological systems that have no counterpart in nature. The technology driven concept includes aspects of chemically synthesised nucleic acids, generation of artificial peptides, complete genome synthesis, transplantation and minimisation of genomes, as well as the generation of synthetic regulatory networks, production of novel drugs, biopolymers and fuels. In addition, a future vision aims at the construction of bio-hybrid systems, so-called protocells, that mimic "life-like" processes.

Synthetic biology builds the bridge between analysing and modifying biological systems on the one hand and synthesis and construction of bio-inspired systems on the other hand. The range of possible applications of synthetic biology is wide and covers among other products also renewable energy carriers. Facing a globally rising demand for energy, while fossil resources become limited, synthetic biology opens innovative routes of future energy supply. Sustainable production of hydrogen, although still at an experimental level, is one most promising example for a low-carbon energy future. The concept involves a water splitting catalyst powered by sunlight, e.g. the microbial photosystem, and an efficient proton reducing catalyst such as hydrogenase. The biological systems provide a blue print for the construction of bio-inspired chemical catalysts that are subject of on-going research.

References

1. German Research Foundation, German Academy of Science and Engineering, and German Academy of Sciences Leopoldina – National Academy of Sciences (2009): Synthetic Biology – Statement. Wiley-VCH, Weinheim: 96 pp.
2. Hartwell, L.H, J.J. Hopfield, S. Leibler, and A.W. Murray (1999): From molecular to modular cell biology. Nature 402: C47-C52.

On the Notion of Symmetry, or How Mathematics Attempts to Describe Reality

A. Strasburger

Warsaw University of Life Sciences - SGGW, Faculty of Applied Informatics and Mathematics, ul. Nowoursynowska 159, 02-776Warsaw, Poland

An intuitive conception of symmetry is one of the very basic building blocks of our perception of real world. It derives from a great number of phenomena of nature - from the shapes of living animals to the amazing crystalline structures of minerals. It marks also its strong presence in the development of various activities of the mankind from its early history – architecture, visual decorative arts and nowadays even in the industrial design. And although it was dismissed by one of the gurus of the modern art as "an aesthetic of the fool"', symmetry continues to be present in modern art.

It is therefore not at all astonishing that the concept of symmetry makes its appearance in the abstract world of mathematics. From its mystical beginnings related with the harmony of numbers studied by Pythagoreans or with the basic elements of the Universe by Plato, it has developed into a very powerful tool of modern mathematics – the theory of groups. More amazingly perhaps, the notion of symmetry emerged to be an underlying principle of modern physical theories searching for understanding of the fundamental laws governing the world - `Am Anfang war die Symmetrie' says Werner Heisenberg. Many of those fundamental laws turned out to be nothing else then the manifestations of various symmetries of the physical world – a classical and widely known example being the Minkowski's formulation of Einstein's special relativity in terms of symmetries of space-time.

In this talk I shall attempt to present the basic manifestations of symmetry in the natural and constructed world and to describe the way it was transformed into the mathematical notion of an "abstract"' group. I shall also devote a few words to another concept arising from symmetry manifestations in nature – the fractal geometry.

References

1. P. Yale, Geometry and Symmetry, Dover Publ. 2004.
2. H. Weyl, Symetria, Warszawa, 1960.
3. 3. E. Wigner, Comm. Pure and Appl. Math., 13, 1 (1960).

   
Drug development - how can we imitate gastrointestinal tract for testing tablets and capsules

M. Sznitowska

Medical University of Gdansk, Department of Pharmaceutical Technology, ul. Hallera 107, 80-416 Gdansk, Poland

Drug substances administered in tablets or capsules must undergo dissolution in the gastric or intestinal fluids of the gastrointestinal tract before they can be absorbed and reach the systemic circulation. Therefore, dissolution is a critical part of the drug-delivery process. Measuring the drug concentrations in the blood (in vivo bioavaliability studies) is the best way to prove that release of the drug from the formulation and further drug absorption takes place. However the costs of in vivo study are high and can not be employed on a routine basis. These difficulties have led to the introduction of official ‘in-vitro’ tests.

Dissolution (release) test is a standardised method for measuring the rate of drug release from a tablet or capsule to an acceptor fluid which is most frequently hydrochloric acid (pH 1.2), phosphate buffer (pH 6,8-7,4) or water. This simple test serves very well in the drug development stage when optimisation of the formulation and stability assessment is a goal. When the pharmaceutical product is already on the market the test is performed as a routine assessment of production quality and uniformity between production lots.

When manufacturer aims to demonstrate in vitro, without in vivo bioavailability study, that generic product performs as the one already on the market, such simple dissolution test is generally insufficient and in many cases in vivo bioavailability test is required. However, the possibility of substituting dissolution tests for clinical studies has been revealed by development of “biorelevant” conditions of the test. Current dissolution testing takes advantage of the extensive physiologic information that is available, such as buffer species, pH, bile salts, gastric emptying rate, intestinal motility, and hydrodynamics. Bio-relevant media used in the tests represent gastric and intestinal environment in fasted and fed states and design of apparatus allows to simulate hydrodynamics and mechanical stress that the tablet is subjected to when administered orally.

As in vitro methods advance in their physiological relevance, better in vitro-in vivo correlations will be possible. This will, in turn, lead to in vitro systems that can be utilized to more effectively design dosage forms that have improved and more consistent oral bio-performance.

References

1. A J.B. Dressman, G.L. Amidon, C. Reppas, V.P. Shah, Pharm. Res. 15 (1998) 11.
2. Q. Wang, N. Fotaki, Y. Mao, Dissol. Technol. 16, 3 (2009) 6.
3. G. Garbacz, S. Klein, W. Weitschies, Exp. Opin. Drug Deliv. 7 (2010) 1251.

Can we determine a biological role for anything?

G. W. Węgrzyn

University of Gdańsk, Department of Molecular Biology, Kładki 24, 80-822 Gdańsk, Poland

The question about a biological role for certain cells, tissues, organs or either biochemical or physiological processes has been asked for many times. It is a temptation for biologists to try to understand particular role or target of any piece of a biological entity or a process occurring in the body or in a population. This leads to an assumption that there is a particular aim in biological processes. On the other hand, looking at the history of biological research, and particularly, considering mechanisms of biological evolution, one may ask a question whether it is possible to determine a biological role for anything? Undoubtedly, we are able to understand mechanisms of certain biological processes, however, looking for specific role or aim of a biological structure or process may be unsuccessful. My intention is to discuss this problem, providing various examples of putative roles of biological structures and processes, which were proposed and generally accepted, but then disproved.