Foldamer Metallogels: Metal Driven Supramolecular Assembly of Peptide Foldamers

Abstract

Metals play a crucial role in the structure and functions of various proteins. The metal containing active sites of metalloproteins are responsible for important biological processes such as photosynthesis, oxygen transport and storage, respiration and nitrogen fixation. In addition, metals also play an important role in the amyloidogenesis. Inspired by these fascinating properties, chemists have been trying to mimic naturally occurring metalloproteins by synthesizing artificial peptides attached with natural or nonnatural metal-binding ligands. Over the past few decades, this strategy has emerged as an important field in the area of supramolecular chemistry and have contributed several supramolecular architectures with potential applications. The design of such novel architectures from peptides requires deep understanding on their structural properties, assembly behaviors and dynamic nature. Motivated by the diverse functions of metallopeptides and proteins, we sought to investigate whether the metals can be used to drive the ordered supramolecular assemblies in hybrid peptide foldamers. Herein, we are presenting the studies on the metal driven supramolecular assembly of peptide foldamers exhibiting diverse structural and assembly properties. The designed tripeptide β sheets with 3-pyridyl ligands at their both termini displayed remarkable supramolecular metallogel upon Ag(I) coordination polymerization. Replacing 3-pyridyl ligands with 4- pyridyl ligands in the same sequence resulted in the formation of Cu(II) metallogel. In contrast, on replacing leucine residue with γ-leucine in these -peptide sequence resulted in a complete structural transformation from β sheets to 12-helices, as evident from X-ray diffraction analysis. Surprisingly, both these helical peptides self-assembled to form stable metallo-foldamer-gels. In sharp contrast to this observation, the coordinationdriven self-assembly of a more stable helical foldamer, designed by incorporating the helix inducer amino acid Aib in its sequence, did not lead to metallogels. However, it produced X-ray quality single crystals and the structural analysis of this complex revealed that the helical structure of the peptide is retained in the complex. From these observations, we hypothesize that the formation of metallogels from helical foldamer ligands may arise from their coordination driven unfolding.