Deazaflavin

The UV spectra have been used in studies of protonation and related covalent hydration, structural assignments and tautomerism (see appropriate Sections), as well as in studies of bridgehead addition to 5-deazapterins (79MI21500, 78TL2271) and related 5-deazaflavin derivatives (80JA1092). 

Oxidative substitutions at ring junction positions in various tetrahydro-5-deaza-pterins (79JA6068) and -flavins (77JA6721) have been studied, e.g. to give (13), and the oxidation-reduction reactions of 5-deazaflavins (e.g. 78CL1177, 80CPB3514) across the 1,5-positions, e.g. (19) (20), are involved in their co-enzymic role in enzymic oxidations (see Section... 

The 5-chloro in 5-deazaflavins is reactive (7SJHC181), but not the 8-chloro, in contrast to the flavin case (79LA1802), and 4-chloropyrimido[4,5-Z>]quinolinium salts are readily hydrolyzed (76JCS(Pl)l3l). 

Deazaflavin, 5-amino-synthesis, 3, 222 5-Deazaflavin, tetrahydro-oxidative substitutions, 3, 205 Deazaflavinium salts synthesis, 3, 228 5-Deazaflavinoids, 3-aryl-synthesis, 3, 219 Deazaflavins... 

Reactions of anilinouracils and CDI lead to 5-deazaflavins, as shown in the following scheme 11501... 

In analogy to this reaction, a substituted anilinouracil with CDI in trifluoroacetic acid was shown to yield the 5-deazaflavin with a trifluoromethyl group in the 5-position [151]... 

Scheme 2 Mechanism of repair of cyclobutane pyrimidine dimers (CPD) by a CPD photolyase. 8-HDF 8-hydroxy-5-deazaflavin, ET electron transfer. FADH reduced and de-protonated flavin-coenzyme...

Flavin Coenzymes.—5-Deazaflavin-adenine dinucleotide (2) can be prepared from the 5-deazaFMN,21 using a FAD pyrophosphorylase from rat liver.22 When the apoprotein of D-amino-acid oxidase from pig kidney is reconstituted with (2), no oxidation of D-alanine is observed, although the flavin chromophore in the reconstituted enzyme is reduced on the addition of DL-amino-acids.22 This has been interpreted as indicating that hydrogen transfer from the amino-acid to (2) can still... 

Alex, L. A., Reeve, J. N., Orme-Johnson, W. H. and Walsh, C. T. (1990) Cloning, sequence determination, and expression of the genes encoding the subunits of the nickel-containing 8-hydroxy-5-deazaflavin reducing hydrogenase from Methanobacterium thermoautotrophicum delta H. Biochemistry, 29, 7237-44. 

Michel, R., Massanz, C., Kostka, S., Richter, M. and Fiebig, K. (1995) Biochemical characterization of the 8-hydroxy-5-deazaflavin-reactive hydrogenase from Methanosarcina barkeri Fusaro. Eur. J. Biochem., 233, 727-35. 

Muth, E., Morschel, E. and Klein, A. (1987) Purification and characterization of an 8-hydroxy-5-deazaflavin- reducing hydrogenase from the archaebacterium Methanococcus voltae. Eur. J. Biochem., 169, 571-7. 

Selected entries from Methods in Enzymology [vol, page(s)] Determination of FMN and FAD by fluorescence titration with apoflavodoxin, 66, 217 purification of flavin-adenine dinucleotide and coenzyme A on p-acetoxymercurianiline-agarose, 66, 221 a convenient biosynthetic method for the preparation of radioactive flavin nucleotides using Clostridium kluyveri, 66, 227 isolation, chemical synthesis, and properties of roseoflavin, 66, 235 isolation, synthesis, and properties of 8-hydroxyflavins, 66, 241 structure, properties and determination of covalently bound flavins, 66, 253 a two-step chemical synthesis of lumiflavin, 66, 265 syntheses of 5-deazaflavins, 66, 267 preparation, characterization, and coenzymic properties of 5-carba-5-deaza and 1-... 

In Scheme 7, an aminouracil reacts with an o-halobenzaldehyde as 1,3-bis electrophile to provide a simple preparation of 5-deazaflavins (82CC1085). 

Methanogenic bacteria contain a series of unique coenzymes (Section F) among which is coenzyme F420, a 5-deazaflavin substituted by H at position 7 and - OH at position 8 (8-hydroxy-7,8-didemethyl-5-deazariboflavin).227 228... 

To avoid this problem, Brustlein and Bruice used a 5-deazaflavin to oxidize NADH nonenzymatically.237 When this reaction was carried out in 2HzO, no 2H entered the product at C-5, indicating that a hydrogen atom (circled in Eq. 15-24) had been transferred directly from NADH to the C-5 position. Similar direct transfer of hydrogen to C-5 of 5-deazariboflavin 5 -phosphate is catalyzed by flavoproteins such as N-methylglutamate synthase238 and acyl-CoA dehydrogenase.237 239... 

However, these experiments may not have established a mechanism for natural flavoprotein catalysis because the properties of 5-deazaflavins resemble those of NAD+ more than of flavins.239 Their oxidation-reduction potentials are low, they do not form stable free radicals, and their reduced forms don t react readily with 02. Nevertheless, for an acyl-CoA dehydrogenase the rate of reaction of the deazaflavin is almost as fast as that of natural FAD.238 For these enzymes a hydride ion transfer from the (3 CH (reaction type D of Table 15-1) is made easy by removal of the a-H of the acyl-CoA to form an enolate anion intermediate. 

To accomplish these reactions a surprising variety of specialized cofactors are needed.351 352 434 The first of these, coenzyme M, 2-mercaptoethane sulfonate, was discovered in 1974.436 It is the simplest known coenzyme. Later, the previously described 5-deazaflavin F420 (Section B), a nickel tetrapyrrole F430 (Chapter 16), methanopterin (Fig. 

Several selenoproteins have been found in certain bacteria and archaea. A hydrogenase from Methano-coccus vannielii contains selenocysteine.559 560 This enzyme transfers electrons from H2 to the C-5 si face of the 8-hydroxy-5-deazaflavin cofactor F q (Section B,4). The same bacterium synthesizes two formate dehydrogenases (see Fig 15-23), one of which contains Se. Two Se-containing formate dehydrogenases are made by E. coli. One of them, which is coupled to a hydrogenase in the formate hydrogen-lyase system (see Eq. 15-37), is a 715-residue protein containing selenocysteine at position 140.561-563 The second has selenocysteine at position 196 and functions with a nitrate reductase in anaerobic nitrate respiration.561... 

The three-pulse electron spin-echo envelope modulation (ESEEM) technique is particularly sensitive for detecting hyperfine couplings to nuclei with a weak nuclear moment, such as 14N. It has been used to probe the coordination state of nickel in two hydrogenases from M. tkermoautotrophicum, strain AH (56). One of these enzymes contains FAD and catalyzes the reduction of F420 (7,8-dimethyl-8-hydroxy-5-deazaflavin), while the other contains no FAD and has so far only been shown to reduce artificial redox agents such as methyl viologen. 

The catalytic effect of metal ions such as Mg2+ and Zn2+ on the reduction of carbonyl compounds has extensively been studied in connection with the involvement of metal ions in the oxidation-reduction reactions of nicotinamide coenzymes [144-149]. Acceleration effects of Mg2+ on hydride transfer from NADH model compounds to carbonyl compounds have been shown to be ascribed to the catalysis on the initial electron transfer process, which is the rate-determining step of the overall hydride transfer reactions [16,87,149]. The Mg2+ ion has also been shown to accelerate electron transfer from cis-dialkylcobalt(III) complexes to p-ben-zoquinone derivatives [150,151]. In this context, a remarkable catalytic effect of Mg2+ was also found on photoinduced electron transfer reactions from various electron donors to flavin analogs in 1984 [152], The Mg2+ (or Zn2+) ion forms complexes with a flavin analog la and 5-deazaflavins 2a-c with a 1 1 stoichiometry in dry MeCN at 298 K [153] ... 

---