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Beilstein Symposium on Systems Chemistry, Day 1

I’ve been invited to deliver the summary talk for the 2008 Beilstein Symposium on Systems Chemistry in Bolzano, Italy. Being there for the fourth time in eight years (this symposium is biannual) I really always enjoy the meeting in this beautiful setting from the very first minute. The fact that the view and the food is fantastic and that Schloss Korb is a winery of course plays no role. My interest is purely scientific 🙂

Following are my notes on the various talks, hopefully helping me to put together the summary in the end. All of the talks were full of subtle, interestingly illustrated scientific details which were absolutely impossible to capture here 🙂

Tuesday morning: Life, Living Systems and their inherent properties

Martin Hicks, organizing the Beilstein workshop in Bozen in the twentieth year now, in his introduction highlights the routes between synthetic chemistry and biological systems. He also points to the different views of Chemists and Biologists on Biological Systems. And, as you will probably appreciate, 20 rabbits do not make a horse.

• Günter von Kiedrowski, in “Systems Chemistry and the Origin of Life”, puts the understanding of the origin of life in the centre of interest of Systems Chemistry. Showing a picture of earth from space he points out the number of events necessary to form life on earth, including formation of the hydrosphere, cometary impacts, formation of the RNA world, as well as an DNA-Protein world: Prebiotic chemistry. He calls it “Origin of Life” research and acknowledges Jean-Marie Lehn, Albert Eschenmoser and Manfred Eigen as pioneers. Günter mentions Craig Venter’s minimal Cell and works on Minimal Self-Replicating System: Keypoint is a product inhibition preventing exponential growth of the system. He further shows basic structural and dynamic prerequisites for self-replicating system. My impression was that the kinetic rules for a minimal replicator are well understood. In the last slide, he sites the NASA exobiology program: “Life: A self-sustaining chemical system capable of undergoing Darwinian evolution”

• The second speaker, well-known Hans V. Westerhoff from Amsterdam in “Chemistry in Three Dimensions: How Systems’s Biology may Regulate its System’s Chemsitry”, looks at chemistry from a systems biology view point. He points out that the European Science Foundation has declared Systems Biology a Grand Challenge with implications for the understanding and fight against disease. His talk focused on some fundamental properties of chemical and biological systems which I mostly missed. Mentions plan to make the virtual human in the next 30 years.

• Antoine Danchin started of by talking about using Synthetic Biology (SB) for constructing a synthetic cell . The first aim of SB is to reconstruct life. He introduces the idea that the cell might be Turing machine. Life as a combination of a program running on a cell processor. He points out that while the machines reproduces, the program replicates. Replication accumulates errors. An interesting fact: One fifth of bacterial genomes comes from “outside”, a hint of the separation of program and hardware, kind of an organic open source software exchange. Antoine also introduces the notions of the Paleome, part of the genome responsible for replication and maintenance, and the Cenome , managing Life in context, sensing, etc.

• Athel Cornish-Bowden, in “Catalysis at the Origin of Life” promotes ideas by Robert Rosen in exemplifying an Algebraic Representation of Metabolism, based on Rosen’s Metabolism-Repair/Replacement system theory.

Tuesday afternoon: Catalysis and Chemical Tools for Exploring Biology (Chemical Biology)

• The afternoon session of the first day was opened by Benjamin List, who talked about “New Concepts for Catalysis”. Benjamin highlights progress in the understanding of catalytic properties of small organic molecules without involvement of metals as part of the catalytic principle.
• Steve Ley of Cambridge presented on”New Tools for Molecule Maker: Emerging Technologies”. His main interest is in making molecules, and making these with some goal in mind, such as curing a disease. He starts off with asking how good we really are as organic chemists. A slide with examples of synthesized, quite complicated natural products his lab had synthesized in the past. Pretty impressive, but he points out the limitations: Less severe are lack of reproducibility, scale-up issues, problems with low temperature, material economy. Really bad: Current cost of organic chemistry, time consumption, wastage of man power and questions of sustainability. The solution are flow reactors and lab-on-a-chip devices. Steve shows the synthesis of Epothilones on beads, requiring no washing, no isolation, no chromatography. Flow mode chemistry, combined with the beads concept makes synthesis even more efficient. Like the following speaker, Steve shows a continuous flow reactor chip (lab-on-a-chip), coupled to collectors, HPLC and a recycling loop, pointing out that the whole dynamics of a reaction change (as in “enormous speed-up”) when going from flasks to flow reactors. The close-loop-operation of these devices allow for rapid, even on-the-fly changes and improvements of reaction conditions. An interesting point was that chemists are awfully bad in achieving proper mixing of reaction mixtures and that the ability to pump reaction mixtures back and forth in flow reactors significantly changes the rules of the games, dramatically increasing the reaction rates. These things can then be made in amounts to up to 15 kg in the Ley lab!
• Peter Seeberger of ETH Zürich , who has just accepted a call to become a director of a Max-Planck-Institute near Berlin, also talked about “Microreactors as Tools for Organic Synthesis”. He points out, underpinned by pictures from MIT labs through the ages, that the chemistry lab has not changed much in the last hundred years. Besides advantages also pointed out by Steve Ley, Peter emphasizes the positive safety behaviour of flow-through reactors. The flow reactors that he describes are silicon-based with the advantage that the production process for these reactor is very well understood (think “chip industry”). Like Steve, Peter points out that flow reactors allows a coworker in his lab to run a couple of hundred reactions under different conditions in a few afternoons. Besides making things faster and more efficient, you even make things that don’t work otherwise. He exemplifies this with the synthesis of a particular tetrapeptide, where I missed the point why this was not possible without flow devices.
• Eric Meggers, University of Marburg and Wistar Institute, Philadelphia, concluded the afternoon session, with a talk on “Chemical Biology with Organometallics”. Why is Nature synthesizing complicated secondary metabolites, is his starting question, while drugs, for example, often look so much simpler. He exemplifies by showing how nicely Geldamycin fits into its target pocket – an example already answering his question. The target pocket is flat and wide and Geldamycin adopts a bulky globular shape with all functional groups nicely presented on its surface. No smaller or less complicated molecule could have this function. He then introduced a recipe for morphing indolocarbazole alkaloids into simple and easily accessible metal complexes, leading to potent inhibitors of protein kinases.

I’ll send this off now, because the reception this evening will be in the local wine cellar. No more sensible content to be expected.

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Categorised as: Conferences and Meetings, Hot Science