We are interested in molecular recognition: Metal-ligand, pi-pi, donor-acceptor and hydrogen bonding interactions are used to create new supramolecular systems that may have useful recognition, catalytic or photophysical properties. Building blocks include peptides and metalloporphyrins, and products include macrocycles, nanotubes, rotaxanes and catenanes. For more detailed descriptions see our Group Web page (http://www-sanders.ch.cam.ac.uk/)
Inspired by the mammalian immune system, we developed the idea of dynamic combinatorial chemistry. We create a mixture of building blocks and combine them using bond-forming reactions under thermodynamic equilibrating conditions in the presence of a template. The template will gather around itself its optimum host; this host can be selected, amplified, isolated and identified. If the template is a transition state analogue for a reaction, the resulting host might be a good catalyst. The example shown above is a dipeptide building block with an acetal at one end and a hydrazide at the other; under acid conditions these reactive ends combine reversibly to make hydrazone linkers. The resulting mixture, or library, contains many linear and macrocyclic species, but the addition of acetylcholine as a template leads to over 70% yield of the catenane shown: this unpredictable but successful acetylcholine receptor consists of two interlocked trimeric rings. Using the same peptide building block we can also selectively recognize different diastereomers of quinine alkaloids.
The binding properties of a porphyrin depend on the central metal ion, enabling us to create new supramolecular architectures with interesting and unpredictable properties. We create new porphyrin oligomers using Zn, Sn, Al and Rh coordination chemistry, and also create cationic porphyrins that recognize quadruplex DNA.
We have also discovered an entirely new kind of supramolecular nanotube that binds and dissolves C60, and has other potentially interesting properties.
Selected Publications
- A donor-acceptor dynamic combinatorial library in water, Chem. Commun. , (2009), 419
- Two-phase dynamic combinatorial discovery of a spermine transporter, Chem. Commun. , (2009), 3708
- Dynamic combinatorial synthesis of a catenane in water, Proc. Natl Acad. Sci. USA, (2009), 106, 10466
- Dynamic combinatorial chemistry, Chemical Reviews, (2006), 106, 3652
- Hydrogen-bonded helical nanotubes, Angew. Chemie Intl. Edn. , (2007), 46, 194 and 2338
- An unexpected receptor for C70, Angew. Chemie Intl. Edn. , (2008), 47, 2689
- Coordination polymers based on aluminum(III) porphyrins, Inorg. Chem., (2008), 47, 8721