Crystal structure of Boc-(S)-ABOC-(S)-Ala-(S)-ABOC-(S)-Phe-OBn chloroform monosolvate

In the title compound, the α,β-hybrid peptide contains two non-proteinogenic amino acid residues [(S)-ABOC], two amino acid residues [(S)-Ala and (S)-Phe], and protecting groups of Boc and OBn. The tetramer folds into a right-handed mixed 11/9 helix stabilized by intramolecular i,i + 3 and i,i-1 C=O⋯H—N hydrogen bonds. The oligomers are linked into chains by N—H⋯O=C hydrogen bonds with the chloroform solvent molecules intercalated between the folded chains via C—H⋯O=C interactions.

, and protecting groups of tert-butoxycarbonyl (Boc) and benzyl ester (OBn). The tetramer folds into a right-handed mixed 11/9 helix stabilized by intramolecular i,i + 3 and i,i À 1 C OÁ Á ÁH-N hydrogen bonds. In the crystal, the oligomers are linked by N-HÁ Á ÁO C hydrogen bonds into chains along the a-axis direction. The chloroform solvent molecules are intercalated between the folded chains via C-HÁ Á ÁO C interactions.

Chemical context
The title compound is an ,-hybrid tetrapeptide with alternating proteogenic -amino acid and ABOC residues. (S)-1aminobicyclo[2.2.2]octane-2-carboxylic acid [(S)-ABOC] is a 2,3,3 -trisubstituted bicyclic amino acid which exhibits a high propensity to induce both a reverse turn into short peptides and helices in oligoureas and in ,-hybrid peptides (Songis et al., 2007;André et al., 2012André et al., , 2013Legrand et al., 2012Legrand et al., , 2014. In our last study we showed that short oligomers adopted an 11/9 helix, whereas an 18/16 helix was favored for longer oligomers in solution. NMR studies suggested a rapid interconversion between the 11/9 helix and the 18/16 helix for oligomers of intermediate length. In the solid state, only the 11/9 helix has been observed whatever the length of the oligomers capped by an iPrCO and an OBn group (Legrand et al., 2014).

Structural commentary
For the title compound ( Fig. 1), the triclinic unit cell consists of one molecule of ,-hybrid tetramer and one molecule of chloroform. The oligomer exhibits a right-handed mixed 11/9 11/9 helix as the title compound while the hydrogen-bond network is incomplete in the other molecule. The last C9 hydrogen bond between the carbonyl of the Phe residue and the -residue amide proton was disrupted by the incorporation of a water molecule (Legrand et al., 2014). This intercalation of water molecules has already been observed in oligoureas (Legrand et al., 2012) and highlighted in an enzyme involved in the mitochondrial respiratory chain i.e. the mitochondrial bc1 complex. Its bovine crystal structure (Huang et al., 2005) revealed that an intercalated water molecule in an -helix took part in the stabilization of the high potential cytochrome b heme. Usually, -helices interact laterally with their side chains. Water molecules adsorption on an -helice groove is an alternative tool available to the helical system to interact with partners.
For further related articles on hybrid peptides, see: Hayen et al. The molecular structure of the title compound showing the atomnumbering scheme. All non-H atoms are represented by 25% probability displacement ellipsoids. H atoms are omitted for clarity. Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
Partial packing view of the title compound in the ac plane.

Synthesis and crystallization
The synthesis of the title compound has recently been reported by Legrand et al. (2014). Single crystals were obtained by slow evaporation of a chloroform solution.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms were located in a difference Fourier map. The C/N-bonded H atoms were placed at calculated positions and refined using a riding model, with C-H = 0.95-1.00 Å and N-H = 0.88 Å . The U iso (H) parameters were fixed at 1.2U eq (C, N) for methine, methylene, aromatic groups and NH groups, and at 1.5U eq (C) for methyl groups.