Dr. Graeme Cooke Department of Chemistry University of Glasgow Glasgow G12 8QQ Scotland Telephone: +44 (0) 141 330 5500 FAX: +44 (0) 141 330 4888 email: graemec@chem.gla.ac.uk

Research Interests

At the present time, research within the group focuses upon the synthesis of supramolecules that have the propensity to undergo electrochemically controllable molecular recognition. We are currently exploiting the virtues of these systems to develop: model systems for flavoenzymes, electrochemically-driven molecular machines and devices and polymers and surfaces with electrochemically tuneable recognition properties.

Keywords: Supramolecular chemistry, materials chemistry, nanochemistry, synthetic chemistry, electrochemistry, molecular machines and devices, macromolecular chemistry, biomimetic chemistry, surface chemistry, physical organic chemistry.

Current research programmes:

1. Biomimetic models to probe flavoenzyme activity.

Flavoenzymes are a ubiquitous class of proteins that catalyse a variety of redox transformations including the oxidation of amines to imines, thiols to disulfides and the hydroxylation of aromatic species. The apoprotein in flavoenzymes serves both to form a binding pocket for the cofactor and to regulate cofactor redox properties. The subtle differences between flavin microenvironment tune the redox properties of the cofactor to meet the function of the given flavoenzyme. X-Ray crystallography has provided a great deal of information about the identities and relative positions of the components of the flavoprotein microenvironment (Figure 1a), but does not yield direct insight into the mechanism or how specific apoprotein/cofactor interactions modulate the redox properties of the latter. One way to address this problem is through the use of appropriate model systems, where interactions between receptor and substrate can be added and tuned systematically to address a given problem. Our current research focuses upon the synthesis of model systems to assess the relative importance that specific supramolecular interactions have in modulating the redox properties of flavins (Figure 1b). More recently we have turned our attention onto the synthesis of flavin-functionalised macromolecular and nanoparticle based systems capable of replicating the structural and catalytic properties of natural flavoenzymes (synzymes).

Figure 1: Showing the active site of a typical flavoenzyme and an example of a synthetic model for roseoflavin.

2. Electrochemically tuneable molecular machines and devices.

The synthesis of interlocked species that can undergo controlled molecular motion is a burgeoning field in endeavours to create rudimentary molecular-scale machines and devices. Our current research focuses upon the application of electrochemistry as tool to facilitate controlled molecular motion within pseudorotaxane and rotaxane architectures.

Figure 2: Structural formula and corresponding X-ray crystal structure of one of our electrochemically controllable flavin-based rotaxanes.

3. Electrochemically tuneable "Plug and play" macromolecules.

In recent research we have developed electrochemically tuneable supramolecular polymers from: side-chain (Figure 3a); telechelic (Figure 3b) and dendrimer (Figure 3c) systems. This redox control offers unrivalled modulation of the macromolecule's properties, creating "plug and play" systems, whereby a diverse range of polymeric structures can be rapidly and reversibly assembled/disassembled.

Figure 3: Electrochemically tuneable (a) side-chain, (b) telechelic and (c) dendrimer systems.

4. Electrochemically tuneable "smart" surfaces.

The application of supramolecular chemistry as a tool for the development of smart surfaces with switchable properties and function is a burgeoning field. In particular, the reversibility, directionality and specificity afforded by non-covalent surface modification has proved to be an attractive method of controlling surface properties and function. Currently, we are exploiting electrochemistry to: tune surface recognition events (e.g. fabrication of write-read-erase surfaces, (Figure 4a)), and control molecular motion within surface-confined interlocked structures (e.g. rotaxanes (Figure 4b)).

Figure 4: Examples of our electrochemically tuneable smart surfaces: (a) write-read-erase surfaces and (b) an example of an electropolymerised [2]rotaxane.

Vacancies:

For information regarding PhD studentships and post-doctoral fellowships within the group please contact G. Cooke (graemec@chem.gla.ac.uk).

Selected recent publications:

1. GALLOW TH, ILHAN F, COOKE G & ROTELLO VM. "Encapsulation of an Electroactive Guest Within a Dynamically Folded Polymer." Journal of the American Chemical Society 122, 2000, 3595-3598.
2. BODEN N, BUSHBY RJ, COOKE G, LOZMAN OR & LU Z. "CPI - A recipe for improving applicable properties of discotic liquid crystals." Journal of the American Chemical Society 123, 2001, 7915-7916.
3. BOURGEL C, BOYD ASF, COOKE G, DE CREMIERS HA, DUCLAIROIR FM & ROTELLO VM. "The first redox controlled hydrogen bonded three-pole switch." Chemical Communications 2001, 1954-1955.
4. DE CREMIERS HA CLAVIER G, ILHAN F, COOKE G & ROTELLO VM, "Tuneable Electrochemical Interactions Between Polystyrenes with Anthracenyl and Tetrathiafulvalenyl Sidechains." Chemical Communications 2001, 2232-2233.
5. BEEBY A, BRYCE MR, CHRISTENSEN CA, COOKE G, DUCLAIROIR FMA & ROTELLO VM. "Electrochemically Controlled Interactions between TTF-based Dendrimers and an Electron Rich Oligomer." Chemical Communications 2002, 2950-2951.
6. BOYD ASF, COOKE G, DUCLAIROIR FMA & ROTELLO VM, "An Investigation of The Role of The Disparate Redox States of The Tetrathiafulvalene Unit in Modulating Hydrogen Bonding Interactions in Solution." Tetrahedron Letters 44, 2003, 303-306.
7. COOKE G, DE CREMIERS HA, DUCLAIROIR FMA, LEONARDI J, ROSAIR G & ROTELLO VM, "Ferrocene Incorporating Host-Guest Dyads With Electrochemically Controlled Three-Pole Hydrogen Bonding Properties." Tetrahedron 59, 2003, 3341-3347.
8. COOKE G, SINDELAR V & ROTELLO V. "The Electrochemically Controlled Hydrogen Bond Formation Between a Phenyl-Urea Terminated Dendrimer and Phenanthrenequinone." Chemical Communications 2003, 752-753.
9. BRYCE MR, COOKE G, DUCLAIROIR FMA, JOHN P, PEREPICHKA DE, POLWART N, ROTELLO VM, STODDART JF & TSENG HR., "Surface Confined Pseudorotaxanes with Electrochemically Controllable Complexation Properties." Journal of Materials Chemistry 13, 2003, 2111-2117.
10. GRAY M, CUELLO AO, COOKE G & ROTELLO VM. Hydrogen Bonding in Redox-Modulated Molecular Recognition. "An Experimental and Theoretical Investigation." Journal of the American Chemical Society 125, 2003. 7882-7888.
11. COOKE G, DUCLAIROIR F, JOHN P, POLWART N & ROTELLO V. "Model Systems for Flavoenzyme Activity: Flavin-Functionalised SAMs as Models for Probing Redox Modulation Through Hydrogen Bonding." Chemical Communications 2003, 2468-2469.
12. LEGRAND YM, GRAY M, COOKE G & ROTELLO VM. "Model Systems for Flavoenzyme Activity: Relationships between cofactor structure, binding and redox properties." Journal American Chemical Society 125, 2003, 15789-15795.
13. COOKE G, DUCLAIROIR FMA, KRAFT A, ROSAIR G & ROTELLO VM. "Pronounced Stabilisation of the Ferrocenium State of Ferrocenecarboxylic acid by Salt Bridge Formation with a Benzamidine." Tetrahedron Letters 45, 2004, 557-560.
14. GRAY M, GOODMAN AJ, CARROLL JB, BARDON K, MARKEY M, COOKE G & ROTELLO VM. "Model Systems for Flavoenzyme Activity: Interplay of Hydrogen Bonding and Aromatic Stacking In Cofactor Redox Modulation." Organic Letters 6, 2004, 385-388.
15. CARROLL JB, GRAY M, COOKE G, & ROTELLO VM. "Proton Transfer versus Redox Modulation in Thiourea-Phenanthrenequinone Molecular and Polymeric Complexes." Chemical Communications 2004, 442-443.
16. COOKE G, LEGRAND YM & ROTELLO VM. "Model Systems for Flavoenzyme Activity: An Electrochemically Tuneable Model of Roseoflavin." Chemical Communications 2004, 1088-1089.
17. COOKE G, GARETY JF, MABRUK S, ROTELLO VM, SURPATEANU G & WOISEL P. "The Electrochemically Tuneable Recognition Properties of An Electropolymerised Flavin Derivative." Chemical Communications 2004, 2722-2723.
18. BOYD ASF, CARROLL J, COOKE G, GARETY JF, MABRUK S, ROSAIR G & ROTELLO VM, "Model Systems for Flavoenzyme Activity: An Electrochemically Tuneable Intramolecularly Hydrogen Bonded Flavin-Diamidopyridine Complex." Chemical Communications 2005, 2468-2470.
19. CARROLL J, JORDAN, BJ, XU H, ERDOGAN B, LEE L, CHENG L, TIERNAN C, COOKE G, & ROTELLO VM, "Model Systems for Flavoenzyme Activity: Site Isolated Redox Behavior in Clicked Flavin Functionalised Random Polystyrene Copolymers. " Organic Letters 7, 2005, 2551-2554.
20. CARROLL JB, COOKE G, GARETY JF, JORDAN BJ, MABRUK S, ROTELLO VM. "The Electrochemically Tuneable Interactions Between Flavin-Functionalised C60 Derivatives and 2,6-Diethylamidopyridine." Chemical Communications 2005, 3838-3840.
21. COOKE G, GARETY JF, MABRUK S, RABANI G, ROTELLO VM, SURPATEANU, WOISEL P. "An Electropolymerisable [2]Rotaxane." Tetrahedron Letters 47, 2006, 783-786.