Coenzyme Models. 31. Efficient Trapping of Transient Thiazolium-Aldehyde Adducts (Active Aldehydes) by Intramolecular and Quasi-Intramolecular Flavins. Flavin-Thiamin Biscoenzyme

Seiji Shinkai, Takaharu Yamashita, Yumiko Kusano, Osamu Manabe

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The reaction sequence of acyloin condensation of aldehydes, catalyzed by thiazolium ion bound to the CTAB micelle, can be diverted by the addition of flavin to the oxidation reaction to afford the corresponding carboxylic acids. It was found, however, that when the aldehyde concentration is elevated or the aldehyde is relatively reactive, intermolecular flavin (3-methyltetra-O-acetylriboflavin, MeFl) cannot trap the intermediates (active aldehydes) formed from thiazolium ion and aldehydes completely, leading to a competition between the conventional acyloin condensation and the flavin oxidation. We have applied the concept of intramolecular catalysis to this system by two methods in order to suppress the acyloin condensation relative to the flavin oxidation. The first utilizes quasi-intramolecular flavin oxidation in which hydrophobic 10-dodecylisoalloxazine (10-DodFl) and N-hexadecylthiazolium bromide (HxdT) are bound to a CTAB micelle aggregate. The second is a flavinthiazolium biscoenzyme (Fl-T) oxidation in which the intermediates on the thiazolium moiety are oxidized efficiently by the intramolecular flavin. When 4-chlorobenzaldehyde (100 mM) was employed as substrate, the trapping efficiency (=flavin oxidation product/sum of acyloin condensation products) for MeFl was 1.6. The trapping efficiency for the quasi-intramolecular flavin oxidation was improved up to 15–33-fold owing to the enhanced local concentration of 10-DodFl in the micelle phase; efficiency for the biscoenzyme system was further enhanced (>115-fold). A kinetic examination has established that the reaction is zero order in MeFl for the intermolecular flavin oxidation of 4-chlorobenzaldehyde, whereas it becomes first order in MeFl for the oxidation of more reactive pyridine-4-carboxaldehyde (pyCHO). This indicates that the rate-limiting step changes depending on the reactivity of aldehyde: the deprotonation from the thiazolium-aldehyde adduct is rate limiting in the oxidation of 4-chlorobenzaldehyde, whereas the oxidation of the deprotonated active aldehyde by MeFl becomes rate limiting in the oxidation of pyCHO. On the other hand, quasi-intramolecular flavin oxidation of pyCHO was zero order in 10-DodFl at low pyCHO concentrations (<10 mM) and was approximated by a first-order equation at high pyCHO concentrations (>50 mM). In the biscoenzyme oxidation of pyCHO, the zero-order decrease was always observed for up to 60% reaction, indicating the high efficiency of intramolecular flavin as a trapping agent. The present system is a relevant model for pyruvate oxidase which requires FAD and thiamine pyrophosphate as cofactors and catalyzes the convension of pyruvic acid to acetic acid.

Original languageEnglish
Pages (from-to)563-568
Number of pages6
JournalJournal of the American Chemical Society
Volume104
Issue number2
DOIs
Publication statusPublished - Jan 1 1982
Externally publishedYes

All Science Journal Classification (ASJC) codes

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

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