Model Studies of 6,7-Indolequinone Cofactors of Quinoprotein Amine Dehydrogenases

The electronic effects of the C-4 substituent on the physicochemical properties and reactivity of the
6,7-inodolequinone cofactors (CTQ and TTQ) have extensively been investigated with use of a series of
C-4 substituted 6,7-inodolequinone derivatives (1−4). The one-electron reduction potentials of the 6,7-inodolequinone derivatives decrease with increasing the electron donating ability of the C-4 substituent
(with the following order of E°‘:  4 > 1 > 2 > 3). The reaction of indolequinones 1−3 with benzylamine
proceeds stepwise through the iminoquinone and the product-imine intermediates to give aminophenol
as the final product as the case of TTQ model compound 4. The rate constants of each step have been
determined by the detailed kinetic analysis, and the kinetic deuterium isotope effects have also been
examined to confirm the rate-determining step. The reactivity of CTQ model compound 1 toward the
amines is by one order of magnitude lower than that of TTQ model compound 4. The reactivity of
indolequinones 2 and 3 is further decreased due to their stronger electron-donating substituents at C-4.
A more important difference between CTQ model compound 1 and TTQ model compound 4 is the
reactivity of the iminoquinone intermediate:  the reaction of the CTQ model compound with amines
stops at the iminoquinone formation stage at room temperature, whereas the reaction of the TTQ model
compound with amines proceeds up to the aminophenol formation. Thus, the energy barrier for the
rearrangement of the iminoquinone to the product-imine is higher in the CTQ model system than in the
TTQ model system.