Engineered Polyproline Helices for the Rational Design of Supramolecular Constructs

The purpose of this investigation is to determine if novel biocompatible supramolecular constructs with tuneable nanocavities for applications in catalysis, chemical separations, sensing and biomedical applications, can be rationally designed and synthesised utilising polyproline helices as their building blocks. The development of artificial supramolecular systems to mimic complex biological systems has been a longstanding goal of the scientific community and increasingly bioinspired building blocks such as DNA, RNA, aptamers, amino acids, peptides, and proteins have been utilised to develop complex supramolecular systems with promising applications. As such this project aimed to take advantage of the unique properties of the polyproline helix (e.g. rigidity, stability, cis-trans isomerism), and the inherent advantages of peptidic materials (e.g. chirality, periodicity, scalability), to develop peptide-based ligands that can be rationally designed to form desired complex, asymmetric, supramolecular constructs. This requires improving our understanding of the structure and assembly processes of these peptide ligands and how these can compare to the reticular design principles of traditional building-blocks. Therefore, these results will create the potential for the design of further peptide-based supramolecular constructs to produce novel, versatile, biocompatible, functional materials that can be exploited for promising applications.

A series of supramolecular peptide frameworks based on an oligoproline tetramer were synthesised. With these materials we were able to demonstrate the ability to rationally design the peptidic building block to form a variety of porous and non-porous crystalline frameworks depending on the placement of functional groups, while also providing an excellent model for the three-dimensional structure of functionalised polyproline II helices. Thus, highlighting how minimalistic peptide building-blocks can self-assemble to form desired supramolecular assemblies by tuning the supramolecular interactions. Furthermore, the reversible porosity of these peptide frameworks was shown with the ability to incorporate new guest molecules, which was not limited to solvents, with iodine vapour reinflating the peptide framework. Using a chiral guest molecule we were able to demonstrate the enantioselectivity of this absorption process with clear applications for the design and synthesis of functional materials for chemical separations and enantioselective catalysis.

Secondly, a series of functionalised non-natural prolines were synthesised with additional carboxylic acid and pyridine based functional groups. These were incorporated into a variety of peptide sequences to allow for the assembly of metal-peptide constructs via coordination interactions from the functional groups. By varying the functionalisation on each face of the polyproline helix both extended and discrete metal-peptide constructs were synthesised. Nanoparticles were synthesised from metal complexation of a series of polyprolines functionalised on all three helical faces, with the degree of functionalisation, placement of functional groups, and the polyproline helicity (polyproline I vs polyproline II) contributing to the topology of the assembly formed, demonstrating how these ligands can be designed to drive the formation of specific constructs. Furthermore, terminally pyridine functionalised proline tetramers were shown to form discrete palladium complexes in both organic and aqueous solutions. The dimerised peptide complexes expressed selectivity towards a single conformation, highlighting how the chirality of the helix favours a single product over a mixture of metal complex isomers. These complexes show promise for the design of discrete metal-peptide nanocavities as "molecular flasks" for enantioselective catalysis and a clear path to optimise the peptide ligands to form the desired peptide cage structures is discussed.