Isoalloxazines

Isay reaction, 2, 79-80 3, 259 Ismelin 7, 656 Isoalloxazine oxidation states, 1, 252 Isoaminopterin synthesis, 3, 327 Isoarsindolines, 1, 543-544 Isoarsinoline, tetrahydro-synthesis, 1, 552-553 stability, 1, 552 Isoascorbic acid structure, 4, 552 ( )-IsoavenacioIide synthesis, 1, 416 Isoazapenem synthesis, 1, 465 Isobacteriochlorin synthesis, 4, 419 Isobacteriochlorin, dimethyl-biosynthesis, 1, 105 Isobacteriochlorin, methyl-biosynthesis, 1, 105 Isobacteriochlorin, trimethyl-biosynthesis, 1, 105 Isobarbituric acid Mannich reaction, 3, 71 synthesis, 3, 133... 

Oxidation of P-nicotinamide adenine dinucleotide (NADH) to NAD+ has attracted much interest from the viewpoint of its role in biosensors reactions. It has been reported that several quinone derivatives and polymerized redox dyes, such as phenoxazine and phenothiazine derivatives, possess catalytic activities for the oxidation of NADH and have been used for dehydrogenase biosensors development [1, 2]. Flavins (contain in chemical structure isoalloxazine ring) are the prosthetic groups responsible for NAD+/NADH conversion in the active sites of some dehydrogenase enzymes. Upon the electropolymerization of flavin derivatives, the effective catalysts of NAD+/NADH regeneration, which mimic the NADH-dehydrogenase activity, would be synthesized [3]. 

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. 

Alloxazines (295) have been considered to exist as such, and not as isoalloxazines (296, R = H), because their ultraviolet spectra and... 

Vitamin B2 or riboflavin is chemically defined as 7,8-dimethyl-10-(lY-D-tibityl)isoalloxazine. Figure 1 shows the oxidized and reduced form of the vitamin. The ending flavin (from the latin word flavus—yellow) refers to its yellowish color. 

Figure 11-2. Oxidoreduction of isoalloxazine ring in fiavin nucieotides via a semi-quinone (free radicai) intermediate (center).

Flavins — These are isoalloxazine derivatives methylated at Cg and C-j, with substituents at Ng The most important flavin, riboflavin, has a ribityl gronp (derived from ribitol) at Ng. 

Shinkai and Kunitake (1977b) prepared a hydrophobic flavin analogue, 3-hexadecyl-10-butylisoalloxazine [56]. Its absorption spectrum in CTAB micelles showed distinct shoulders at 420 nm and 460-470 nm, as in the flavin spectrum in organic solvents. This indicates that [56] is located in the hydrophobic region of the micelle. Isoalloxazine [56] bound to a cationic micelle readily oxidizes 2-mercaptoethanol, 1,4-butanedithiol, and thiophenol (Shinkai and Kunitake, 1977b Shinkai et al., 1977a). In non-micellar... 

Riboflavin is also known as vitamin B2. It contains a complex isoalloxazine ring that humans are unable to synthesize. The complex ring is hooked onto a live-carbon sugar derivative, ribitol, closely related to the ribose that occurs in RNA. The RDA for adult males is 1.3 mg/day and for adult females 1.1 mg/day. Values decrease with increasing age but increase in pregnancy and lactation. Organ meats, milk, bread products, and fortified cereals are substantial sources of riboflavin. 

Although this process is unusual, a similar one has been suggested for a 9-substituted isoalloxazine derivative where C=N photoreactivity is also involved. Distinction between the above reaction and abstraction through a disfavored five-membered transition state (but from a far more reactive -CHgOH) has also been made on the basis of deuterium isotope studies. 

Riboflavin contains an isoalloxazine ring linked to the reduced sugar ribitol. The sugar unit in riboflavin is the non-cyclic ribitol, so that FAD and FMN differ somewhat from the nucleotides we encounter in nucleic acids. 

This group includes the coenzyme forms of water-soluble vitamin B2 or riboflavin. Synthesis occurs by initial cyclohydrolase action on the guanine ring of GTP and subsequent steps lead to the synthesis of the isoalloxazine ring structure (see structures below). 

Riboflavin (vitamin Bj) is chemically specified as a 7,8-dimethyl-10-(T-D-ribityl) isoalloxazine (Eignre 19.22). It is a precnrsor of certain essential coenzymes, such as flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD) in these forms vitamin Bj is involved in redox reactions, such as hydroxylations, oxidative carboxylations, dioxygenations, and the reduction of oxygen to hydrogen peroxide. It is also involved in the biosynthesis of niacin-containing coenzymes from tryptophan. 

Flavin redox states in a dual flavin enzyme. (Left) Single-electron reduction of the isoalloxazine ring generates the semiquinone radical, while reduction by two electrons generates the fully reduced species. (Right) Five possible oxidation levels of a dual flavin enzyme, where the FMN reduction potential is held at a more positive value relative U) FAD. The flavins can theoretically accept a maximum of four electrons obtained from two NADPH. However, in NADPH-cytochrome P450, reductase, full reduction of the flavins is not normally reached when NADPH serves as the reductant. 

---