Flavin derivatives

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]. 

The electrodeposited film of flavin derivatives would be utilized as a functional material in combination with number dehydrogenases and pyridine coenzymes for the detection of great number of analytes. 

Tautomerism of type 197 198 has been postulated to occur in flavin derivatives on the basis of infrared spectral data. ... 

Examples of coenzymes vitamin-derived nucleotides for example adenosine phosphates ATP, ADP, AMP nicotinamide derivatives NAD+, NADH, NADP+, NADPH flavin derivatives FAD, FADH2 coenzyme A (abbreviated to CoA, CoASH or CoA-SH). 

Phosphoric acid molecules can form acid-anhydride bonds with each other. It is therefore possible for two nucleotides to be linked via the phosphate residues. This gives rise to dinucleotides with a phosphoric acid-anhydride structure. This group includes the coenzymes NAD(P) " and CoA, as well as the flavin derivative FAD (1 see p. 104). 

W. Wei, G. Zue, and E. S. Yeung, One-Step Concentration of Analytes Based on Dynamic Change in pH in Capillary Zone Electrophoresis, Anal. Chem. 2002, 74, 934 P. Britz-McKibbin, K. Otsuka, and S. Terabe, On-Line Focusing of Flavin Derivatives Using Dynamic pH Junction-Sweeping Capillary Electrophoresis with Laser-Induced Fluorescence Detection, Anal. Chem. 2002, 74, 3736. 

The reactivity of substituents attached to ring carbon atoms is of much interest, mainly when it concerns complex fused-ring thietanes linked to naturally occurring compounds. The representative example of such a case is conversion of the thymine-thietane derivative 55 to its flavin derivative 56 in the presence of 1-hydroxybenzotriazole (HOBT) and 2-(l -benzotriazole-l-yl)-l,l,3,3-tetramethyluronium tetrafluoroborate (TBTU) (Equation 12) <20050BC1937>. 

Alternatively to the DNA modifications in the previous two sections where the chromophore was attached to one of the four DNA bases, chromophores can be incorporated as artificial DNA bases substituting a natural base or even a whole base-pair. There is a large number of recently reported syntheses of chromophores as DNA base surrogates, e.g. flavine derivatives [26] and thiazole orange derivatives [42]. Additionally, a variety of phosphoramidites as DNA building blocks for the introduction of fluorophores into DNA are commercially available, e.g. acridine derivatives. Clearly, the synthetic protocols for this kind of DNA modification do not follow a principle strategy which can be applied in a versatile fashion, as is the case for the DNA base modifications mentioned in the previous sections. It is important to point out that in many cases it turned out to be useful to replace the 2 -deoxyribose moiety with acyclic linker systems. This was also the case during our attempts to synthesize ethidium-modified DNA, which will be described here briefly. 

Fig. 4.6.8. Chemical assay for investigation of reductive ET in DNA. T-T dimer (TAT) splitting is the chemical result of photoinduced ET from a distant flavin derivative as the charge donor D.

To give ourselves what we felt would be the best chance for success, most of our work to date has been concerned with the use of flavin derivatives as the enzyme modifying agents. There is already a great deal of information in the literature indicating that even model flavins can be quite effective catalysts (10). Since we could not be sure at the beginning of our research what would be the best enzyme template to... 

Various decomposition reactions of heterocyclic cations in aqueous solution are expected to proceed via pseudobase intermediates. These intermediates have been established for the alkaline decomposition of the pyridinium ring of nicotinamide adenine dinucleotide300 and for various solution transformations of flavin-derived cations.112,113,301-303 Nucleophilic substitution by hydroxide ion in various heteroaromatic cations almost certainly proceeds via the appropriate pseudobase tr-complexes.304,305... 

This chapter focuses on the progress and challenges in the field of photocatalysis as applied towards the water splitting reaction (Eq. 1.). More specifically, homogeneous molecule based systems that mimic the natural photosynthetic system are examined for their potential to drive reaction 1. A number of molecules, including porphyrins, metalloporphyrins and phthalocyanines,17 transition metal complexes of Ru, Os, Re, Rh, Pt, Cu,811 and acridine and flavin derivatives,1214 have been examined as the chormophores and sensitizers for light driven processes. 

The possibility that an electron-transfer path is involved in photo-sensitized oxygenation has been considered on several occasions. This is relevant in several fields of application, from the biomimetic oxygenation of indole and flavin derivatives [106] to pollutant control. With reference to latter, it has been suggested that SET occurs in heterogeneous photosensitized oxidation by solid semiconductors, in which the adsorbed substrate donates an electron to the photogenerated hole and... 

TLC on silica gel 60 plates was used in various TLC solvent systems for both determination and identification of flavin derivatives in baker s yeast and foods (plain yogurt and bioyogurt, raw egg white, and egg powder). 

Gliszczynska, A. Koziolowa, A. Chromatographic determination of flavin derivatives in baker s yeast. J. Chromatogr., A 1998, 822, 59-66. 

Gliszcznska, A. Koziolowa, A. Chromatographic identification of a new flavin derivative in plain yogurt. J. Agric. Food Chem. 1999, 47, 3197-3201. 

Figure 26 The manganese(lll) steroid porphyrin (28) embedded in a DPPC membrane acts as an oxidation catalyst and converts ethylbenzene into acetophenone. An e cascade mediated by the amphiphilic flavin derivative (30) (F in the picture) reduces manganese(III) porphyrin to manganese(II) porphyrin which activates and transfers molecular oxygen [92] (FAD denotes tightly bound flavin adenine dinucleotide cofactor)...

Some enzymes require participation of coenzymes or metal ions for catalytic activity. Flavin derivatives (20) can be considered as an example of coenzyme analogues attached to artificial enzymes. The reactivity of flavin derivatives attached to a PEI derivative or a cationic polystyrene derivative was considerably greater than that of monomeric flavin analogues. ... 

Chemical reduction of activated flavin by DTT or NADH as donors of protons, apparently does not result in the modifications of the structure of the flavin derivate molecule. When using a chemically reduced substrate we have found that the affinity of the aldehyde for luciferase differed insignificantly from the native form. Thus it is... 

A variety of pyrimidine dimer-cleaving photochemical model systems have been developed to aid in the study and elucidation of the DNA-PL reaction mechanism (752, 158, 159). Direct excitation of pyrimidine dimers does not occur on ultraviolet or visible irradiation, suggesting that enzyme cofactors might be involved in a photosensitization process 146). Model systems utilizing free flavin derivatives have recently been described 137, 160). Rokita and Walsh have demonstrated that lumiflavin, 5-deazariboflavin, and 8-methoxy-7,8-didemethyl-7V °-ethyl-5-deazaflavin (Scheme 31) are effective photosensitizers for the thymine dimer cleavage reaction 160). These reactions utilized cis-syn-thymine dimer as substrate with irradiation at the Xmax of the flavin derivative, under strict anaerobic conditions and high pH. Flavin derivatives that contain electron-rich substituents at the 8-position, such as 8-hydroxy-5-deazariboflavin,... 

Flavin-dependent oxynitrilase has many properties common to flavoprotein oxidases. The enzyme binds sulfite in an N5 adduct, and one-electron reduction produces anionic semiquinone.The sulfite adduct and one- or two-electron reduced enzyme are inactive, as is apoenzyme, suggesting that the flavin is involved in catalysis. When the flavin is replaced by 5-carba-5-deaza FAD, a low level of activity is retained. " " However, when the enzyme containing the artificial flavin is exposed to H2O2, the isoalloxazine ring system is partially degraded to a redox-inactive heterocyclic system. " After the formation of this redox-inactive flavin derivative, enzyme activity actually increases dramatically, suggesting that the flavin plays a structural role. It is possible that the redox state of the flavin serves a regulatory role, since enzyme activity decreases when the natural flavin is reduced however, this has yet to be proven. 

O. Tillberg L. Torbjornsson, X-Ray Structure Investigation of Flavin Derivatives. In Elavins and Elavoproteins] H. Kamin, Ed. University Park Press Baltimore, 1971 pp 1-22. 

---