The role of triplet states in the photooxidation of folic acid

M. PAULA DENOFRIO; M. LAURA DÁNTOLA; PETER R. OGILBY; CAROLINA LORENTE; ANDRÉS H. THOMAS

Mendoza

Conferencia; -American Photochemical Society, 21st I-APS Conference; 2011

Folic acid (PteGlu) and its derivatives (folates) are conjugated pterins widespread in biological systems. Their chemical structure is composed of three moieties: 6-methylpterin (Mep), p-aminobenzoic acid (PABA), and glutamic acid (Glu). Folate deficiency in pregnant women has clearly been shown to be related to neural tube defects.  It has been proposed that one of the main functions of skin pigmentation is to avoid photolysis of folates.  Due to the biological implications of the photodegradation of folates in humans, the photochemical behavior of PteGlu as a model compound becomes very interesting.In the absence of oxygen, PteGlu is photostable. However, excitation of PteGlu in air-equilibrated solutions leads to cleavage and oxidation of the molecule, yielding 6-formylpterin (Fop) and p-aminobenzoylglutamic acid (PABA-Glu) as photoproducts. ,  When an air-equilibrated aqueous solution of PteGlu is exposed to UV-A radiation, the rate of PteGlu degradation increases with irradiation time.3,4 Analysis of this “auto-photocatalytic” effect on the basis of the general photochemical behavior of pterins  suggests that the reaction consists in a photosensitized process in which the photoproduct (Fop) acts as a sensitizer of its own production. The first step would involve an electron transfer from the PABA ring of the substituent of PteGlu to the triplet excited state of the sensitizer.The aim of this work was to prove the interaction between the triplet state of unconjugated pterins and the substituent of PteGlu. With this in mind, quenching studies by means of laser flash photolysis were performed as previously described.  To avoid the excitation of the substrate and photolysis of the sensitizer, the experiments were carried out using Mep, a photostable unconjugated pterin, as sensitizer and PABA and PABA-Glu as quenchers. The results obtained in these flash photolysis experiments provide direct evidence for the reaction between the isolated substituent of PteGlu and the triplet state of Mep. Moreover, the values of the quenching rate constants obtained indicate a very efficient interaction. Most importantly, the data support the assumption that triplet states of oxidized pterins participate in the mechanism of the photosensitized oxidation of PteGlu