More than 50 years ago, it was discovered that 3,5,4′-trihydroxystilbene, known as resveratrol (RSV), was synthesized in plants under oxidative stress conditions, in particular as a consequence to high exposition to UVC or infections [1,2]. RSV is synthetized naturally as the trans-isomer, but its corresponding cis-isomer is also found in plants (Fig. 1).

Given the presence of RSV in edible vegetables and fruits, its consumption was related to beneficial antioxidant impact [3]. The accumulation of RSV was observed in grapevines leaves and berries but more interesting was the discovery that it is present in red wines and that it could provide protection to its regular consumers against atherogenesis due to its antioxidant action [4]. The observation in 1992 by Renaud and de Lorgeril that French population had a low incidence on coronary heart diseases, even though their diet was very rich in saturated lipids [5], made them think that RSV might be involved as protector, and elaborated the “French paradox”. This paradox proposed that moderate wine consumption, despites alcohol content, explained the low coronary heart disease risk. Moreover, one year later, Fitzpatrick et al. reported that red wines and grape juices cause a decrease in platelet aggregation and an increase in high-density lipoprotein cholesterol [6]. RSV levels were found to be considerably higher in red wines than in white wines, suggesting that red wine is better in cardiac disease prevention [7]. In recent years, the increase in the number of articles published on RSV has rapidly increased, due to the fact that numerous beneficial properties for human health are attributed to it, such as anti-inflammatory and anticancer activities, free-radical scavenging, and inhibition of lipid peroxidation antiviral among others [8]. RSV was classified as a phytoalexin, a family of chemically unrelated molecules involved in plants defense reaction during a variety of injuries, since it was evident that it is synthesized in response to stressful situations [9].

The oxidation of biomolecules is a normal event that occurs in all cells, but under normal physiological conditions it is kept under control. However, under conditions of high oxidative stress, such as exposure to solar radiation, the rate of oxidatively generated damage increases, and irreversible damage occurs. For this reason, the use of sunscreens and antioxidants is necessary to avoid and/or repair the damage. In literature there are frequent mentions about the antioxidant properties attributed to RSV, but little has been studied about the mechanism by which it protects biomolecules and cells from oxidative damage. In aqueous solutions exposed to UV radiation, trans-RSV undergoes degradation depending on the irradiation wavelength and the solvent [10]. In aqueous solution, and under UV-A radiation (365 nm), trans-RSV absorbs radiation and immediately undergoes isomerization, but the sum of the concentrations of both isomers (trans-RSV + cis-RSV) remains constant, indicating that isomerization is the main reaction [10]. However, in aqueous solution but under UV-B radiation (λ ≤ 300 nm), trans-RSV isomerizes to cis-RSV in a first step, and in a second step cis-RSV is degraded to oxidation products, given that both isomers absorbs radiation at these wavelength region [10].

Solar radiation participates in the oxidation of biomolecules, by both direct and indirect absorption of electromagnetic radiation. The UV component of the electromagnetic radiation that reaches the Earth's surface is almost exclusively UV-A (320-400 nm), representing more than 95 %, therefore, the direct damage caused by solar radiation to proteins, DNA and lipids is limited, but solar radiation does cause oxidative damage through indirect or photosensitized processes. Photosensitized oxidation involves a second molecule which absorbs the radiation, called photosensitizer (PS), and generates its corresponding singlet and triplet excited states (1PS* and 3PS*, respectively) [11]. Excited states are much more reactive than the corresponding ground state and can proceed through electron-transfer (type I mechanisms) or energy-transfer (type II mechanisms) reactions with suitable molecules. The initial step in type I photosensitized oxidations is an electron-transfer reaction or hydrogen abstraction between the PS in excited state and the biomolecule, to form a pair of radicals. In type II mechanisms, 3PS* reacts with molecular oxygen (O2) generating singlet oxygen (1O2) which is the oxidizing species [12]. Several compounds can be found in nature acting as photosensitizers, such as flavins, porphyrins, pterins, among others, being responsible of skin photocarcinogenesis and photoaging [13]. In particular, pterin (Ptr) absorb electromagnetic radiation in the UV-A region (Fig. 2a), efficiently generate singlet and triplet excited states (1Ptr* and 3Ptr*, respectively), and participate in photosensitized oxidations of various biomolecules, through a combination of type I and type II mechanisms, predominating type I at physiological pH (Scheme 1) [14]. Briefly, Ptr-photosensitized oxidation of a given biomolecule is initiated with an electron-transfer reaction between 3Ptr* and the biomolecule, where Ptr radical anion (Ptr•-) and a biomolecule radical cation (B•+) are formed, and B•+ undergoes subsequent oxidation reactions depending on the given biomolecule [14]. In aerated experimental conditions, Ptr is not consumed since it is recovered when Ptr•- reacts with O2, yielding superoxide anion which is disproportionate in hydrogen peroxide (H2O2) and O2 (Scheme 1).

In recent articles we have demonstrated that trans-RSV has the ability to prevent Ptr-photosensitized oxidation of 2′-deoxyguanosine 5′-monophosphate, tyrosine, and histidine [[15], [16], [17]]. The evidence indicates that the presence of trans-RSV do not avoid the formation of the corresponding biomolecule radicals (B•+/B(-H)•) but once they are formed, a second electron-transfer reaction occurs from trans-RSV to B•+/B(-H)• recovering the biomolecule. According to these observations, trans-RSV behaves like an electron donor. It was also observed after irradiation that trans-RSV isomerizes to cis-RSV [15].

It is known that under UV radiation, trans-stilbenes undergo isomerization to the corresponding cis-form by direct absorption (in the UV range) or in a photosensitized mechanism (both energy-transfer or electron-transfer mechanisms), depending on the experimental conditions [18,19]. It was reported that stilbene isomerization by direct absorption occurs via the singlet excited state, despite it is also possible from the much lower energy triplet excited state, which can be populated through energy transfer from a suitable photosensitizer. In this work, we report experimental and theoretical evidence of the interaction between Ptr excited states and both trans-RSV and cis-RSV, and on Ptr-photosensitized degradation of RSV. Systematic study of the kinetics and mechanisms involving trans-RSV when it is exposed to UV-A radiation (365 nm) in the presence of Ptr was performed, both in aerobic and anaerobic conditions. From experimental results, the mechanism involved could be initiated by energy-transfer and/or electron-transfer reactions. From the calculation of reaction energies with quantum chemistry techniques, we proposed the most feasible mechanism.