Reactivity of Dihydropterin Derivatives with H2O2 at Physiological pH

MARÍA L. DÁNTOLA; MARIANA VIGNONI; ALBERTO L. CAPPARELLI; CAROLINA LORENTE; ANDRÉS H. THOMAS

Los Cocos, Cordoba, Argentina

Congreso; CLAFQO-9 9na Conferencia Latinoamericana de Físico-química Orgánica; 2007

Hydrogen peroxide (H2O2) and pterin derivatives accumulate in the white skin patches of patients affected by vitiligo1. In this disease the protection of the skin against UV radiation fails due to the lack of melanin. Photochemical processes could play an important role in this disorder. Under UV-A radiation (320-400 nm) exposure, oxidized pterins are able to generate reactive oxygen species (ROS)2, very likely contributing to the oxidative stress and to the deactivation of enzymes of the melanin metabolism in the affected tissues. Pterin derivatives can exist in different oxidation states and they can be divided into two classes according to this property: a) oxidized or aromatic pterinas, containing the pyrazine[2,3-d]pyrimidine ring structure, and b) reduced pterins. Within the latter group, 7,8-dihydropterins and 5,6,7,8-tetrahydropterins are the most important derivatives due to their biological activity. Depending on their oxidation state, pterins present totally different reactivities towards oxidizing agents. Whereas oxidized pterins are quite stable in air, reduced pterins are able to react with molecular oxygen in its ground state. The stability of the reduced pterins in air-equilibrated solutions depends on the chemical structure of the pterin moiety as well as that of the substituent(s)3. Despite the biological and medical interest of the reactivity of dihydropterin derivatives with ROS, no systematic studies have been performed on the reactions between these compounds and  H2O2. In this work we evaluate the reactivity of a series of dihydropterins with H2O2. The study was performed in aqueous solution at physiological pH. We determined the rate constants of the reaction between H2O2 and dihydropterins, and investigated the corresponding oxidation products. The effect of the 6-substituent was analyzed. ([1]) Schallreuter, K. U.; Moore, J.; Wood, J. M.; Beazley, W. D.; Peters, E. M. J.; Marles, L. K.; Behrens-Williams, S. C.; Dummer, R.; Blau, N.; Thöny, B. J. Invest. Dermatol., 2001, 116, 167. (2) Lorente, C.; Thomas, A. H. Acc. Chem. Res., 2006, 39, 395. (3) Kirsch, M.; Korth, H.-G.; Stenert, V.; Sustmann, R.; De Groot, H. J. Biol. Chem., 2003, 278, 24481.