Flavin adenine dinucleotide , aromatic

Direct hydroxylation of an aromatic ring to yield a hydroxybenzene (a phenol) is difficult and rarely done in the laboratory., but occurs much more frequently in biological pathways. An example is the hydroxylation of p-hydroxyphenyl acetate to give 3,4-dihydroxyphenyl acetate. The reaction is catalyzed by p-hydroxyphenylacctate-3-hydroxylase and requires molecular oxygen plus the coenzyme reduced flavin adenine dinucleotide, abbreviated FADH2. 

Most coenzymes have aromatic heterocycles as major constituents. While enzymes possess purely protein structures, coenzymes incorporate non-amino acid moieties, most of them aromatic nitrogen het-erocycles. Coenzymes are essential for the redox biochemical transformations, e.g., nicotinamide adenine dinucleotide (NAD, 13) and flavin adenine dinucleotide (FAD, 14) (Scheme 5). Both are hydrogen transporters through their tautomeric forms that allow hydrogen uptake at the termini of the quinon-oid chain. Thiamine pyrophosphate (15) is a coenzyme that assists the decarboxylation of pyruvic acid, a very important biologic reaction (Scheme 6). 

A model of a flavin-based redox enzyme was prepared.[15] Redox enzymes are often flavoproteins containing flavin cofactors flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN). They mediate one- or two-electron redox processes at potentials which vary in a range of more than 500 mV. The redox properties of the flavin part must be therefore tuned by the apoenzyme to ensure the specific function of the enzyme. Influence by hydrogen bonding, aromatic stacking, dipole interactions and steric effects have been so far observed in biological systems, but coordination to metal site has never been found before. Nevertheless, the importance of such interactions for functions and structure of other biological molecules make this a conceivable scenario. 

Tissue also contains some endogenous species that exhibit fluorescence, such as aromatic amino acids present in proteins (phenylalanine, tyrosine, and tryptophan), pyridine nucleotide enzyme cofactors (e.g., oxidized nicotinamide adenine dinucleotide, NADH pyridoxal phosphate flavin adenine dinucleotide, FAD), and cross-links between the collagen and the elastin in extracellular matrix.100 These typically possess excitation maxima in the ultraviolet, short natural lifetimes, and low quantum yields (see Table 10.1 for examples), but their characteristics strongly depend on whether they are bound to proteins. Excitation of these molecules would elicit background emission that would contaminate the emission due to implanted sensors, resulting in baseline offsets or even major spectral shifts in extreme cases therefore, it is necessary to carefully select fluorophores for implants. It is also noteworthy that the lifetimes are fairly short, such that use of longer lifetime emitters in sensors would allow lifetime-resolved measurements to extract sensor emission from overriding tissue fluorescence. 

Figure 38. A, Circular dichroism spectra of -nicotinamide-adenine dinucleotide ( -NAD) as a function of temperature showing the reciprocity between the adenine band just below 260 nm and the nicotinamide band near 270 nm. These reciprocal relations in optical rotation qualitatively demonstrate a close interaction of the two aromatic rings. Reproduced, with permission, from [98]. B, Circular dichroism curves of flavin-adenine dinucleotide (FAD) as a function of water/dioxane mixtures. As the solvent becomes more polar, there is increased proximity of the two aromatic rings, as shown by the reciprocal changes in the intensity of the adenine band below 260 nm and the isoalloxazine band of flavin near 270 nm. Reproduced, with permission, from [99].

Other molecules that can accept two electrons are flavins FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide). The former coenzyme is formed by adenine-ribose-diphosphate, followed by a linear sugar-type molecule and, finally, the aromatic ring (isoalloxazine) of Figure 11.7. FMN is missing adenine, ribose, and one of the phosphates at the beginning of the chain. Flavins are prosthetic groups in fiavoproteins involved in the ET chain of Complex 11. 

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