Progress in the chemistry and molecular biology of flavine and flavocoenzymes

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. Further-more, unlike Flox, it does not fluoresce. Thirdly, it is extremely unstable to-wards 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 ob-vious 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 re-duction 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