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Catalysts are becoming more and more important every day. A catalyst changes the pathway of a reaction such that formation of one product is favoured over other products. Consequently, the reaction becomes more selective and less waste is produced, also making purification easier. Another advantage is that catalysts accelerate reaction rates reducing energy consumption.Enzymes are nature's catalysts. They are in general more efficient both in speed and selectivity then man-made catalysts, but they cannot perform all the reaction we would like, such as hydroformylation. Man-made catalysts employing a transition metal are very efficient in these reactions.We aim to utilise the molecular recognition which oligonucleotides exhibit and combine that with the activity of transition metals to create artificial metallo DNAzymes. These metallo DNAzymes can then be used in industrial relevant catalytic reactions for which no enzyme exists such as hydroformylation, allylic substitution and hydrogenation to name a few. Two approaches can be envisioned: the supramolecular approach where the metal is non covalently bound to oligonucleotides[1] and the covalent approach where the transition metal is covalently attach to the DNA strand, often through a linker.In the first case a racemic or nonchiral ligand capable of both coordinating to a metal and binding to DNA is introduced to a DNA strand via self assembly. This approach has the clear advantage that catalyst can be optimised using commercially available DNA instead of synthesising each strand individually. Unfortunately it is unclear where the catalytic centre is located as the ligand has the potential to bind to numerous places in the DNA double helix. The covalent approach overcomes this problem by coordinating the transition metal directly to a linker bound to DNA. The disadvantage of this approach is that it is much more labour intensive, requiring complicated and troublesome synthetic methods.Both Jschke[2] and our group[3] have used this approach after which these DNA oligonucleotides were coordinated to iridium and palladium respectively and used in allylic amination. Although the enantioselectivities were moderate it indicates that this approach does work. By changing the base sequence and increasing the chain length the enantioselectivity might be increased.We plan to combine both approaches. Dervan et al.[4] have developed polyamide chains that bind to specific DNA sequences which we will modify by attaching a ligand capable of coordinating to a transition metal to it. After metal coordination the polyamide can be coupled selectively to a DNA double helix containing the correct sequence. These novel catalysts will then be tested in transition metal mediated conversions.Using the same approach different transition metal complexes will be immobilized on two-dimensional crystalline DNA arrays aiming at cascade catalytic conversions.This pilot study by the PhD student will be supervised by the PI and Prof. Dervan at Caltech and is aiming at long term collaboration between the two groups via follow-up joint grant proposals.1. Dijk, E. W.; Feringa, B. L.; Roelfes, G., Top Organomet. Chem. 2009, 25, 1.2. Fournier, P.; Fiammengo, R.; Jschke, A., Angew. Chem. Int. Ed. 2009, 48, 1.3. Ropartz, L.; Meeuwenoord, N. J.; Marel, G. A. v. d.; Leeuwen, P. W. N. M. v.; Slawin, A. M. Z.; Kamer, P. C. J., Chem. Commun. 2007, 1556.4. Hsu, C. F.; Phillips, J. W.; Trauger, J. W.; Farkas, M. E.; Belitsky, J. M.; Heckel, A.; Olenyuk, B. Z.; Puckett, J. W.; Wang, C. C. C.; Dervan, P. B., Tetrahedron 2007, 63, 6146.
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