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Dr Niklaas Buurma  -  MRSC, FHEA


DNA is an important target for potential drugs and genosensors. Molecules allowing control over selectivity and affinity for DNA are therefore of particular interest as genosensors (and/or therapeutic agents). We develop new DNA-binding motifs consisting of fully conjugated systems which display changes in optoelectronic properties upon interaction with DNA. As an example of this approach, we have recently elucidated the binding mode and quantified the affinity of several cationically substituted oligothiophenes with DNA. Further work on additional conjugated oligoheteroaromatics is ongoing with the final aim to develop sequence-selective conjugated polymers for use as genosensors.

Apart from being an interesting target for biomedical applications, DNA in itself forms a versatile building block for a range of 3D structures. Combining these 3D structures with DNA-binding molecules having interesting electronic properties opens up the world of nanobioelectronics.

One of the techniques used for the study of interactions with DNA and other (bio)macromolecules is isothermal titration calorimetry (ITC). We have developed, and continue to develop, data analysis software for complex (coupled) equilibria. Our software allows the modular combination of interaction processes coupled with powerful post-fit parameter-validity analysis procedures, ensuring maximum flexibility in data analysis while keeping parameters statistically significant.

Our interest in organic reactivity focuses on aqueous solutions. A key interest is the use of micellar solutions. Micelles can be employed as colloidal catalysts (or catalyst supports) in aqueous solutions for a variety of reactions. In order to optimise the catalytic properties of micelles, we need to understand their properties as a reaction medium. We have developed a model that describes the local reaction medium provided by micelles. Based on our analysis, model solutions accurately mimicking the reaction medium as offered by micelles can be prepared. This in turn allows tuning of activity and selectivity of surfactant based catalysts.

We apply our understanding of the local reaction medium offered by micelles in the development of micelle-assisted transition metal-catalysed reactions. A representative system of current interest involves the oxidative coupling of boronic acids. Very recently, we have also ventured into approaches using nanoparticles.

In collaboration with AstraZeneca, we study the kinetics and mechanism of racemisation reactions in aqueous solutions. As part of this project, we develop the use of VCD for kinetic and mechanistic studies.

Finally, our studies of reactions and interactions require development of mathematical models for the analysis of experimental data. For example, in addition to our software for the analysis of complex ITC data, we have developed models for the global analysis of pH- and temperature-dependent enzyme kinetics and for the analysis of kinetic data for catalysis by gold nanoparticles encapsulated within a thermosensitive shell.

 

Fig 1Diagram