Water-Mediated Folding Behaviors and Chiroptical Inversion of Ferrocene-Conjugated Dipeptides

The hydration effect on the folding
behavior of oligopeptides is
of vital importance both in the structure basis of biomolecules and
in the rational design of peptide-based materials, which however has
rarely been addressed. Here we present the hydration impact on the
spontaneous folding of dipeptides conjugated by the ferrocene spacer.
In organic phase, the ferrocene-glycine-phenylalanine dipeptide formed
a parallel β-sheet structure and Herrick’s conformation,
which underwent conformational transformation encountering aqueous
media, by significantly switching dipeptide arm angles around the
ferrocene axis up to 72°. The conformational transformation behavior
aroused inversion of the chiroptical activity. Solid X-ray structures,
proton nuclear magnetic resonance, chiroptical spectroscopy, and the
density functional theory calculation were employed to unveil the
hydration effect in the secondary structure transition, in which the
rearrangement of hydrogen bonds played the vital role. This work deepens
the understanding of water functioning in the structure modulation
of biomolecules and also provides an alternative protocol in designing
novel chiroptical switches and adaptive peptide-based biomaterials.