Quinonoid dihydropterin

Naturally occurring pterin derivatives have existed in 3 oxidation states pterin (4 aromatic), dihydropterin (e.g., 5-8) and tetrahydropterin (9). In the present review, we do not refer to reduced pterin derivatives with reduced pyrimidine structures. The reduced pterin derivatives, dihydropterin and tetrahydropterin are readily oxidized to the corresponding aromatic form (4) under aerobic conditions. Based on the location to which hydrogen atoms are added, 4 kinds of dihydropterin have been defined 7,8-dihydropterin (5), quinonoid dihydropterin (6), 5,6-dihydropterin (7) and 5,8-dihydropterin (8). Of these, only 7,8-dihydropterin derivatives can be stored for long periods under non-aerobic conditions. Indeed, several 7,8-... 

Lunte, C.E. Kissinger, P.T. Study of the tautomerization of quinonoid dihydropterins by liquid chromatography/ electrochemistry. Anal. Chim. Acta 1984, 158, 33-41. 

The extension to 6MPH4 (19) of the observation of a PAH-catalyzed transient tetrahydropterin-derived intermediate that is a precursor of the quinonoid dihydropterin (22) has firmed the argument for the existence of a specific 4n-hydroxy adduct (21). The proof of structure rests on a striking similarity between its UV spectrum and that of the chemically synthesized 4a-hydroxy adduct derived from... 

In both chemical and enzymic (phenylalanine hydroxylase) oxidation of tetrahydropteridines.ortho-quinonoid dihydropterins... 

BH4 is essential for the AAHs to carry out their respective catalytic reactions and, at least for PAH, the prereductive activation, which appears to produce dihydrobiopterin quinonoid (g-BH2) directly (20). After the PAH catalytic cycle an oxygen atom is incorporated into the cofactor, providing 4a-OH-BH4 which dissociates from the active site. In order to regenerate the functional tetrahydro form of BH4 pterin carbinolamine dehydratase catalyzes the dehydration of 4-OH-BH4 to g-BH2, which is reduced back to by dihydropteridine reductase (Scheme 2). g-BH2 can also be converted to 7,8-dihydropterin (BH2) which can be regenerated to BH4 by dihydrofolate reductase (DHFR). 

The only reversible redox process observed under rapid scanning of potential in the entire scheme occurs between tetrahydropterin and the quinonoid tautomer of dihydropterin in step (a) [Scheme 2.3). All other redox processes in the scheme lead to unstable dihydropterin forms that rapidly rearrange to the most stable tautomer, 7,8-dihydro tautomer in step (b). While 7,8-dihy-dropterin can be oxidized to pterin in step (c), it is a much less favorable oxidation process requiring potentials -500 mV more positive than that for the reversible tetrahydro/quinonoid oxidation. Likewise 7,8-dihydropterin is reducible to tetrahydropterin but at potentials over 1 V more negative than reversible quinonoid/tetrahydro reduction. Such a low reduction potential accounts for unlikely participation of simple 7,8-H2pterins in any redox step of Moco catalysis. Reduction of fully oxidized pterin also generates an unstable 5,8-dihydropterin tautomer, which rearranges to the 7,8-dihydro tautomer step (d) before further reduction to tetrahydropterin can occur. 

The products 6, 7,10,12 and 13a-b (Schemes 2.4-2.7) were characterized by X-ray crystallography, which confirmed pterin chelation at the 04, N5-site and clearly showed saturation at atoms C6 and C7 as expected for a quinonoid isomer of dihydropterin. Each compound also showed a proton at N8. 

The second method of establishing oxidation states employed redox titration using the redox dye dichlorophenolindophenol (DCIP) based on the knowledge that tetrahydropterins reduce DCIP instantaneously while qui-nonoid dihydropterins react slowly and 7,8-dihydropterins do not reduce DCIP at all. As previously mentioned in this chapter, DCIP oxidation of Moeo within several molybdoenzymes was determined to be a two-electron process, suggesting a dihydropterin reduction state that was speculated to be the quinonoid tautomer. The results of stoichiometric additions of DCIP to the molybdenum complexes of reduced pterins showed that no oxidation of... 

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