A DFT Study on the One-Electron Reduction/Oxidation of Biologically Relevant Pteridine Derivatives

Pteridine derivatives occur ubiquitously in living systems. The biological functions of these nitrogen-rich heterocyclic compounds remain partly unknown. The most intensively studied role is that of tetrahydrobiopterin as cofactor for the mono-oxygenases hydroxylating the aromatic amino acids phenylalanine, tyrosine and tryptophan. In these and other reactions pteridine derivatives act as redox catalysts; therefore, their redox behavior is of particular interest. Using density functional theory, one-electron reduction/oxidation processes involving relevant pteridine derivatives in aqueous solution are studied. For pterins and lumazines, the results reproduce very satisfactorily the experimentally known increasing reductive strength in the order aromatic, dihydro and tetrahydro compound. The influence of simple substituents at different molecular sites is studied. Results on quinoid dihydropterins not only confirm earlier experimental conclusions regarding the structure of these quite instable compounds, they also provide a theoretical rationale why quinoid dihydrobiopterin may have evolved as intermediate in the cofactor role of tetrahydrobiopterin.