Single-Conformation Spectroscopy of Capped Aminoisobutyric Acid Dipeptides: The Effect of C‑Terminal Cap Chromophores on Conformation

Aminoisobutyric
acid (Aib) oligomers are known to form racemic
mixtures of enantiomeric left- and right-handed structures. The introduction
of a chiral cap converts the enantiomeric structures into diastereomers
that, in principle, afford spectroscopic differentiation. Here, we
screen different C-terminal caps based on a model Aib dipeptide using
double resonance laser spectroscopy in the gas phase to record IR
and UV spectra of individual conformations present in the supersonic
expansion: NH-benzyl (NHBn) as a reference structure because of its
common use as a fluorophore in similar studies, NH-p-fluorobenzyl (NHBn-F), and α-methylbenzylamine (AMBA). For
both the NHBn and NHBn-F caps, a single conformer is observed, with
infrared spectra assignable to an enantiomeric pair of type II/II′
β-turns in these molecules lacking a chiral center. The higher
oscillator strength of the NHBn-F cap enabled UV–UV hole burning,
not readily accomplished with the NHBn cap. The AMBA-capped structure,
with its chiral center, produced two unique conformers, one of which
was a nearly identical left-handed type II β-turn, while the
minor conformer is assigned to a C7–C7 sequential double ring,
which is an emergent form of a 27-ribbon. Although not
observed, the type II′ β-turn diastereomer, with opposite
handedness, is calculated to be 11 kJ/mol higher in energy, a surprisingly
large difference. This destabilization is attributed primarily to
steric interference between the C-terminal acyl oxygen of the peptide
and the chirality-inducing methyl of the AMBA group. Last, computational
evidence indicates that the use of an N-terminal aromatic cap hinders
the formation of a 310-helix in Ac-Aib2 dipeptides.