Comprehensive chiroptical study of proline-containing diamide compounds

Krisztina Knapp, Marcin Gõrecki, Jadwiga Frelek, Roman Luboradzki, Miklõs Hollõsi, Zsuzsa Majer, Elemér Vass

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Abstract

The continuously growing interest in the understanding of peptide folding led to the conformational investigation of methylamides of N-acetyl-amino acids as diamide models. Here we report the results of detailed conformational analysis on Ac-Pro-NHMe and Ac-β-HPro-NHMe diamides. These compounds were analyzed by experimental and computational methods, the conformational distributions obtained by Density Functional Theory (DFT) calculations for isolated and solvated diamide compounds are discussed. The conformational preference of proline-containing diamide compounds as a function of the ambience was observed by a number of chiroptical spectroscopic techniques, such as vibrational circular dichroism (VCD), electronic circular dichroism (ECD), Raman optical activity (ROA) spectroscopy, and additionally by single crystal X-ray diffraction analyses. Based on a comparison between Ac-Pro-NHMe and Ac-β-HPro-NHMe, one can conclude that due to the greater conformational freedom of the β-HPro derivative, Ac-β-HPro-NHMe shows different behavior in solid- and solution-phase, as well. Ac-β-HPro-NHMe tends to form cis Ac-β-HPro amide conformation in water, dichloromethane, and acetonitrile in contrast to its α-Pro analog. On the other hand, the crystal structure of the β-HPro compound cannot be related to any of the conformers obtained in vacuum and solution while the X-ray structure of Ac-Pro-NHMe was identified as tαL-, which is a trans Ac-Pro amide containing conformer also predominant in polar solvents. Chirality 26:228-242, 2014. © 2014 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)228-242
Number of pages15
JournalChirality
Volume26
Issue number4
DOIs
Publication statusPublished - Apr 2014

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Keywords

  • ECD
  • IR
  • ROA
  • Raman optical activity
  • VCD
  • conformational analysis
  • electronic circular dichroism
  • infrared spectroscopy
  • vibrational circular dichroism

ASJC Scopus subject areas

  • Analytical Chemistry
  • Catalysis
  • Pharmacology
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

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