Production and quenching of reactive oxygen species by pterin derivatives, an intriguing class of biomolecules

Abstract

Pterins, a family of heterocyclic compounds derived from 2-aminopteridin-4(1H)-one, are widespread in living systems and participate in important biological functions, such as metabolic redox processes. Under UV-A excitation (320-400 nm), aromatic pterins (Pt) can generate reactive oxygen species (ROS), as a consequence of both energy-and electron-transfer processes from their triplet excited state. Quantum yields of singlet oxygen (1O2) production depend largely on the nature of the substituents on the pterin moiety and on the pH. Formation of the superoxide anion by electron transfer between the pterin radical anion and molecular oxygen leads to the production of significant amounts of hydrogen peroxide (H2O2) by disproportionation. Dihydropterins (H2Pt) do not produce 1O2 but are oxidized by this species with high rate constants yielding pterins as well as H2O2. In contrast to aromatic derivatives, H2Pt are oxidized by H2O2, and rates and products strongly depend on the nature of the substituents on the H2Pt moiety. Aromatic pterins have been found in vivo under pathological conditions, e.g., biopterin or 6-carboxypterin are present in the skin of patients affected by vitiligo, a depigmentation disorder. The biomedical implications of the production of ROS by pterin derivatives and their reactivity with these species are discussed.