Conformer-Specific and Diastereomer-Specific Spectroscopy of αβα Synthetic Foldamers: Ac-Ala-βACHC-Ala-NHBn

Karl N. Blodgett, Xiao Zhu, Patrick S. Walsh, Dewei Sun, Jaeyeon Lee, Soo Hyuk Choi, Timothy S. Zwier

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The folding propensities of a capped, cyclically constrained, mixed α/β diastereomer pair, (SRSS) Ac-Ala-βACHC-Ala-NHBn (hereafter RS) and (SSRS) Ac-Ala-βACHC-Ala-NHBn (SR), have been studied in a molecular beam using single-conformation spectroscopic techniques. These α/β-tripeptides contain a cyclohexane ring across each Cα-Cβ bond, at which positions their stereochemistries differ. This cyclic constraint requires any stable species to adopt one of two ACHC configurations: equatorial C?O/axial NH or equatorial NH/axial C?O. Resonant two-photon ionization (R2PI) and infrared-ultraviolet hole-burning (IR-UV HB) spectroscopy were used in the S0-S1 region of the UV chromophore, revealing the presence of three unique conformational isomers of RS and two of SR. Resonant ion-dip infrared spectra were recorded in both the NH stretch (3200-3500 cm-1) and the amide I (1600-1800 cm-1) regions. These experimental vibrational frequencies were compared with the scaled calculated normal-mode frequencies from density functional theory at the M05-2X/6-31+G(d) level of theory, leading to structural assignments of the observed conformations. The RS diastereomer is known in crystalline form to preferentially form a C11/C9 mixed helix, in which alternating hydrogen bonds are arranged in near antiparallel orientation. This structure is preserved in one of the main conformers observed in the gas phase but is in competition with both a tightly folded C7eq/C12/C8/C7eq structure, in which all four amide NH groups and four C?O groups are engaged in hydrogen bonding, as well as a cap influenced C7eq/NH···π/C11 structure. The SR diastereomer is destabilized by inducing backbone dihedral angles that lie outside the typical Ramachandran angles. This diastereomer also forms a C11/C9 mixed helix as well as a cap influenced bifurcated C7ax-C11/NH···π/C7eq structure as the global energy minimum. Assigned structures are compared with the reported crystal structure of analogous α/β-tripeptides, and disconnectivity graphs are presented to give an overview of the complicated potential energy surface of this tripeptide diastereomer pair.

Original languageEnglish
Pages (from-to)3697-3710
Number of pages14
JournalJournal of Physical Chemistry A
Volume122
Issue number14
DOIs
Publication statusPublished - 2018 Apr 12

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caps
Amides
helices
amides
Conformations
Hydrogen bonds
Spectroscopy
Infrared radiation
Potential energy surfaces
Stereochemistry
Molecular beams
stereochemistry
hole burning
Vibrational spectra
Dihedral angle
Chromophores
Isomers
cyclohexane
folding
spectroscopy

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry

Cite this

Blodgett, Karl N. ; Zhu, Xiao ; Walsh, Patrick S. ; Sun, Dewei ; Lee, Jaeyeon ; Choi, Soo Hyuk ; Zwier, Timothy S. / Conformer-Specific and Diastereomer-Specific Spectroscopy of αβα Synthetic Foldamers : Ac-Ala-βACHC-Ala-NHBn. In: Journal of Physical Chemistry A. 2018 ; Vol. 122, No. 14. pp. 3697-3710.
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title = "Conformer-Specific and Diastereomer-Specific Spectroscopy of αβα Synthetic Foldamers: Ac-Ala-βACHC-Ala-NHBn",
abstract = "The folding propensities of a capped, cyclically constrained, mixed α/β diastereomer pair, (SRSS) Ac-Ala-βACHC-Ala-NHBn (hereafter RS) and (SSRS) Ac-Ala-βACHC-Ala-NHBn (SR), have been studied in a molecular beam using single-conformation spectroscopic techniques. These α/β-tripeptides contain a cyclohexane ring across each Cα-Cβ bond, at which positions their stereochemistries differ. This cyclic constraint requires any stable species to adopt one of two ACHC configurations: equatorial C?O/axial NH or equatorial NH/axial C?O. Resonant two-photon ionization (R2PI) and infrared-ultraviolet hole-burning (IR-UV HB) spectroscopy were used in the S0-S1 region of the UV chromophore, revealing the presence of three unique conformational isomers of RS and two of SR. Resonant ion-dip infrared spectra were recorded in both the NH stretch (3200-3500 cm-1) and the amide I (1600-1800 cm-1) regions. These experimental vibrational frequencies were compared with the scaled calculated normal-mode frequencies from density functional theory at the M05-2X/6-31+G(d) level of theory, leading to structural assignments of the observed conformations. The RS diastereomer is known in crystalline form to preferentially form a C11/C9 mixed helix, in which alternating hydrogen bonds are arranged in near antiparallel orientation. This structure is preserved in one of the main conformers observed in the gas phase but is in competition with both a tightly folded C7eq/C12/C8/C7eq structure, in which all four amide NH groups and four C?O groups are engaged in hydrogen bonding, as well as a cap influenced C7eq/NH···π/C11 structure. The SR diastereomer is destabilized by inducing backbone dihedral angles that lie outside the typical Ramachandran angles. This diastereomer also forms a C11/C9 mixed helix as well as a cap influenced bifurcated C7ax-C11/NH···π/C7eq structure as the global energy minimum. Assigned structures are compared with the reported crystal structure of analogous α/β-tripeptides, and disconnectivity graphs are presented to give an overview of the complicated potential energy surface of this tripeptide diastereomer pair.",
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Conformer-Specific and Diastereomer-Specific Spectroscopy of αβα Synthetic Foldamers : Ac-Ala-βACHC-Ala-NHBn. / Blodgett, Karl N.; Zhu, Xiao; Walsh, Patrick S.; Sun, Dewei; Lee, Jaeyeon; Choi, Soo Hyuk; Zwier, Timothy S.

In: Journal of Physical Chemistry A, Vol. 122, No. 14, 12.04.2018, p. 3697-3710.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Conformer-Specific and Diastereomer-Specific Spectroscopy of αβα Synthetic Foldamers

T2 - Ac-Ala-βACHC-Ala-NHBn

AU - Blodgett, Karl N.

AU - Zhu, Xiao

AU - Walsh, Patrick S.

AU - Sun, Dewei

AU - Lee, Jaeyeon

AU - Choi, Soo Hyuk

AU - Zwier, Timothy S.

PY - 2018/4/12

Y1 - 2018/4/12

N2 - The folding propensities of a capped, cyclically constrained, mixed α/β diastereomer pair, (SRSS) Ac-Ala-βACHC-Ala-NHBn (hereafter RS) and (SSRS) Ac-Ala-βACHC-Ala-NHBn (SR), have been studied in a molecular beam using single-conformation spectroscopic techniques. These α/β-tripeptides contain a cyclohexane ring across each Cα-Cβ bond, at which positions their stereochemistries differ. This cyclic constraint requires any stable species to adopt one of two ACHC configurations: equatorial C?O/axial NH or equatorial NH/axial C?O. Resonant two-photon ionization (R2PI) and infrared-ultraviolet hole-burning (IR-UV HB) spectroscopy were used in the S0-S1 region of the UV chromophore, revealing the presence of three unique conformational isomers of RS and two of SR. Resonant ion-dip infrared spectra were recorded in both the NH stretch (3200-3500 cm-1) and the amide I (1600-1800 cm-1) regions. These experimental vibrational frequencies were compared with the scaled calculated normal-mode frequencies from density functional theory at the M05-2X/6-31+G(d) level of theory, leading to structural assignments of the observed conformations. The RS diastereomer is known in crystalline form to preferentially form a C11/C9 mixed helix, in which alternating hydrogen bonds are arranged in near antiparallel orientation. This structure is preserved in one of the main conformers observed in the gas phase but is in competition with both a tightly folded C7eq/C12/C8/C7eq structure, in which all four amide NH groups and four C?O groups are engaged in hydrogen bonding, as well as a cap influenced C7eq/NH···π/C11 structure. The SR diastereomer is destabilized by inducing backbone dihedral angles that lie outside the typical Ramachandran angles. This diastereomer also forms a C11/C9 mixed helix as well as a cap influenced bifurcated C7ax-C11/NH···π/C7eq structure as the global energy minimum. Assigned structures are compared with the reported crystal structure of analogous α/β-tripeptides, and disconnectivity graphs are presented to give an overview of the complicated potential energy surface of this tripeptide diastereomer pair.

AB - The folding propensities of a capped, cyclically constrained, mixed α/β diastereomer pair, (SRSS) Ac-Ala-βACHC-Ala-NHBn (hereafter RS) and (SSRS) Ac-Ala-βACHC-Ala-NHBn (SR), have been studied in a molecular beam using single-conformation spectroscopic techniques. These α/β-tripeptides contain a cyclohexane ring across each Cα-Cβ bond, at which positions their stereochemistries differ. This cyclic constraint requires any stable species to adopt one of two ACHC configurations: equatorial C?O/axial NH or equatorial NH/axial C?O. Resonant two-photon ionization (R2PI) and infrared-ultraviolet hole-burning (IR-UV HB) spectroscopy were used in the S0-S1 region of the UV chromophore, revealing the presence of three unique conformational isomers of RS and two of SR. Resonant ion-dip infrared spectra were recorded in both the NH stretch (3200-3500 cm-1) and the amide I (1600-1800 cm-1) regions. These experimental vibrational frequencies were compared with the scaled calculated normal-mode frequencies from density functional theory at the M05-2X/6-31+G(d) level of theory, leading to structural assignments of the observed conformations. The RS diastereomer is known in crystalline form to preferentially form a C11/C9 mixed helix, in which alternating hydrogen bonds are arranged in near antiparallel orientation. This structure is preserved in one of the main conformers observed in the gas phase but is in competition with both a tightly folded C7eq/C12/C8/C7eq structure, in which all four amide NH groups and four C?O groups are engaged in hydrogen bonding, as well as a cap influenced C7eq/NH···π/C11 structure. The SR diastereomer is destabilized by inducing backbone dihedral angles that lie outside the typical Ramachandran angles. This diastereomer also forms a C11/C9 mixed helix as well as a cap influenced bifurcated C7ax-C11/NH···π/C7eq structure as the global energy minimum. Assigned structures are compared with the reported crystal structure of analogous α/β-tripeptides, and disconnectivity graphs are presented to give an overview of the complicated potential energy surface of this tripeptide diastereomer pair.

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U2 - 10.1021/acs.jpca.8b01273

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