Chemistry and Molecular Biology of Flavin in the "fully Reduced" State

In the history of flavin (bio)chemistry the "fully reduced state" (Flred) has drawn the least attention, as compared to the oxidized state ("flavoquinone," Flox ) and the radical state ("flavosemiquinone," FI). The reason for this is to be found not so much in the realm of science, but in the psychology of scientists: Flred does not exhibit an optical spectrum as distinctive as Flox , and even worse, it appears colorless to the eye in dilute solutions. Furthermore, unlike Flox , it does not fluoresce. Thirdly, it is extremely unstable towards O2. Fourthly, it is diamagnetic, unlike Fl. Hence, it does not seem to lend itself to "elegant" work. Quite in contrast to this superficial evaluation, the following becomes obvious upon somewhat more detailed inspection: (1) The absorption spectra in the visible and near-UV range of Flred are quite peculiar and call for structural interpretation. (2) The fact that Flred has the properties .of an "02-activator" renders it even more peculiar in view of its diamagnetism: Generally, the ground-state triplet species 02, chemically inert because of its highly symmetrical electron distribution, needs paramagnetic species for activation-i.e. heavy metal complexes, in order to facilitate intersystem crossing. The first researchers to assign a chemical structure to Flred were Kuhn and Weygand1 : They proposed 1,5-dihydroflavin as shown below. Since the reduction of Flox is thermodynamically reversible (cf. polarography2), we term 1,5-H2Flred "flavohydroquinone." Kuhn's assignment of the 1,5-H2Flred structure to "fully reduced flavin," though correct, seems more intuitive than experimentally founded, whereas the assignment of the FIH-structure as "l-monohydroflavin" proposed at the same time,I,3 proved ~o be incorrect.