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

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

Ferrara

Congreso; XXIII IUPAC Symposium on Photochemistry; 2010

IUPAC

Pterins belong to a family of heterocyclic compounds derived from 2-aminopteridin-4(1H)-one. They participate in important biological functions [1], such as the synthesis of aminoacids and DNA nucleobases, the metabolism of nitric oxide or the activation of immune responses at the cellular level. Under UV-A irradiation (320–400 nm), these biomolecules can fluoresce, undergo photooxidation to produce different products and generate reactive oxygen species (ROS) such as singlet oxygen (1O2) [2]. Aromatic pterins (Pt) produce ROS, as a consequence of both energy and electron transfer processes from their triplet excited state. Quantum yields of 1O2 production depend largely on the nature of the substituents on the pterin moiety and on the pH [3]. Superoxide may be formed by electron transfer between the Pt radical anion and molecular oxygen leading to the production of significant amounts of H2O2 by disproportionation (M. L. Dántola et al., to be published). Pt have been found in vivo under pathological conditions, e.g. some Pt (biopterin, 6-carboxypterin) accumulate in the skin of patients affected by vitiligo, a depigmentation disorder [4]. The ROS sensitizing properties of Pt may be responsible for the observed phototoxic effects [5]. Reduced pterins (dihydro and tetrahydro derivatives) are  biologically active forms of pterin derivatives. They are present in the skin and act as co-factors of a variety of enzymes. Dihydropterins (H2Pt) do not produce 1O2 but are oxidized by this species with high rate constants yielding Pt, among other compounds [6a]. Moreover, very recent results have shown that H2Pt may undergo photodimerization and, in the presence of O2, may be photooxidized to the corresponding Pt with concomitant H2O2 release [6b]. As both Pt and H2Pt absorb in the UV-A spectral region and Pt act as photosensitizers of H2Pt oxidation, a phototoxic  autocatalytic process is started. Taking into account the important biomedical implications of the photochemistry of pterin derivatives results will be discussed in this context.   [1] Chemistry and Biology of Pteridines and Folates, J. E. Ayling, M. G. Nair and C. M. Baugh, Eds., Plenum Press, New York, 1993. [2] C. Lorente, A. H. Thomas, Acc. Chem. Res. 2006, 39, 395-402. [3] A. H. Thomas, C. Lorente, A. L. Capparelli, C. G. Martínez, A. M. Braun, E. Oliveros,  Photochem. Photobiol. Sci. 2003, 2, 245-250 (2003). [4] H. Rokos, W. D. Beazley, K. U. Schallreuter, Biochem. Biophys. Res. Commun. 2002, 292, 805-811. [5] G. Petroselli, M. L. Dántola, F. M. Cabrerizo, A. L. Capparelli, C. Lorente, E. Oliveros, A. H. Thomas, J. Am. Chem. Soc. 2008, 130, 3001-3011. [6] a) M. L. Dántola, A. H. Thomas, A. M. Braun, E. Oliveros, C. Lorente, J. Phys. Chem. A, 2007, 111, 4280-4288; b) M. Vignoni, F. M. Cabrerizo, C. Lorente, C. Claparols, E. Oliveros, A. H. Thomas, Org. Biomol. Chem. 2010, 8, 800-810.