Functional Hydrogen-Bonded Self-Sorting Networks

In biology, multiple processes occur simultaneously to perform the functions necessary for life e.g. manufacture and destruction of cells. To do this, multicomponent architectures comprising several different components or building blocks (e.g. proteins) must assemble with exquisite control at the right time and in the right place. Such multiple component architectures may also need to disassemble and reassemble into new architectures with different function at another time. These systems can therefore be considered as networks that form different functional architectures in an environmentally responsive manner. What makes the assembly and function of such architectures possible is self-sorting - the ability of one component to recognise its correct partner component(s) in the presence of many others. Synthetic chemistry is not yet capable of mimicking functional self-sorting networks. This research will address this challenge and develop the first non-natural (synthetic) functional self-sorting networks. We will use patterns of hydrogen-bonding motifs (HBMs), which mimic the DNA base pairs used to store genetic information, to construct self-sorting networks. We will then use these HBMS to control a series of catalytic and iterative synthetic chemistry processes. In the long term such methods could be used to prepare industrially important fine chemicals and pharmaceuticals in a similar manner to assembly lines used in modern manufacturing, offering advantages in complexity and efficiency.

Systems Chemistry is an emerging topic focussed on understanding networks of interacting molecules, and using this understanding to develop new functions. In biology, self-sorting facilitates biosynthesis of compositionally and structurally diverse small-molecules, together with tight control over when and where these are produced, through co-ordinated assembly of multi-subunit supramolecular complexes that can be reconfigured under different environmental circumstances. This capability is beyond synthetic chemistry at this time. Therefore this research will develop the underlying conceptual framework to exploit self-sorting hydrogen-bonding networks for (i) regulated catalysis and (ii) processive synthesis. In the long term, development of the modular and protecting group free nature of processive synthetic methodology could, applied to synthetic transformations not found in biology, transform approaches to synthesis in the pharmaceutical and fine chemicals industry, with significant opportunities for combinatorial methods and efficiency. The research theme aligns with both the Directed Assembly and Dial-a-Molecule Grand Challenge networks which both support the development of the UKs next generation of disruptive technologies. The immediate impact of this research will be to:

(i) foster new collaboration between the investigators;

(ii) engage scientists across a range of career stages in this field and develop their capabilities;

(iii) bridge to efforts in the area of synthetic biology which has been identified as a key technology to promote future prosperity and address societal challenges; specifically the design and engineering of biologically based parts for new applications, and;

(iv) promote this approach and build the network of industrial and academic partners to exploit translational opportunities identified during the research and ensure appropriate follow-on activities occur.