Degradation mechanism of nucleotides photosensitized by pterin

M.P. SERRANO; C. LORENTE; S. ESTEBANEZ; C. D. BORSARELLI; A.H. THOMAS

Santiago de Chile

Encuentro; 25th Inter-American Photochemical Society Meeting (25th I-APS Meeting); 2016

Universidad Católica de Chile

Pterins belong to a family of heterocyclic compounds present in a wide range of living systems and participate in relevant biological functions. Under UV-A excitation (320-400 nm), pterins can fluoresce, undergo photooxidation and generate reactive oxygen species (ROS) [1]. In the presence of oxygen, pterin (Ptr) act as photosensitizer through type I (electron transfer/H+ abstraction) and/or type II (1O2-singlet oxygen mediated oxidation) mechanisms [2-3]. The photosensitized degradations of purine and pyrimidine nucleotides (dNMP) by Ptr were studied in neutral aqueous solutions upon UV-A irradiation (350 nm) at room temperature, under different experimental conditions. The photochemical reactions were followed by UV-vis spectrophotometry and HPLC, and the photoproducts were analyzed by means of electrospray ionization mass spectrometry. Photophysical properties of the triplet excites states of the sensitizer were characterized using laser flash photolysis. After analysis of the results, reaction mechanisms were proposed. Under anaerobic conditions, for purine nucleotides, a recombination of the radicals occurred, and no consumption of the nucleotide was observed. On the other hand, for pyrimidine nucleotides, the formation of an adduct between the substrate and the sensitizer was observed. The fluorescence properties of the adduct are similar to those of Ptr itself. In the presence of O2, it was observed more consumption of the purine nucleotides than in O2-saturated solutions.In this case, there is a competition between different reactions that includes type I and type II mechanisms for guanine nucleotide. For the others nucleotides, which do not react with 1O2, the reaction is initiated by an electron transfer from the nucleotide to the triplet excited state of the pterin yielding the corresponding pair of radical ions (Pt?‾ and dNMP?+), with the subsequent recovery of the photosensitizer by electron transfer from Pt?‾ to O2. Finally, dNMP?+ participates in other reactions to yield degradation products.[1] Lorente, C.; et. al.; Acc. Chem. Res. 2006, 39, 395.[2] Petroselli, G.; et. al.; J. Am. Chem. Soc. 2008, 130, 3001.