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Peptide-like foldamers controlled by normal amide backbone hydrogen bonding have been extensively studied, and their folding patterns largely rely on configurational and conformational constraints induced by the steric properties of backbone substituents at appropriate positions. In contrast, opportunities to influence peptide secondary structure by functional groups forming individual hydrogen bond networks have not received much attention. Here, peptide-like foldamers consisting of alternating α,β,γ-triamino acids 3-amino-4-(aminomethyl)-2-methylpyrrolidine-3-carboxylate (AAMP) and natural amino acids glycine and alanine are reported, which were obtained by solution phase peptide synthesis. They form ordered secondary structures, which are dominated by a three-dimensional bridged triazaspiranoid-like hydrogen bond network involving the non-backbone amino groups, the backbone amide hydrogen bonds, and the relative configuration of the α,β,γ-triamino and α-amino acid building blocks. This additional stabilization leads to folding in both nonpolar organic as well as in aqueous environments. The three-dimensional arrangement of the individual foldamers is supported by X-ray crystallography, NMR spectroscopy, chiroptical methods, and molecular dynamics simulations. Peptide-like foldamers are known to be controlled by amide backbone hydrogen bonding, however, the influence of functional groups forming individual hydrogen-bond networks remains underexplored. Here, the authors report peptide-like α-γ heterofoldamers consisting of alternating α,β,γ-triamino acids, forming ordered secondary structures and folding in both organic and aqueous environments. [ABSTRACT FROM AUTHOR]

The crystal structures of the title compounds consist of 1,4-dimethyl-1,4-diazabicyclo[2.2.2]octane-1,4-diium cation [CHN] and [HPO] or [HSO] anions. Both crystal structures are monoclinic, the structure of the dihydrogen phosphate ( I) is non-centrosymmetric ( P2) with a = 6.4090(2) Å, b = 13.6920(5) Å, c = 7.6140(3) Å, β = 94.620(2)°, V = 665.97(4) Å, Z = 2; whereas the unit cell of the hydrogen sulphate ( II) is centrosymmetric ( P2/ c) with a = 13.8460(2) Å, b = 12.6610(2) Å, c = 8.0360(2) Å, β = 99.5800(12)°, V = 1389.10(5) Å, Z = 4. Both the structures are formed by the different bonding patterns of the anions interlinked by strong and moderate O-H···O hydrogen bonds. While the structure of ( I) consists of a two-dimensional network of the hydrogen bonded dihydrogen phosphates, the infinite chains of the hydrogen bonded hydrogen sulphates are the basic building unit of the structure ( II). In addition to the dominant electrostatic interaction the divalent cations stabilize themselves in the structures by forming several C-H···O hydrogen bonds to the oxygen atoms of the anions. The IR spectra of both the compounds are strongly affected by the hydrogen bonds whose influence on OH stretching vibrations is analysed by means of the DFT calculations in the solid state. Graphical Abstract: The crystal structures of the 1,4-dimethyl-1,4-diazabicyclo[2.2.2]octane-1,4-diium dihydrogen phosphate and hydrogen sulphate comprise strong and moderate O-H···O hydrogen bonds significantly influencing the high energy region of IR spectra.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]