Conformation control through concurrent N-HMIDLINE HORIZONTAL ELLIPSISS and N-HMIDLINE HORIZONTAL ELLIPSISO-C hydrogen bonding and hyperconjugation effects

In addition to the classical N-HMIDLINE HORIZONTAL ELLIPSISO-C non-covalent interaction, less conventional types of hydrogen bonding, such as N-HMIDLINE HORIZONTAL ELLIPSISS, may play a key role in determining the molecular structure. In this work, using theoretical calculations in combination with spectroscopic analysis in both gas phase and solution phase, we demonstrate that both these H-bonding modes exist simultaneously in low-energy conformers of capped derivatives of Attc, a thietane alpha-amino acid. 6-Membered ring inter-residue N-HMIDLINE HORIZONTAL ELLIPSISS interactions (C6(gamma)), assisted by hyperconjugation between the thietane ring and the backbone, combine with 5-membered ring intra-residue backbone N-HMIDLINE HORIZONTAL ELLIPSISO-C interactions (C5) to provide a C5-C6(gamma)feature that stabilizes a planar geometry in the monomer unit. Two contiguous C5-C6(gamma)features in the planar dimer implicate an unprecedented three-centre H-bond of the type C-OMIDLINE HORIZONTAL ELLIPSISH(N)MIDLINE HORIZONTAL ELLIPSISSR2, while the trimer adopts two C5-C6(gamma)features separated by a Ramachandran alpha-type backbone configuration. These low-energy conformers are fully characterized in the gas phase and support is presented for their existence in solution state.