1,5-dihydroflavin anion

The peroxy-anion transfer reaction of Equation 45 has been established (51). This finding was intriguing because we had shown previously that FlEt- reacts with molecular oxygen to provide 4a-FlEtOO" (Equation 37). Combination of Equations 37 and 45 yields Equation 46, establishing that the dihydroflavin anion is a catalyst for the reaction of oxygen with the phenolate ion. 

N(l) is the site of strongest basicity, but not of strongest nucleo-philicity in the dihydroflavin anion HFEed- This is due to steric hindrance by the peri-substituent at N(10). This hindrance can only be overcome in the case of m/ramolecular N(l)-alkylation, e.g. (66) ... 

Unsubstituted dihydroflavin-anions might, as has been stated previously, be considered as Flavin-hydride complexes , though one might infer that the term complex is abused if used in this way. In fact there are two ways to define the term complex . Historically, this term means that one does not know how to explain the structure of a given species in terms of chemical bonds. Nowadays, however, pure chemistry attempts to comprehend practically everything, including Amor and Psyche, in terms of chemical bonds, and the term complex is confined, in pure chemistry, to a species in which the coordination number of the central atom exceeds its oxidation number. In bio-... 

Flavin coenzymes can exist in any of three different redox states. Fully oxidized flavin is converted to a semiqulnone by a one-electron transfer, as shown in Figure 18.22. At physiological pH, the semiqulnone is a neutral radical, blue in color, with a A ax of 570 nm. The semiqulnone possesses a pAl of about 8.4. When it loses a proton at higher pH values, it becomes a radical anion, displaying a red color with a A ax of 490 nm. The semiqulnone radical is particularly stable, owing to extensive delocalization of the unpaired electron across the 77-electron system of the isoalloxazine. A second one-electron transfer converts the semiqulnone to the completely reduced dihydroflavin as shown in Figure 18.22. 

Reduction of flavin by two electrons yields the 1,5-dihydroflavin (Scheme 3), often called reduced flavin . Since isomeric two-electron reduced flavin structures are known (cf. below), the term reduced flavin should be avoided unless defined to prevent misunderstanding. From all flavin species possible in a redox reaction the solution of 1,5-dihydroflavin is, in contrast to that of some isomeric compounds, devoid of a stront colour but not colourless as indicated by the term leucoflavin , which is still used (Table 4). The only true colourless species is (77). Because of the very high oxygen-sensitivity of 1,5-dihydroflavin its chemical and physical properties were investigated only recently Long before crystallographic data on flavins were available, conclusions were drawn from the molar extinction coefficient at 450 nm of 1,5-dihydroflavins with respect to the planarity of the molecules. From the data presented in Table 5 it was proposed that anionic... 

Molecular oxygen usually reacts rapidly with only those organic substrates, such as dihydroflavins, that are able to form stable free radicals. However, the endiolate anion of Eq. 13-50 may be able to donate a single electron to 02 to form a superoxide-organic radical pair prior to formation of the peroxide (see also Eq. 15-30). Similar oxygenase side reactions have been observed for a variety of other enzymes that utilize carbanion mechanisms.283 The reaction of rubisco with 02 is of both theoretical and practical interest, the latter because of its significance in lowering the yield in photosynthesis (Chapter 23). 

With 1,2-diphenylhydrazine (PhNHNHPh), the azobenzene anion radical is rapidly oxidized by dioxygen to azobenzene, which also is true for the phenazine and lumi-flavin anion radicals. Hence, 02 acts as an initiator for the autoxidation of these compounds (equation 153). For 1,2-diphenylhydrazine, turnover numbers in excess of 200 substrate molecules per 02 have been observed. The 1,2-diphenylhydrazine autoxidation cycle can be initiated by HO , which indicates that 02 is formed in the HO initiated process. Superoxide ion also initiates the autoxidation of dihydrophenazine, which is a model for dihydroflavin. For example, the addition of 1 mM (Me4N)02 in DMF to 10 mM H2Phen in an 02-saturated DMF solution results in the complete oxidation of the substrate (about 80% recovered as phenazine) and the production of 9 -10 mM HOOH. 

Thiols may be oxidised to disulphides by the intermediate formation of covalent 4a flavin-sulphur adducts subsequent nucleophilic attack by another thiol anion displaces dihydroflavin as a good leaving group (XXXXIV). 

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