Flavin 4a-hydroperoxide

The electron deficiency of the flavin 4a-hydroperoxide is enh mced by the electron-withdrawing isoalloxazine ring which increases its susceptibility to nucleophilic attack. N- and S-oxidation of amine and sulphides, respectively, occurs efficiently and 10 -10 times more effectively than using alkyl peroxides or hydrogen peroxide as the oxidant (Eqn. 28). 

The authors argue that flavin nitroxyl radical may play a role in flavo-enzyme chemistry and suggest that the nitroxyl radical intermediate may be derived from enzyme-bound flavin 4a-hydroperoxide. 

The deprotonated flavin in the complex is readily attacked by molecular oxygen at C4a, giving 4a-hydroperoxide of the flavin-luciferase complex (intermediate A). This complex is an unusually stable intermediate, with a lifetime of tens of seconds at 20°C and hours at subzero temperatures, allowing its isolation and characterization (Hastings et al., 1973 Tu, 1979 Balny and Hastings, 1975 Vervoort et al., 1986 Kurfuerst et al., 1987 Lee et al., 1988). 

Jones KC, Ballou DP. Reactions of the 4a-hydroperoxide of liver microsomal flavin-containing monooxygenase with nucleophilic and electrophilic substrates. J. Biol. Chem. 1986 261 2553-2559. 

The coordinated substrate reduces dioxygen, yielding a peroxy species that decomposes to the ring-opened product. Formation of the peroxy intermediate is analogous to the reaction of reduced flavin with oxygen to form tihe 4a-hydroperoxide , i.e. 

Scheme 57. Proposed mechanism of Anderson el al. involving homolytic scission of the flavin C(4a)-hydroperoxide bond (244).

Eckstein, J. W., Hastings, J. W., and Ghisla, S. (1993). Mechanism of bacterial bioluminescence. 4a,5-Dihydroflavin analogs as models for luciferase hydroperoxide intermediates and the effect of substituents at the 8-position of flavin on luciferase kinetics. Biochemistry 32 404 111. 

---