Pterins, tetrahydro-, oxidation

The importance of the dihydro and tetrahydro oxidation states of pterins in biology has stimulated interest in the study of the chemical properties of these compounds, especially with respect to electron-transfer and radical reactions. It has become apparent, perhaps unsurprisingly, that the stability and reactivity of these oxidation states are very sensitive to substituent effects and the much greater stability of the fully conjugated pteridines is most evident. The oxidation of tetrahydropterins and the reduction of dihydropterins have become especially important in the chemistry of nitric oxide production in nature and in oxidative stress but the accumulation of relevant facts has not led so far to a detailed understanding of the chemical property relationships. Relevant information is summarized in the following section. 

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... 

Pterin, 6-methyl-5,6,7,8-tetrahydro-configuration, 3, 281 conformation, 3, 281 Pterin, 6-oximinomethyl-8-oxide... 

Pteridines are widely distributed in nature and function as pigments, biological markers, and cofactors of enzymatic reactions. The oxidized heteroaromatic forms show a characteristic fluorescence which allows easy detection even in low concentrations. However, the more active 5,6,7,8-tetrahydro derivatives are nonfluorescing and oxidizable and create experimental problems in handling this type of compound. So far, all naturally occurring pteridines have turned out to be derivatives of pterin (2) and lumazine (3) which are modified by different substituents and functional groups in the 6- and/or 7-position. 

Pterins are redox active in their own right and can adopt one of several oxidation levels, for example, fully oxidized, dihydro, or tetrahydro (Fig. 18). The stereochemical nature of MPT observed in each protein crystallographic study (13) is equivalent to that of the fully reduced, or tetrahydropterin, state. This argues against the existence of dihydropterin states such as 5,6-dihydrop-terin or 7,8-dihydropterin, and one of the various quininoid forms of the dihydropterin, in the crystalline forms of these enzymes that have been characterized by X-ray crystallography. However, it is important to note that, for the tricyclic structure of MPT, the tetrahydropterin state is equivalent to that of a dihydropterin, as manifest in the pyran ring-opened form of the bicyclic... 

The known redox roles of tetrahydropterins in biochemistry led Rajagopalan to investigate the redox behavior of the pterin unit of Moco. They titrated Moco within molybdoproteins (XO and SO) with two different oxidants, ferrocyanide and the redox dye dichlorophenol indophenol (DCIP), and obtained unexpected results two electron equivalents of either oxidant produced the spectral signature of a fully oxidized pterin (Scheme 2.1), a result only consistent with the pterin in Moco starting at the dihydro oxidation state rather than the tetrahydro state as initially proposed. The interpretation at the time was that the pterin in Moco, instead of the initially proposed tetrahydropterin structure, was a dihydropterin in an unusual tautomeric form. 

The fully oxidized state, the semi-redueed or dihydro state and the fully reduced or tetrahydro state (Seheme 2.2a-e) are the three main redox states of pterins interconverted by 2e , 2H reaetions. The complexity of pterin redox chemistry results from many tautomeric forms of the semi-redueed state (Scheme 2.2d-h), whieh, unless highly substituted, will eventually rearrange to the most thermodynamieally stable form, ca. the 7,8-dihydropterin (Scheme 2.2b)... 

---