Flavin radical anion

Flavin radical anion Neutral flavin radical... 

One-electron transfer from the substrate amino group to flavin (FI) results in the formation of the aminium radical and the flavin radical anion (FC) (Scheme 15). Deprotonation of the aminium radical to yield an a-aminoalkyl radical followed by a second electron transfer to the flavin radical anion will result in the formation of the reduced flavin and iminium ion. Alternatively the iminium ion can be formed by path d in Scheme 15 this involves formation of a covalent adduct which can... 

Electron transfer from the amine to flavin would result in the aminium radical which is expected to rearrange rapidly to radical 61. Inactivation of the enzyme would then occur via coupling of the radical with the flavin radical anion resulting in the formation of 66. Coupling of the aminium radical with an amino acid radical would result in the formation of 65. By use of radioactive labeling techniques Silverman et al. have confirmed the formation of 65 and 66 this confirms the role of electron transfer in the oxidation process. Similar studies have been performed using 1-phenylcyclobutylamine (Scheme 18) [198]. 

Breilinger, E. Niemz. A. Rotello. V.M. Model systems for tlavoenzyme activity. Stabilization of the flavin radical anion through specific hydrogen bond interactions. J. Am. Chem. Soc. 1995, 117, 5379. 

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. 

The reactions most commonly involved in flavin redox chemistry are shown in Equations 1.15-1.17. One-electron reduction of the flavin (Eq. 1.15) produces a relatively stable radical anion. Protonation of the radical anion produces an unstable neutral radical (Eq. 1.16), which will be rapidly reduced by another electron (Eq. 1.17) to give the flavohydroquinone anion. 

The absorption spectral properties of the neutral and anionic forms are quite different as shown in Fig. 1. Due to the rapid dismutation of flavin radicals to form an equilibrium mixture with the hydroquinone and oxidized forms of the flavin, special procedures must be employed to measure the spectral properties of free flavin radicals. Nearly quantitative amounts of anion radical can be formed in aprotic solvents under basic conditions Alkylation of the N(5) position of the flavin hydroquinone followed by oxidation results in nearly quantitative formation of the... 

The model system studies of Muller et al. have shown that alkylation of the 0(2) and 0(4) positions of the isolloxazine ring results in a flavin radical with similar ESR and absorption spectral properties as the anion flavin radicals although this flavin species has a neutral charge. Whereas binding of the flavin to its site on... 

Neutral flavin radicals have a blue color (the wavelength of the absorption maximum, A.max, is -560 nm) but either protonation at N-l or dissociation of a proton from N-5 leads to red cation or anion radicals with imax at -477 nm. Both blue and red radicals are... 

The reaction is more complex than it appears. As soon as a small amount of oxidized flavin is formed, it reacts with reduced flavin to generate flavin radicals F1H (Eq. 15-27). The latter react rapidly with 02 each donating an electron to form superoxide anion radicals 02 (Eq. 15-30a) which can then combine with flavin radicals (Eq. 15-30b).284... 

Aprotic solvents mimic the hydrophobic protein interior. However, a functional artificial receptor for flavin binding under physiological conditions must be able to interact with the guest even in competitive solvents. As found by spectroscopic measurements with phenothiazene-labeled cyclene, the coordinative bond between flavin and Lewis-acidic macrocyclic zinc in methanol was strong enough for this function. Stiochiometry of the complex was proved by Job s plot analysis. Redox properties of the assemblies in methanol were studied by cyclic voltammetry which showed that the binding motif allowed interception of the ECE reduction mechanism and stabilisation of a flavosemiquinone radical anion in a polar solvent. As a consequence, the flavin chromophore switched from a two-electron-one-step process to a two-step-one-electron-each by coordination. 

The neutral flavin radical has an absorption maximum at 580 nm and hence a blue color it is sometimes referred to as the blue radical. It can undergo either protonation atN-1 to yield a cation radical or deprotonation atN-5 to yield an anion radical, if the enzyme has appropriate proton donating or withdrawing amino acid residues at the catalytic site. Both protonation and deprotonation result in the same spectral shift to give an absorption maximum at 470 nm and hence a red color. Both the blue and red radicals are seen as intermediates in enzyme reactions, suggesting that some enzymes form the neutral radical, whereas others form one of the charged radicals. 

Almost all biological tissues contain some organic free radicals that are detectable by ESR. These radicals ( tissue radicals ) are of low reactivity in the sense that they do not react readily with molecules in the system, in particular oxygen if this is present. Thus, they tend to be radicals at the end of a radical chain. Examples are the ascorbate radical anion, melanin free radicals, and some other oxygen-insensitive species, such as some flavin semiquinones. The magnetic properties of these various radicals are sufficiently distinct that their ESR spectra can be differentiated on the basis of g value and linewidth. 

Based on the known chemistry of flavin photolysis reactions, it appears unlikely that thymine dimer cleavage occurs via a direct energy transfer mechanism (160). One proposal suggests that in the model reaction with 1-deazariboflavin, the thymine dimer radical anion is formed via electron donation from the excited sensitizer (164). Alternatively, electron abstraction by the excited flavin could occur, resulting in the thymine dimer radical cation (159, 160), although it is unlikely that reduced flavin would act as an electron acceptor. A schematic for this mechanism is illustrated in Scheme 33, where the initial formation of a sensitizer-dimer complex is consistent with the observed saturation kinetics. The complex is activated by excitation of the ionized sensitizer (pH > 7), and electron donation to the dimer forms the dimer radical anion and the zwitterionic, neutral 1-deazariboflavin radical (162). Thymine dimer radical would spontane-... 

Fig. 6 Plot of the binding enthalpy for the flavin-DMF complex as a function of N(3)-0 distance in the oxidized and radical anion form, based on B3LYP calculations.

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