Photosensitized oxidation of 2´-deoxyguanosine 5´-monophosphate: mechanism of the competitive reactions and product characterization

MARIANA VIGNONI; SANDRA ESTÉBANEZ; ANDRÉS H. THOMAS; MARIANA PAULA SERRANO; CAROLINA LORENTE

Villa Carlos Paz , Córdoba, Argentina.

Congreso; XIII Encuentro Latinoamericano de Fotoquímica y Fotobiología (XIII ELAFOT); 2017

ELAFOT

UV-A radiation (320?400nm) induces modifications to different biomolecules through photosensitizedreactions[1]. Oxidized pterins are efficient photosensitizers that accumulatein the skin affected by vitiligo, and photoinduce the oxidation of guanine in aprocess initiated by an electron transfer from the nucleobase to the tripletexcited state of the photosensitizer[2]. In this work, we have investigated thedegradation of 2?-deoxyguanosine 5?-monophosphate (dGMP) photosensitized bypterin (Ptr), the parent compound of oxidized pterins, in aqueous solutionsunder UV-A irradiation. We identified five products containing the oxidizedguanine moiety: the deoxyribonucleoside 5?-monophosphate derivatives ofimidazolone (dIzMP), dehydroguanidinohydantoin (dDGhMP), guanidinohydantoin(dGhMP), oxazolone (dZMP) and spiroiminodihydantoin (dSpMP). Additionally aproduct denoted P680 according to its molecular weight was detected. P680consists of one molecule of dGMP linked to one molecule of dDGhMP. This productpresents an absorption band in UV-A region, and it can fluoresce with a maximumat 440 nm (Figure 1). The experimentalresults show that the degradation mechanism of dGMP is initiated by an electrontransfer from dGMP to the triplet excited state of Ptr (3Ptr*) yielding the correspondingpair of radicals: Ptr?− and dGMP?+. Reaction of the latter, in its deprotonatedform, with superoxide anion leads to dIzMP, which then yields dZMP.8-Oxo-7,8-dihydroguanosine 5?-monophophate (8-oxo-dGMP) is also formed fromdGMP?+ and then rapidly oxidizes to dDGhMP and dGhMP. The higher molecularweight product P680 is also formed from dGMP?+/dGMP(-H)? and its rate offormation increases when O2?? is eliminated. This fact indicates that in type Iphotooxidation of dGMP, new products not well characterized up to now, areformed upon elimination of O2??. This situation is very common in biologicalsystems due to the presence of quenchers of this reactive oxygen specie.Finally, dSpMP, the only product arising from the oxidation of dGMP by 1O2, isa minor product of the dGMP photosensitized degradation under our experimentalconditions. Figure 1.a)Spectroscopic features of P680. Absorption and emission spectrum of P680 (λexc = 330 nm). b) Proposed chemical structure of product P680. c) Schemeof dGMP photosensitized oxidation via type I (electron transfer) and type II(oxidation by 1O2) mechanisms. [1] Y. Matsumuraand H. N. Ananthaswamy, Toxicol. Appl. Pharmacol., 2004, 195, 298 [2] M. P. Serrano,C. Lorente, F. E. M. Vieyra, C. D. Borsarelli and A. H. Thomas, Phys. Chem. Chem. Phys., 2012,14, 11657.