Coenzyme Models. 47. Synthesis and Reactivity Studies of Novel Flavinophanes and 5-Deazaflavinophanes: Correlation between Flavin Reactivity and Ring Strain

Seiji Shinkai, Akito Kawase, Toshiro Yamaguchi, Osamu Manabe, Yoshikazu Wada, Fumio Yoneda, Yoshihisa Ohta, Kichisuke Nishimoto

Research output: Contribution to journalArticle

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Abstract

New flavinophanes Fl(n) and 5-deazaflavinophanes dFl(n) were synthesized in which N(3) and O(2′) in the 10-(2-hydroxyphenyl) group were linked by a -(CH2)n- chain (n = 6, 7, 8, 10, and 12). In the lH NMR spectra the chemical shift of 9-H in the isoalloxazine ring and 6'-H in the 10-phenyl ring moved to lower magnetic field with decreasing ring size. The change corresponds to the decrease in the dihedral angle between the isoalloxazine ring and the 10-phenyl ring. The NOE (nuclear Overhauser effect) measurement also supported that the distance between 9-H and 6'-H decreases with decreasing ring size. X-ray crystallographic studies of dFl(6) established that the dihedral angle (θ) between the isoalloxazine ring and the 10-phenyl ring is 76.5°, considerably smaller than the 90° that minimizes the steric crowding of conventional 10-phenylisoalloxazine derivatives. The ab initio MO calculation of 10-phenylisoalloxazine indicates that the equilibrium geometry is such that θ = 60-90° and Fl(n) and dFl(n), with the smaller θ, are destabilized because of steric hindrance. The steric strain induced by the short ring strap is reflected by the reactivities of Fl(n) and dFl(n): For the oxidation of 1-benzyl-1,4-dihydronicotinamide (BNAH), sterically strained Fl(6) and dFl(6) have rate constants 11 and 16 times greater than those for Fl(12) and dFl(12). For the reversible 5-adduct formation between Fl(n) and SO32-, kf (forward reaction) for Fl(6) is greater by a factor of 5.2 than that for Fl(12), while kr (reverse reaction) for Fl(6) is smaller by a factor of 3.6 than that for Fl(12). These results can be explained by destabilization of the initial state due to steric strain induced by the ring strap.

Original languageEnglish
Pages (from-to)4928-4935
Number of pages8
JournalJournal of the American Chemical Society
Volume111
Issue number13
DOIs
Publication statusPublished - Jan 1 1989
Externally publishedYes

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Coenzymes
Dihedral angle
Chemical shift
Rate constants
Nuclear magnetic resonance
Magnetic Fields
Magnetic fields
Derivatives
X rays
Oxidation
Geometry
X-Rays
4,6-dinitro-o-cresol
isoalloxazine

All Science Journal Classification (ASJC) codes

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

Cite this

Coenzyme Models. 47. Synthesis and Reactivity Studies of Novel Flavinophanes and 5-Deazaflavinophanes : Correlation between Flavin Reactivity and Ring Strain. / Shinkai, Seiji; Kawase, Akito; Yamaguchi, Toshiro; Manabe, Osamu; Wada, Yoshikazu; Yoneda, Fumio; Ohta, Yoshihisa; Nishimoto, Kichisuke.

In: Journal of the American Chemical Society, Vol. 111, No. 13, 01.01.1989, p. 4928-4935.

Research output: Contribution to journalArticle

Shinkai, Seiji ; Kawase, Akito ; Yamaguchi, Toshiro ; Manabe, Osamu ; Wada, Yoshikazu ; Yoneda, Fumio ; Ohta, Yoshihisa ; Nishimoto, Kichisuke. / Coenzyme Models. 47. Synthesis and Reactivity Studies of Novel Flavinophanes and 5-Deazaflavinophanes : Correlation between Flavin Reactivity and Ring Strain. In: Journal of the American Chemical Society. 1989 ; Vol. 111, No. 13. pp. 4928-4935.
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abstract = "New flavinophanes Fl(n) and 5-deazaflavinophanes dFl(n) were synthesized in which N(3) and O(2′) in the 10-(2-hydroxyphenyl) group were linked by a -(CH2)n- chain (n = 6, 7, 8, 10, and 12). In the lH NMR spectra the chemical shift of 9-H in the isoalloxazine ring and 6'-H in the 10-phenyl ring moved to lower magnetic field with decreasing ring size. The change corresponds to the decrease in the dihedral angle between the isoalloxazine ring and the 10-phenyl ring. The NOE (nuclear Overhauser effect) measurement also supported that the distance between 9-H and 6'-H decreases with decreasing ring size. X-ray crystallographic studies of dFl(6) established that the dihedral angle (θ) between the isoalloxazine ring and the 10-phenyl ring is 76.5°, considerably smaller than the 90° that minimizes the steric crowding of conventional 10-phenylisoalloxazine derivatives. The ab initio MO calculation of 10-phenylisoalloxazine indicates that the equilibrium geometry is such that θ = 60-90° and Fl(n) and dFl(n), with the smaller θ, are destabilized because of steric hindrance. The steric strain induced by the short ring strap is reflected by the reactivities of Fl(n) and dFl(n): For the oxidation of 1-benzyl-1,4-dihydronicotinamide (BNAH), sterically strained Fl(6) and dFl(6) have rate constants 11 and 16 times greater than those for Fl(12) and dFl(12). For the reversible 5-adduct formation between Fl(n) and SO32-, kf (forward reaction) for Fl(6) is greater by a factor of 5.2 than that for Fl(12), while kr (reverse reaction) for Fl(6) is smaller by a factor of 3.6 than that for Fl(12). These results can be explained by destabilization of the initial state due to steric strain induced by the ring strap.",
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T2 - Correlation between Flavin Reactivity and Ring Strain

AU - Shinkai, Seiji

AU - Kawase, Akito

AU - Yamaguchi, Toshiro

AU - Manabe, Osamu

AU - Wada, Yoshikazu

AU - Yoneda, Fumio

AU - Ohta, Yoshihisa

AU - Nishimoto, Kichisuke

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N2 - New flavinophanes Fl(n) and 5-deazaflavinophanes dFl(n) were synthesized in which N(3) and O(2′) in the 10-(2-hydroxyphenyl) group were linked by a -(CH2)n- chain (n = 6, 7, 8, 10, and 12). In the lH NMR spectra the chemical shift of 9-H in the isoalloxazine ring and 6'-H in the 10-phenyl ring moved to lower magnetic field with decreasing ring size. The change corresponds to the decrease in the dihedral angle between the isoalloxazine ring and the 10-phenyl ring. The NOE (nuclear Overhauser effect) measurement also supported that the distance between 9-H and 6'-H decreases with decreasing ring size. X-ray crystallographic studies of dFl(6) established that the dihedral angle (θ) between the isoalloxazine ring and the 10-phenyl ring is 76.5°, considerably smaller than the 90° that minimizes the steric crowding of conventional 10-phenylisoalloxazine derivatives. The ab initio MO calculation of 10-phenylisoalloxazine indicates that the equilibrium geometry is such that θ = 60-90° and Fl(n) and dFl(n), with the smaller θ, are destabilized because of steric hindrance. The steric strain induced by the short ring strap is reflected by the reactivities of Fl(n) and dFl(n): For the oxidation of 1-benzyl-1,4-dihydronicotinamide (BNAH), sterically strained Fl(6) and dFl(6) have rate constants 11 and 16 times greater than those for Fl(12) and dFl(12). For the reversible 5-adduct formation between Fl(n) and SO32-, kf (forward reaction) for Fl(6) is greater by a factor of 5.2 than that for Fl(12), while kr (reverse reaction) for Fl(6) is smaller by a factor of 3.6 than that for Fl(12). These results can be explained by destabilization of the initial state due to steric strain induced by the ring strap.

AB - New flavinophanes Fl(n) and 5-deazaflavinophanes dFl(n) were synthesized in which N(3) and O(2′) in the 10-(2-hydroxyphenyl) group were linked by a -(CH2)n- chain (n = 6, 7, 8, 10, and 12). In the lH NMR spectra the chemical shift of 9-H in the isoalloxazine ring and 6'-H in the 10-phenyl ring moved to lower magnetic field with decreasing ring size. The change corresponds to the decrease in the dihedral angle between the isoalloxazine ring and the 10-phenyl ring. The NOE (nuclear Overhauser effect) measurement also supported that the distance between 9-H and 6'-H decreases with decreasing ring size. X-ray crystallographic studies of dFl(6) established that the dihedral angle (θ) between the isoalloxazine ring and the 10-phenyl ring is 76.5°, considerably smaller than the 90° that minimizes the steric crowding of conventional 10-phenylisoalloxazine derivatives. The ab initio MO calculation of 10-phenylisoalloxazine indicates that the equilibrium geometry is such that θ = 60-90° and Fl(n) and dFl(n), with the smaller θ, are destabilized because of steric hindrance. The steric strain induced by the short ring strap is reflected by the reactivities of Fl(n) and dFl(n): For the oxidation of 1-benzyl-1,4-dihydronicotinamide (BNAH), sterically strained Fl(6) and dFl(6) have rate constants 11 and 16 times greater than those for Fl(12) and dFl(12). For the reversible 5-adduct formation between Fl(n) and SO32-, kf (forward reaction) for Fl(6) is greater by a factor of 5.2 than that for Fl(12), while kr (reverse reaction) for Fl(6) is smaller by a factor of 3.6 than that for Fl(12). These results can be explained by destabilization of the initial state due to steric strain induced by the ring strap.

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