jp0c03545_si_001.pdf (3.53 MB)
Coexistence of Left- and Right-Handed 12/10-Mixed Helices in Cyclically Constrained β‑Peptides and Directed Formation of Single-Handed Helices upon Site-Specific Methylation
journal contribution
posted on 2020-07-02, 18:37 authored by Karl N. Blodgett, Geunhyuk Jang, Sojung Kim, Min Kyung Kim, Soo Hyuk Choi, Timothy S. ZwierThe
inherent conformational preferences of the neutral β–peptide
foldamer series, Ac-(ACHC)n-NHBn, n = 2–4, are studied in the gas phase using conformation-specific
IR–UV double resonance methods. The cyclically constrained
chiral β-amino acid cis-2-aminocyclohexane
carboxylic acid (ACHC) is designed to bring both right- and left-handed
helices into close energetic proximity. Comparison of the infrared
spectra in the NH stretch and amide I/II regions with the predictions
of DFT calculations lead to the unambiguous assignment of four out
of the six observed conformations of the molecules in this series,
while corroborating computational and spectral evidence, affords tentative
assignments of the remaining two conformers for which IR data were
not recorded. The observed structures fall into one of two conformational
families: a right-handed 12/10-mixed helix or its “cap-disrupted”
left-handed helical analogue, which coexist with significant populations.
Site-specific and stereospecific methylation on the cyclohexane backbone
at the dipeptide (n = 2) level is also tested as
a means to sterically lock in a predetermined cyclohexane chair conformation.
These substitutions are proven to be a means of selectively driving
formation of one helical screw sense or the other. Calculated relative
energies and free energies of all possible structures for the molecules
provide strong supporting evidence that the rigid nature of the ACHC
residue confers unusual stability to the 12/10-mixed helix conformation,
regardless of local environment, temperature, or C-terminal capping
unit. The simultaneous presence of both handed helices offers unique
opportunities for future studies of their interconversion.
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Site-Specific Methylationstereospecific methylationIR datahelical analogueseriesNH stretchhelix conformationacid cis -2- aminocyclohexane carbo...Single-Handed Helicesfuture studiesgas phaseACHC residueresonance methodschiral β-heliceevidencecyclohexane backbonehelical screw senseDFT calculationsassignmentmoleculecyclohexane chair conformationstructures fall
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