Study of the photochemistry of folic acid in alkaline medium

ANDRÉS THOMAS; FRANCO CABRERIZO; GUSTAVO SUÁREZ; FERNANDO GARCÍA EINSCHLAG; RAÚL MARTINO; C. BAIOCCHI; EDMONDO PRAMAURO; ALBERTO CAPPARELLI

HELVETICA CHIMICA ACTA

Año: 2002 p. 2300 - 2315

0018-019X

The photolysis of folic acid (N-(4-{[(2-amino-1,4-dihydro-4-oxopteridin-6-yl)methyl]amino}benzoyl)-glutamic acid) in alkaline aqueous solution (pH 10.0 ± 11.0) was carried out at 350 nm at room temperature and monitored by UV/VIS spectrophotometry, anal. and prep. thin-layer chromatography (TLC), and highperformance liquid chromatography (HPLC, HPLC/MS). The folate species underwent at least two independent photo-oxidation pathways, which were not observed when the acid form was photolyzed at pH7. The presence of O2 was essential in these oxidation pathways. Evidence for the role of singlet oxygen was established. In one of the pathways, the folate underwent cleavage, yielding 6-formylpterin (2-amino-1,4-dihydro-4-oxopteridine-6-carboxaldehyde) and (4-aminobenzoyl)glutamic acid as photoproducts. The other pathway yielded a new photostable product A of molecular mass 455, which could be isolated and stored in acidic or neutral aqueous solution. However, A was rather unstable in alkaline media undergoing a thermal reaction to a product B of lower molecular mass (427). The kinetics of this thermal reaction was analyzed with a stopped-flow spectrophotometer. A linear dependence of the first-order rate constant with the OH concentration was observed. The corresponding bimolecular rate constant was 1.1 1 s1. The quantum yields of substrate consumption and of photoproduct formation were determined. The here-reported photochemical behavior of folate solutions departs from results in acid media, where phototransformation proceeded via the cleavage of the acid form into 6-formylpterin and (4-aminobenzoyl)glutamic acid as the first major photoproducts, and where no thermal reactions were observed.