Photochemistry of aromatic pterins
Six-substituted aromatic pterins undergo photooxidation in air-equilibrated aqueous solutions under UV-A radiation. Many of these oxidations chemically modify the six-subtituent but do not affect the pterin moiety or at least do so to a smaller extent. The mechanism involved in the photooxidation of these compounds strongly depends on the nature of the substituent at position 6 as well as on the pH (i.e., the photochemistry of the acid and basic forms of the pterin derivatives is different). In the following paragraphs, some examples of photochemistry of pterins relevant form a biomedical point of view are presented.
Neopterin (Nep) is synthesized mainly in activated macrophages and the concentration of this derivative in body fluids increases when the cellular immune system is activated. Biopterin (Bip), 6-formylpterin (Fop) and 6-carboxypterin (Cap) accumulate in the white skin patches of patients affected by vitiligo. Upon UV-A excitation, the singlet excited state of Bip or Nep undergoes intersystem crossing to yield the corresponding triplet excited state, which is converted into 6-formyl-5,8-dihydropterin (5,8-H2Fop), in an O2-independent process. This compound reacts very fast with O2 to yield Fop and O2•–, the latter being disproportionated to form H2O2. In the presence of O2, Fop is, in turn, photooxidized to Cap, which is much more photostable than Nep, Bip and Fop and then is accumulated in the solution.
Folic acid, or pteroyl-L-glutamic acid (PteGlu), is a precursor of coenzymes involved in the metabolism of nucleotides and amino acids. PteGlu is composed of three moieties: a 6-methylpterin (Mep) residue, a p-aminobenzoic acid (PABA) residue, and a glutamic acid (Glu) residue. Accumulated evidence indicates that photolysis of PteGlu leads to increased risk of several pathologies. When an air-equilibrated aqueous solution of PteGlu is exposed to UV-A radiation, the rate of the degradation increases with irradiation time. The mechanism involved in this “auto-photo-catalytic” effect was investigated in aqueous solutions using a variety of tools. Whereas PteGlu is photostable under anaerobic conditions, it is converted into Fop and p-aminobenzoyl-L-glutamic acid (PABA-Glu) in the presence of oxygen. As the reaction proceeds and enough Fop accumulates in the solution, a photosensitized electron-transfer process starts, where Fop photoinduces the oxidation of PteGlu to Fop, and H2O2 is formed. This process also takes place with other pterins as photosensitizers.
The photochemistry of the pterin moiety itself has been investigated using pterin and pterin derivatives containing substituents that cannot be easily oxidized, e.g., 6-carboxypterin and 6-methylpterin. The pterin moiety is photostable in these cases under anaerobic conditions, whereas excitation in the presence of O2 leads to oxidation, yielding nonpterinic photoproducts (cleavage of the pterin moiety) and H2O2. Although pterins are good 1O2 sensitizers and are able to quench 1O2, the chemical reaction between both species is not the only pathway of pterin moiety photooxidation. However, the quantum yields of disappearance of these compounds in the presence of oxygen are much lower than those corresponding to other derivatives bearing oxidizable substituents. Photochemistry of lumazine is similar to that of pterin.
"1H NMR characterization of the intermediate formed upon UV-A excitation of biopterin, neopterin and 6-hydroxymethylpterin in O2-free aqueous solutions" M. Vignoni, M. L. Salum, R. Erra-Balsells, A. H. Thomas, F. M. Cabrerizo, Chem. Phys. Lett., 484, 330, 2010. "Mechanism of photooxidation of folic acid sensitized by unconjugated pterins". M. L. Dántola, M. P. Denofrio, B. Zurbano, C. S. Gimenez, P. R. Ogilby, C. Lorente A. H. Thomas, Photochem. Photobiol. Sci., 9, 1604, 2010. "New results on the photochemistry of biopterin and neopterin" M. Vignoni, F. M. Cabrerizo, C. Lorente, A. H. Thomas, Photochem. Photobiol., 85, 365, 2009. "Photochemical and photophysical properties of lumazine in aqueous solutions" M. P. Denofrio, A. H. Thomas, A. M. Braun, E. Oliveros, C. Lorente, J. Photochem. Photobiol. A: Chem. 200, 282, 2008. "Photochemical behaviour of 6-methylpterin in Aqueous Solutions: Generation of Reactive Oxygen Species". F. M. Cabrerizo, C. Lorente, M. Vignoni, Romina Cabrerizo, A. H. Thomas, A. L. Capparelli. Photochem. Photobiol., 81, 793, 2005. "Photochemistry of Pterin in Acid and Alkaline Aqueous Solution". F. M. Cabrerizo, M. L. Dántola, A. H. Thomas, C. Lorente, A. M. Braun, E. Oliveros, A. L. Capparelli, Chem. Biodiv., 1, 1800, 2004. "Generation of reactive oxygen species during the photolysis of 6-hydroxymethylpterin in alkaline aqueous solutions" F. M. Cabrerizo, A. H. Thomas, C. Lorente, M. L. Dántola, G. Petroselli, Rosa Erra-Balsells, A. L. Capparelli, Helv. Chim. Acta, 87, 349, 2004. "Photochemical behavior of folic acid in alkaline aqueous solutions and evolution of its photoproducts" A. H. Thomas, G. Suárez, F. M. Cabrerizo, F. S. García Einschlag, R. Martino, C. Baiocchi, E. Pramauro, A. L. Capparelli, Helv. Chim. Acta, 85, 2300, 2002. "Photochemistry of 6-formylpterin in alkaline medium" A. H. Thomas, G. Suárez, F. M. Cabrerizo, A. L. Capparelli, Helv. Chim. Acta, 84, 3849, 2001. "Study of the photolysis of 6-carboxypterin in acid and alkaline aqueous solutions" G. Suárez, F. M. Cabrerizo, C. Lorente, A. H. Thomas, A. L. Capparelli, J. Photochem. Photobiol. A: Chem., 132, 53, 2000. "Study of the photolysis of folic acid and 6-formylpterin in acid aqueous solutions" A. H. Thomas, G. Suárez, F. M. Cabrerizo, R. Martino, A. L. Capparelli, J. Photochem. Photobiol. A: Chem., 135, 147, 2000.