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By sulfur substitution of the N-5 atom in flavins and flavocoenzymes a flavin analog is obtained, 5-thiaflavin, which is found to be isoelectronic and isosteric with natural flavin in the fully reduced and half-reduced states, but not in the oxidized state. Among the three 'redox shuttles' characterizing the flavin system, viz. upper 1e-, lower 1e- and 2e- shuttle, only the second one is retained in thiaflavin, which limits the redox activity of this system to 1e- transfer. The structure and properties of the molecular species participating in the thiaflavin redox system are discussed in comparison with the flavin system. The corresponding chemistry of a '2e- flavin', 5-deazaflavin, has been treated in the preceding paper. 5-Thiaflavin is found to exhibit a stable neutral radical, which is analogous to the 'blue' flavosemiquinone. Unlike normal flavin, where the radical is in a dismutation equilibrium, thiaflavin radical shows reversible formation of a covalent dimer, which is stable in aprotic solution and disproportionates only in water, with irreversible formation of a sulfoxide. The ultraviolet and infrared spectra of the dimer are in agreement with the structure of two 5-thiaflavin molecules linked covalently at their 4a carbons. This corroborates the earlier hypothesis that the essential intermediate in the dismutation of normal flavin is likewise a covalent dimer. Thiaflavin is tightly bound by apoflavodoxin. The protein catalyses the autoxidation to the radical state. Thiaflavodoxin radical is even more stable (towards further oxidation) than is the free thiaflavin radical. The redox potential of the couple reduced thiaflavin/thiaflavin radical (sFlred/sFl) is surprisingly high. From the reversible equilibrium established with ferricyanide, sFlred + Fe(CN)63- ⇄ sFl• + Fe(CN)64-, the standard potential of the sFlred/sFl• couple, Em at pH 7, has been estimated as + 0.38 V. [ABSTRACT FROM AUTHOR]