Herical

During viral cell entry, the spike protein of SARS-CoV-2 binds to the α1-helix motif of human angiotensin-converting enzyme 2 (ACE2). Thus, alpha-helical peptides mimicking this motif may serve as inhibitors of viral cell entry. For this purpose, we employed the rigidified diproline-derived module ProM-5 to induce α-helicity in short peptide sequences inspired by the ACE2 α1-helix. Starting with Ac-QAKTFLDKFNHEAEDLFYQ-NH2 as a relevant section of α1, a series of peptides, N-capped with either Ac-βHAsp-[ProM-5] or Ac-βHAsp-PP, were prepared and their α-helicities were investigated. While ProM-5 clearly showed a pronounced effect, an even increased degree of helicity (up to 63 %) was observed in sequences in which non-binding amino acids were replaced by alanine. The binding affinities of the peptides towards the spike protein, as determined by means of microscale thermophoresis (MST), revealed only a subtle influence of the α-helical content and, noteworthy, led to the identification of an Ac-βHAsp-PP-capped peptide displaying a very strong binding affinity (KD =62 nM).

Polymer chains, if long enough, are known to undergo bond scission when mechanically stressed. While the mechanochemical response of random coils is well understood, biopolymers and some key synthetic chains adopt well-defined secondary structures such as helices. To understand covalent mechanochemistry in such structures, poly(γ-benzyl glutamates) are prepared while regulating the feed-monomer chirality, producing chains with similar molecular weights and backbone chemistry but different helicities. Such chains are stressed in solution and their mechanochemistry rates compared by following molecular weight change and using a rhodamine mechanochromophore. Results reveal that while helicity itself is not affected by the covalent bond scissions, chains with higher helicity undergo faster mechanochemistry. Considering that the polymers tested differ only in conformation, these results indicate that helix-induced chain rigidity improves the efficiency of mechanical energy transduction.

The [N···I···N]+ type halogen bond has been utilized to synthesize supramolecular architectures, while the applications in constructing helical motifs and modulating supramolecular chirality have been unexplored so far. In this work, the [N···I···N]+ halogen bond was introduced to drive the formation of supramolecular helical polymers via a Ag(I) coordination intermediate, showing tunable supramolecular chirality. Pyridine segments were conjugated to the asymmetric ferrocene skeleton, which show "open" and "closed" geometry depending on the sp2 N positions. Coordination with Ag(I) generated one-dimensional (1D) double helices and 2D helicates featured the [Ag(O)···I···Ag(O)]+ bond, which further stacked into 3D porous frameworks with chiral channels and adjustable pore sizes. Ionic exchange afforded 1D supramolecular helical polymers in solution phases driven by the [N···I···N]+ type halogen bonds, which was evidenced by the experimental results and density functional theory calculation. Fc2 exclusively demonstrated tunable supramolecular chirality in the formation of coordinated and halogen bonded polymers. In addition, solvent change would further inverse the helicity of halogen bonded supramolecular helical polymers depending on the rotation of the ferrocenyl core whose "closed" and "open" states were accompanied by the breakage of intramolecular hydrogen bonds. This work introduces a [N···I···N]+ type ionic halogen bond to prepare supramolecular helical polymers, providing multiple protocols in regulating helicity by ion exchange and solvent environments.