Determination of 3JHF and 4JHF Karplus Relationships for the Ø and ѱ Angles of Peptides Using N-Fluoroamides as Models

Charles F. Hammer, Srinivasan Chandrasegaran

Research output: Contribution to journalArticlepeer-review

Abstract

A series of N-fluoroamide derivatives were synthesized by the reaction of CF3OF with the corresponding amides. The reaction procedure of Barton et al.1 was appropriately modified to maximize the yield of the pure monofluoro derivatives. The compounds were examined as models for the determination of the Ø′ (3Jhf) and ѱ′ (4JHF) angles of peptides with 1H, 19F, and 13C NMR spectroscopy. Investigation of this series of compounds has led to Karplus-type relations between Ø′ vs. 3JHF and ѱ vs. 4JHF using the experimental coupling constants. As the signs of the coupling constants could not be determined at this time, several possibilities arise for these relations. Of these, the fitted equation (R = 0.990), 3JNF-CH = 70.8 cos2 Ø′ − 44.1 cos Ø′ − 7.2, best describes the angular relation for the Ø′ angle. The fitted equation (R = 0.983), 4JNF-CO-CH = −19.5 cos2 ѱ + 8.8 cos ѱ + 4.9, best describes the angular relation for the ѱ′ angle. The plots of both equations give typical Karplus curves except that they go through zero, i.e., undergo an inversion of sign. Fluorination of the amides causes the chemical shift of the carbonyl carbon to be shifted upfield 4–5 ppm while the carbon α to the nitrogen is shifted downfield 7–12 ppm. Furthermore, these carbons appear as doublets (2Jc-nf = 4-9 Hz for the CᆖO and <1.0–14.7 Hz for Cα) because of their coupling with the fluorine atom. The 19F chemical shifts of the model N-fluoroamide derivatives vary more than 39 ppm (δF 42 to 81 downfield of external CFC13) and are very sensitive to structural changes. It was not possible, however, to observe less than 5-Hz couplings in the 19F spectra because of the quadrupolar broadening caused by the 14N atom.

Original languageEnglish (US)
Pages (from-to)1543-1552
Number of pages10
JournalJournal of the American Chemical Society
Volume106
Issue number6
DOIs
StatePublished - Mar 1 1984

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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