A Reversibly Porous Supramolecular Peptide Framework**

Abstract

The ability to use bio-inspired building-blocks in the assembly of novel supramolecular frameworks is at the forefront of this exciting research field. Herein, we present the first polyproline helix to self-assemble into a reversibly porous, crystalline, supramolecular peptide framework (SPF). This framework is assembled from a short oligoproline, adopting the polyproline II conformation, driven by hydrogen-bonding and dispersion interactions. Thermal activation, guest-induced dynamic porosity and enantioselective guest inclusion have been demonstrated for this novel system. The principles of the self-assembly associated with this SPF will be used as a blueprint allowing for the further development of helical peptide linkers in the rational design of SPFs and metalpeptide frameworks.

Supramolecular Self-assembly of Engineered Polyproline Helices

“…Interestingly this framework adopted the endo conformation similarly to P4 alone, having significantly less impact on the channel volume, and thus contained EtOH within the pores rather than H2O (Figure 5-6c). As mentioned previously the P4 peptide framework could be activated by heating (45 o C) under reduced pressure, 24 with characterisation through both PDXRD and SCXRD showing encapsulated EtOH had been removed, forming a collapsed non-porous structure. As the mixed framework exhibited a very similar structure to the P4 framework, with EtOH encapsulated in accessible channels(Figure 5-6), while the P2HP peptide framework contained water trapped in isolated pores (Figure 5b-6b), and significantly showed no change after attempted activation (SI 3.2.4, Figure S42), we anticipated the mixed framework would exhibit different behaviour to the peptides alone.…”

“…, This change in properties of the framework was exemplified through the repetition of thermal activation studies carried out on the P4 framework previously, whereby encapsulated solvent could be removed resulting in the collapse of the channels forming a non-porous structure. 24 In this case heating the P2HP framework under reduced pressure at 45 o C did not show the formation of a second crystalline phase (Figure S42, SI 3.2.4), showing how the solvent filled voids are now trapped in place by the additional hydroxyl moieties. This ability to functionalise the pores of the framework with no disruption of the peptide helix, thereby allowing tuning of the selectivity of the pores has clear applications towards specific host-guest interactions.…”

“…Analysing the crystal structure of P4 we were able to observe that the terminal prolines, Pro1 (Nterminus) and Pro4 (C-terminus), clearly have close contacts with the neighbouring peptide along the b-axis (Figure 2), 24 suggesting hydroxyl groups at these positions are likely to extend new hydrogen- bonding interactions along the axis without significantly impacting the packing topology. As such a series of peptides were synthesised by replacing the terminal prolines with hydroxyprolines, these were peptides; HP3, P3H, HP2H, Cis-HP2H, and AcHP2H (Figure 1).…”

“…We have recently demonstrated that super short polyproline helices (tetrameric peptides) can assemble into a reversibly porous supramolecular peptide framework (SPF) capable of engaging in stereoselective host encapsulation. 24 Herein, we demonstrate the ability to utilise functionalised short polyproline helices as predictable ligands with an exceptional level of control, for the rational design of series of H-bonding driven supramolecular peptide frameworks. The design principles successfully applied to these peptides, can be used to drive the design of more complex peptide-based materials.…”

“…28 This SPF showed remarkable reversible porosity, the ability to reversibly host chemical guests in its channels and exhibited enantioselectivity for this adsorption process. 24 The formation of this porous framework was driven by hydrogen-bond donor and acceptor (HD-HA) interactions between the hydrogens of the primary amide at the Cterminus and the carbonyl groups on the peptide backbone. These results gave us an insight into the potential of short polyproline helices as supramolecular building blocks.…”