Photochemical behavior of 6-formyl-7,8-dihydropterin at physiological pH

M. LAURA DÁNTOLA; CAROLINA LORENTE; ESTHER OLIVEROS; ANDRÉS H. THOMAS

Cubatao, San Paulo, Brasil

Congreso; IX Encuentro Latinoamericano de Fotoquímica y Fotobiología; 2008

CEPEMA-USP

            Pterins, heterocyclic compounds widespread in biological systems, are derived from 2-aminopteridin-4(1H)-one or pterin. The most common pterin derivatives are 6-substituted compounds. Pterins can exist in different oxidation states and be divided into two classes according to this property: (a) oxidized or aromatic pterins 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. In the skin of patients suffering vitiligo,[1] a common disorder that produces white patches of depigmentation, several reduced and oxidized pterins accumulate in the affected areas.[2] Hydrogen peroxide (H2O2), participates in the pathogenesis of this disease and is also accumulated in the depigmented epidermis.[2,3] Previously, we have demonstrated that dihydropterins present in biological systems are oxidize by oxidant species to 7,8-dihidroxanthopterin (H2Xap) and 6-formyl-7,8-dihydropterin (H2Fop).[4,5] Considering, that in the patches of patients suffering vitiligo the protection again UV radiation is deficient, the photochemistry of H2Fop and H2Xap under physiological conditions might be occur.             The aim of this work is to study the photolysis of the acid forms of H2Fop by visible light (438 nm) at physiological pH, in the presence and absence of oxygen. The photochemical reactions were followed by UV-visible spectrophotometry, high performance liquid chromatography (HPLC) and an enzymatic method for H2O2 determination. The quantum yields of substrate disappearance and of photoproducts formation were determined. In the presence and absence of oxygen, H2Fop is oxidize at the position C(7)-N(8) to yield 6-formylpterin. Nevertheless, under anaerobic conditions other photoproducts were detected. The quantum yields associated with the disappearance of H2Fop, determined in the presence and in the absence of O2, are similar (~1,0×10-2). In both conditions, about one molecule of H2O2 is generated for each molecule of H2Fop consumed. This results is very important from a biological point of view because in the skin of vitiligo´s patients, H2Fop is accumulated from the oxidation of 7,8-dihidrobiopterin. The photochemistry of this molecule generates H2O2 and an oxidized pterin which in the presence of UV-radiation generates more reactive oxygen species (1O2, H2O2). Therefore, the photooxidation of H2Fop might be an additional source of H2O2 in vitiligo.   [1] Kovacs, S.O. J. Am. Acad. Dermatol. 1998, 38, 647-666. [2] Schallreuter, K. U.; Wood, J. M.; Pittelkow, M. R.; Gutlich, M.; Lemke, K. R.; Rodl, W.; Swanson, N. N.; Hitzemann, K.; Ziegler, I. Science. 1994, 263, 1444-1446. [3] 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. J. Invest. Dermatol. 2001, 116, 167-174. [4] Dántola, M. L.; Vignoni, M.; Capparelli, A. L.; Lorente, C.; Thomas, A. H.  Helv. Chim. Acta. 2008, 91, 411-425. [5] Dántola, M. L.; Schuler, T. M.; Denofrio, M. P.; Vignoni, M.; Capparelli, A. L.; Lorente, C.; Thomas, A. H. Tetrahedron. 2008, 64, 8692-8699.