Importance of C–H···O Intramolecular Hydrogen Bonding Across a Nonproteinogenic γ-Aminobenzoic Acid Residue: Stabilization of a Flat β-Strand-like Template

Abstract

This paper describes the conformational characteristics of a nonproteinogenic γ-aminobenzoic acid (γ-Abz), investigated experimentally as well as theoretically. The single crystal X-ray diffraction analysis of the model system Boc-γ-Abz-NHMe (1) revealed the existence of an unusual β-strand-like molecular structure. The two weak unconventional C–H···O intramolecular hydrogen-bonds, i.e., main-chain to main-chain: Cβi+1–H···O═Ci+1 and main-chain to side-chain Cδi+1–H···O═Ci interactions, evidently stabilize the flat molecular topology. The favorable antiparallel β-strand mimics are held together by a network of cross-strand N–H···O intermolecular hydrogen bonds. Interestingly, the noncovalent β-sheet-like duplexes facilitate the fabrication of offset face-to-face aromatic–aromatic interactions, whereas the dimers of dimers are aligned edge-to-edge. The two-dimensional 1H NMR ROESY experiment ascertained the extraordinary stability of the rigid β-strand template and molecular self-assembly in a nonpolar environment. The ab initio molecular modeling substantiated the crystal molecular structure as the minimum energy conformer along with weak C–H···O intramolecular hydrogen bonds. The solid-state Fourier transform infrared spectral analysis sustained the participation of both amide-NHs in intermolecular hydrogen bonding. The highly ordered supramolecular architecture, engendered from a single preorganized molecular component, exploited a variety of strong as well as weak stabilizing forces as varied as N–H···O, C–H···O, Ar···Ar, and van der Waals and/or hydrophobic interactions.