We are exploring one of the most exciting frontiers of modern chemistry - the nanoworld. Nanotechnology, the development of systems between 1 and 100 nm in size seems impossible tiny to the average person. However, for chemists, used to manipulating bonds just 0.1 nm long, the nanoworld is a large space, which requires new synthetic strategies.
Nanochemistry - the synthesis and study of nanoscale architectures, is therefore a fundamental part of nanotechnology. Applications of nanotechnology are completely dependent on the new objects which chemists can generate. Our approach uses non-covalent interactions between molecules - ‘supramolecular chemistry’ - in order to allow simple molecular-scale building blocks to spontaneously self-assemble into nanostructures. Self-assembly is a simple and powerful approach to constructing the nanoworld which allows us to generate a wide variety of systems, with applications ranging from nanomaterials to nanomedicine.
Gels are fascinating colloidal materials which surround us in everyday life - from hairgel to jelly babies. Most of the gels we see in everyday life are made of polymers. These large molecules form a 'solid-like' network within a 'liquid-like' solvent - this mix of solid/liquid properties gives rise to the soft solid properties of a gel with which we are all familiar. We are interested in gels which form from small molecules, rather than polymers. The only way this can occur is through self-assembly, in which the molecules interact with one another to form nanofibres held together by non-covalent interactions such as hydrogen bonding.
The key advantage of these 'supramolecular gels' is that they are highly tunable - by designing different functionalities into the small molecules we can ensure that these functions become embedded within the gel-type material once assembly has taken place. The non-covalent interactions allow us to translate information from the molecular scale, up to the nanoscale and hence into macrosopic properties of the gel.
We have carried out fundamental studies of gel assembly, particularly from complex mixtures of different building blocks. The non-covalent interactions which underpin such gels allow order to emerge from complexity. Furthermore, the reversible nature of these maerials means they are highly dynamic and can evolve both over time, and in response to different stimuli. We are currently exploring applications of gel-phase materials in a variety of fields, including sensing, pollution control, aviation technology and tissue engineering.
Biological molecules such as DNA exist on the nanometre length scale. Chemists wanting to intervene in biological processes are therefore increasingly realising that forming interactions with such biomolecules on the nanoscale may be of great therapeutic value. However, although the nanoworld may seem incredibly tiny from the human viewpoint, from the point of view of a molecule, it is a pretty large place (a single bond is just 0.15 nm). As such, we need effective ways of achieving high-affinity binding to nanoscale biological surfaces. One such strategy is multivalency - in which multiple ligands are used to interact with the target. This ‘multi-arm’ strategy is well-known to lead to much higher affinity binding. We are developing our fundamental understanding of multivalent binding in order to bind key biological targets in more controllable ways.
Our interest in binding DNA began in response to my partner having cystic fibrosis, a genetic disease which leads to faulty chloride transport proteins, and ultimately, untimely death. One way of potentially treating genetic diseases is via gene therapy - delivering healthy genetic material into a patient's cells. However, in order to do this, effective vectors are required, which can bind and protect DNA, transport it into cells and allow it to be expressed and 'cure' the cell. We have been working on multivalent systems which can bind DNA with high affinity. In particular, we have developed the approach of self-assembled multivalency, in which small drug-like molecules self-assemble to generate a multivalent nanoscale array. This synthetically simple approach enables high affinity binding, but allows it to be hugely controllable and reversible, potentially of great use in gene delivery.
We are also interested in binding heparin - another negatively charged polymeric biomolecule. This compound plays a vital role as an anti-coagulant in major surgery - a fact we only realised when my partner need to undergo a lung transplant. It would be highly desirable during major surgery for the anaesthetist to monitor heparin-levels in real-time at the bedside, and as such, heparin sensors are of great interest. We have developed a novel multivalent sensor dye, Mallard Blue, which can be made in a simple two-step synthesis and is able to detect heparin selectively in human serum. Furthermore, once surgery is complete, it is necessary to remove heparin from the patient's bloodstream, so that clotting can begin. A significant number of patients have adverse reactions to the current agent, protamine. Designing new heparin rescue agents is therefore also of great interest. We are designing self-assembling multivalent nanoscale systems to target this goal.