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.
