Oxidation of 2‘-Deoxyguanosine 5‘-Monophosphate Photoinduced by Pterin:  Type I versus Type II Mechanism

Abstract

UV-A radiation (320-400 nm) induces damage to the DNA molecule and its components through different photosensitized reactions. Among these processes, photosensitized oxidations may occur through electron transfer or hydrogen abstraction (type I) and/or the production of singlet molecular oxygen ((1)O2) (type II). Pterins, heterocyclic compounds widespread in biological systems, participate in relevant biological processes and are able to act as photosensitizers. We have investigated the photosensitized oxidation of 2'-deoxyguanosine 5'-monophosphate (dGMP) by pterin (PT) in aqueous solution under UV-A irrradiation. Kinetic analysis was employed to evaluate the participation of both types of mechanism under different pH conditions. The rate constant of (1)O2 total quenching (k(t)) by dGMP was determined by steady-state analysis of the (1)O2 NIR luminescence, whereas the rate constant of the chemical reaction between (1)O2 and dGMP (k(r)) was evaluated from kinetic analysis of concentration profiles obtained by HPLC. The results show that the oxidation of dGMP photosensitized by PT occurs through two competing mechanisms that contribute in different proportions depending on the pH. The dominant mechanism in alkaline media involves the reaction of dGMP with (1)O2 produced by energy transfer from the PT triplet state to molecular oxygen (type II). In contrast, under acidic pH conditions, where PT and the guanine moiety of dGMP are not ionized, the main pathway for dGMP oxidation involves an initial electron transfer between dGMP and the PT triplet state (type I mechanism). The biological implications of the results obtained are also discussed.

Photosensitization of peptides and proteins by pterin derivatives

“…More recently, the mechanism involved in the photosensitization of biomolecules by pterins were investigated in a series of studies carried out with free nucleotides [28][29][30] and amino acids [12][13][14]. It was shown that pterins can act as photosensitizers through both type I and type II mechanisms and that the predominant one depends on a combination of many factors, such as quantum yields of Taking into account the studies mentioned in the previous paragraph, a set of competitive mechanisms can be summarized to explain the photooxidation of different biomolecules (S) by pterin derivatives (Pt) (reactions [1][2][3][4][5][6][7][8][9][10][11][12] …”

Chemical changes in bovine serum albumin photoinduced by pterin

“…In the presence of oxygen, pterin (Ptr) [14], the parent and unsubstituted compound of oxidized pterins, acts as a photosensitizer through both type I (electron transfer or hydrogen abstraction) [15] and type II (production of 1 O 2 ) [16] mechanisms. Moreover, Ptr photoinduces DNA damage and the oxidation of purine nucleotides [17][18][19][20]. Therefore, taking into account the accumulation of pterins in the human skin under pathological conditions described in the previous paragraph, the photochemistry and, especially their photosensitizing properties of these compounds are of particular interest for the study of skin disease.…”

Theoretical Study on the Relative Energies of Neutral Pterin Tautomers

“…Under UV-A irradiation, the excited pterins may undergo photooxidation besides fluorescence emission. Pterins, chiefly 6-carboxy pterin, have been shown to photosensitize DNA damage by both type I (electron transfer) and type II (singlet oxygen) mechanisms (19)(20)(21)(22). Despite their important contribution, the electronic and geometrical features of related low-lying states as well as the explicit mechanism of photochemistry and photophysics of pterins are still unclear.…”