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Purine scaffolds constitute a starting point for the synthesis of numerous chemotherapeutics used in treating cancer, viruses, parasites, as well as bacterial and fungal infections. In this work, we synthesized a group of guanosine analogues containing an additional five-membered ring and a sulfur atom at the C-9 position. The spectral, photophysical, and biological properties of the synthesized compounds were investigated. The spectroscopic studies revealed that a combination of the thiocarbonyl chromophore and the tricyclic structure of guanine analogues shifts the absorption region above 350 nm, allowing for selective excitation when present in biological systems. Unfortunately, due to the low fluorescence quantum yield, this process cannot be used to monitor the presence of these compounds in cells. The synthesized compounds were evaluated for their effect on the viability of human cervical carcinoma (HeLa) and mouse fibroblast (NIH/3T3) cells. It was found that all of them display anticancer activity. In vitro studies were preceded by in silico ADME and PASS analyses, which confirmed that the designed compounds are promising candidates for anticancer agents.
Assuntos
Antineoplásicos , Animais , Camundongos , Humanos , Antineoplásicos/química , Células HeLa , Nucleosídeos de Purina , Guanosina , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
The mechanisms of one-electron protein oxidation are complicated and still not well-understood. In this work, we investigated the reaction of sensitized photo-oxidation using carboxybenzophenone (CB) as a sensitizer and a PR-10 protein (MtN13) as a quencher, which is intrinsically complicated due to the complex structure of the protein and multiple possibilities of CB attack. To predict and examine the possible reactions precisely, the 3D structure of the MtN13 protein was taken into account. Our crystallographic studies revealed a specific binding of the CB molecule in the protein's hydrophobic cavity, while mass spectrometry identified the amino acid residues (Met, Tyr, Asp and Phe) creating adducts with the sensitizer, thus indicating the sites of 3CB* quenching. In addition, protein aggregation was also observed. The detailed mechanisms of CB quenching by the MtN13 molecule were elucidated by an analysis of transient products by means of time-resolved spectroscopy. The investigation of the transient and stable products formed during the protein photo-oxidation was based on the data obtained from HPLC-MS analysis of model compounds, single amino acids and dipeptides. Our proposed mechanisms of sensitized protein photo-oxidation emphasize the role of a ground state complex between the protein and the sensitizer and indicate several new and specific products arising as a result of one-electron oxidation. Based on the analysis of the transient and stable products, we have demonstrated the influence of neighboring groups, especially in the case of Tyr oxidation, where the tyrosyl radical can be formed via a direct electron transfer from Tyr to CB* or via an intramolecular electron transfer from Tyr to Met radical cation Met > Sâ+ or thiyl radical CysSâ from neighboring oxidized groups.
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Aminoácidos , Cisteína , Oxirredução , Transporte de ElétronsRESUMO
Two graphene oxide nanoassemblies using 5-(4-(aminophenyl)-10,15,20-triphenylporphyrin (TPPNH2) were fabricated by two synthetic methods: covalent (GO-CONHTPP) and noncovalent bonding. GO-CONHTPP was achieved through amide formation at the periphery of GO sheets and the hybrid material was fully characterized by FTIR, XPS, Raman spectroscopy, and SEM. Spectroscopic measurements together with theoretical calculations demonstrated that assembling TPPNH2 on the GO surface in DMF-H2O (1:2, v/v) via non-covalent interactions causes changes in the absorption spectra of porphyrin, as well as efficient quenching of its emission. Interestingly, covalent binding to GO does not affect notably neither the porphyrin absorption nor its fluorescence. Theoretical calculations indicates that close proximity and π-π-stacking of the porphyrin molecule with the GO sheet is possible only for the non-covalent functionalization. Femtosecond pump-probe experiments revealed that only the non-covalent assembly of TPPNH2 and GO enhances the efficiency of the photoinduced electron transfer from porphyrin to GO. In contrast to the non-covalent hybrid, the covalent GO-CONHTPP material can generate singlet oxygen with quantum yields efficiency (ΦΔ = 0.20) comparable to that of free TPPNH2 (ΦΔ = 0.26), indicating the possible use of covalent hybrid materials in photodynamic/photothermal therapy. The spectroscopic studies combined with detailed quantum-chemical analysis provide invaluable information that can guide the fabrication of hybrid materials with desired properties for specific applications.
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The thio analogues of purine bases have been found to possess notable biological and pharmacological capabilities and have an important role to play as anticancer and immunosuppressive drugs. In this work a new tricyclic analogue of guanosine containing sulfur was synthesized, in particular, DTEG (2',3',5'-tri-O-acetyl-6,9-dithioethanoguanosine). Although there is promise for thiopurine derivatives for biomedical applications, there are some liabilities in regard to their exposure to light. As a preliminary survey for such difficulties with DTEG, this work looks into spectral and photophysical processes of DTEG using time-resolved and steady-state optical excitation. In contrast to other thiopurines, which have long-lived triplets, DTEG is shown to have a short-lived triplet making it less dangerous for singlet-oxygen sensitization. Even in anaerobic solutions, its photoreactivity is negligible. These various unusual photochemical properties of DTEG are consistent with DTEG being very promising as an alternative drug to the currently used 6-thiopurines. DTEG also has some interesting photophysical behavior that is distinct from other thioketones. Although thioketones have an unusual fluorescence violating Kasha's Rule and emitting from the second excited singlet state, DTEG does this also, but, in addition, it shows dual fluorescence by emitting from its first excited singlet as well. The assignments of the nature of these excited states are supported by DFT results. This theory and associated kinetic analysis show quantitatively that the dual fluorescence is, in part, tied to the relatively fast S2 to S1 internal conversion compared to other S2 decays and, in part, tied to the relatively slow nonradiative decay of S1 itself.
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Tionas , Fluorescência , CinéticaRESUMO
Hydroxyl radicals (HOâ¢) have long been regarded as a major source of cellular damage. The reaction of HO⢠with methionine residues (Met) in peptides and proteins is a complex multistep process. Although the reaction mechanism has been intensively studied, some essential parts remain unsolved. In the present study we examined the reaction of HO⢠generated by ionizing radiation in aqueous solutions under anoxic conditions with two compounds representing the simplest model peptide backbone CH3C(O)NHCHXC(O)NHCH3, where X = CH2CH2SCH3 or CH2SCH3, i.e., the Met derivative in comparison with the cysteine-methylated derivative. We performed the identification and quantification of transient species by pulse radiolysis and final products by LC-MS and high-resolution MS/MS after γ-radiolysis. The results allowed us to draw for each compound a mechanistic scheme. The fate of the initial one-electron oxidation at the sulfur atom depends on its distance from the peptide backbone and involves transient species of five-membered and/or six-membered ring formations with different heteroatoms present in the backbone as well as quite different rates of deprotonation in forming α-(alkylthio)alkyl radicals.
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Radical Hidroxila , Metionina , Cisteína , Radical Hidroxila/química , Metionina/química , Oxirredução , Peptídeos/química , Radiólise de Impulso , Sulfetos , Espectrometria de Massas em TandemRESUMO
Oxidation of methionine (Met) is an important reaction that plays a key role in protein modifications during oxidative stress and aging. The first steps of Met oxidation involve the creation of very reactive and short-lived transients. Application of complementary time-resolved radiation and photochemical techniques (pulse radiolysis and laser flash photolysis together with time-resolved CIDNP and ESR techniques) allowed comparing in detail the one-electron oxidation mechanisms initiated either by âOH radicals and other one-electron oxidants or the excited triplet state of the sensitizers e.g., 4-,3-carboxybenzophenones. The main purpose of this review is to present various factors that influence the character of the forming intermediates. They are divided into two parts: those inextricably related to the structures of molecules containing Met and those related to external factors. The former include (i) the protection of terminal amine and carboxyl groups, (ii) the location of Met in the peptide molecule, (iii) the character of neighboring amino acid other than Met, (iv) the character of the peptide chain (open vs cyclic), (v) the number of Met residues in peptide and protein, and (vi) the optical isomerism of Met residues. External factors include the type of the oxidant, pH, and concentration of Met-containing compounds in the reaction environment. Particular attention is given to the neighboring group participation, which is an essential parameter controlling one-electron oxidation of Met. Mechanistic aspects of oxidation processes by various one-electron oxidants in various structural and pH environments are summarized and discussed. The importance of these studies for understanding oxidation of Met in real biological systems is also addressed.
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Metionina/química , Peptídeos/química , Proteínas/química , Animais , Elétrons , Humanos , Metionina/análogos & derivados , Modelos Moleculares , Oxirredução , Processos Fotoquímicos , Radiólise de ImpulsoRESUMO
The conversion of ribonucleosides to 2'-deoxyribonucleosides is catalyzed by ribonucleoside reductase enzymes in nature. One of the key steps in this complex radical mechanism is the reduction of the 3'-ketodeoxynucleotide by a pair of cysteine residues, providing the electrons via a disulfide radical anion (RSSRâ¢-) in the active site of the enzyme. In the present study, the bioinspired conversion of ketones to corresponding alcohols was achieved by the intermediacy of disulfide radical anion of cysteine (CysSSCys)â¢- in water. High concentration of cysteine and pH 10.6 are necessary for high-yielding reactions. The photoinitiated radical chain reaction includes the one-electron reduction of carbonyl moiety by disulfide radical anion, protonation of the resulting ketyl radical anion by water, and H-atom abstraction from CysSH. The (CysSSCys)â¢- transient species generated by ionizing radiation in aqueous solutions allowed the measurement of kinetic data with ketones by pulse radiolysis. By measuring the rate of the decay of (CysSSCys)â¢- at λmax = 420 nm at various concentrations of ketones, we found the rate constants of three cyclic ketones to be in the range of 104-105 M-1s-1 at ~22 °C.
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Biomimética , Dissulfetos , Cetonas , Radical Hidroxila/química , Cinética , ÁguaRESUMO
The present study explored the correlation between the photocatalytic activity toward hydrogen production of the graphene-based materials and graphene oxide (GO) morphology. In this work we applied the technique based on the combination of time-dependent sonication and iterative centrifugation cascades, which were designed to achieve nanosheets size and the number of layers selection. First such obtained GO dispersions were characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM) and optical spectroscopy. Those combined measurements showed that the intensity of the π-π peak at 230 nm seems to be very sensitive to the number of layers of nanosheets. Next, GO dispersions were used to establish influence of the size and the number of layers of GO flakes on the photocatalytic hydrogen production in the photocatalytic system, containing eosin Y as a sensitizer, triethanolamine as a sacrificial electron donor, and CoSO4 as precatalyst. The H2 production efficiency varied by a factor of 3.7 for GO dispersions sonicated for various amount of time. Interestingly it was found that too long ultrasound treatment had negative impact on the GO enhancement of hydrogen production which was related to the fragmentation of GO flakes. The photocatalytic system produced the highest amount of H2 when graphene oxide occurs as monolayers and efficiency becomes lower with the decrease of GO sheets size. Our results demonstrate the importance of optimizing the size and the number of layers of the GO flakes prior to preparation of GO-based materials.
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Within the reactive oxygen species (ROS) generated by cellular metabolisms, hydroxyl radicals (HOâ¢) play an important role, being the most aggressive towards biomolecules. The reactions of HO⢠with methionine residues (Met) in peptides and proteins have been intensively studied, but some fundamental aspects remain unsolved. In the present study we examined the biomimetic model made of Ac-Met-OMe, as the simplest model peptide backbone, and of HO⢠generated by ionizing radiation in aqueous solutions under anoxic conditions. We performed the identification and quantification of transient species by pulse radiolysis and of final products by LC-MS and high-resolution MS/MS after γ-radiolysis. By parallel photochemical experiments, using 3-carboxybenzophenone (CB) triplet with the model peptide, we compared the outcomes in terms of short-lived intermediates and stable product identification. The result is a detailed mechanistic scheme of Met oxidation by HOâ¢, and by CB triplets allowed for assigning transient species to the pathways of products formation.
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Radical Hidroxila/química , Metionina/química , Peptídeos/química , Raios gama , Oxirredução , Fotólise , Radiólise de ImpulsoRESUMO
Graphene-based nanohybrids are good candidates for various applications. However, graphene exhibits some unwanted features such as low solubility in an aqueous solution or tendency to aggregate, limiting its potential applications. On the contrary, its derivatives, such as graphene oxide (GO) and reduced graphene oxide (RGO), have excellent properties and can be easily produced in large quantities. GO/RGO nanohybrids with porphyrins were shown to possess great potential in the field of photocatalytic hydrogen production, pollutant photodegradation, optical sensing, or drug delivery. Despite the rapid progress in experimental research on the porphyrin-graphene hybrids some fundamental questions about the structures and the interaction between components in these systems still remain open. In this work, we combine detailed experimental and theoretical studies to investigate the nature of the interaction between the GO/RGO and two metal-free porphyrins 5,10,15,20-tetrakis(4-aminophenyl) porphyrin (TAPP) and 5,10,15,20-tetrakis(4-hydroxyphenyl) porphyrin (TPPH)]. The two porphyrins form stable nanohybrids with GO/RGO support, although both porphyrins exhibited a slightly higher affinity to RGO. We validated finite, Lerf-Klinowski-type (Lerf et al. in J Phys Chem B 102:4477, 1998) structural models of GO ([Formula: see text]) and RGO ([Formula: see text]) and successfully used them in ab initio absorption spectra simulations to track back the origin of experimentally observed spectral features. We also investigated the nature of low-lying excited states with high-level wavefunction-based methods and shown that states' density becomes denser upon nanohybrid formation. The studied nanohybrids are non-emissive, and our study suggests that this is due to excited states that gain significant charge-transfer character. The presented efficient simulation protocol may ease the properties screening of new GO/RGO-nanohybrids.
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The reactions of protein oxidation play a significant role in many biological processes, especially in diseases development. Therefore, it is important to understand, how the protein molecule behaves in the presence of oxidants. In the present work, photo-oxidation of phytohormone-binding plant protein (VrPhBP) was investigated using light and 3-carboxybenzophenone (3CB) as a sensitizer (one electron oxidant). The protein interacts with the sensitizer in the ground state forming a weak binding complex leading to the presence of bound and free 3CB in solution. The early events and transient species (such as radicals and radical ions) formed during irradiation were characterised by transient spectroscopy showing the formation of the sulphur radical cation Met>Sâ+ (stabilized by (Sâ´N)+)and the tyrosyl radical TyrOâ on VrPhBP. Thus the 3CB excited triplet state was quenched by the Met and Tyr residues and mostly by Met (based on the deconvoluted transient absorption spectra).The presence of a Tyr side chain in the vicinity of a Met residue results in intramolecular electron transfer from Tyr to the Met>Sâ+ radical cation, leading to regeneration of the thioether side chain and formation of TyrOâ. The presence of other side chains close to Met, such as Arg or Lys can induce the stabilization of Met>Sâ+ via the formation of two-centered three-electron bonded species (Sâ´N)+. The transient species were additionally confirmed by stable product analysis. Based on SDS-PAGE, chromatography and mass spectrometry, the formation of methionine sulphoxide and Met-3CB adduct was identified together with di-Tyr cross links. On the basis of the experimental results the overall mechanism of VrPhBP photo-oxidation, from its early events to the formation of stable products, is described. In addition, a good correlation between the mechanisms of photooxidation of model compounds such as Met derivatives and peptides and those for real biological systems is emphasized.
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Proteínas de Plantas , Sulfetos , Proteínas de Transporte , Citocininas , Radicais Livres , OxirreduçãoRESUMO
Two noncovalent nanohybrids between cationic porphyrin (free-base TMPyP and zinc(II) ZnTMPyP) bearing cationic (N-methylpyridyl) groups and graphene oxide (GO) were constructed with the aim of generating a photocatalyst active for rhodamine B (RhB) degradation. The obtained materials were thoroughly characterized by steady-state and time-resolved absorption and emission methods, which indicated that metalation of the porphyrin with Zn(II) increases the affinity of the porphyrin toward the GO surface. Photocurrent experiment together with femtosecond transient absorption spectroscopy clearly showed the existence of electron transfer from the photoexcited porphyrin to GO. Both hybrid materials demonstrated higher photocatalytic activity toward RhB degradation as compared to GO; however, ZnTMPyP-GO exhibited more efficient performance (19% of RhB decomposition after 2 h of irradiation). Our data indicate that the presence of Zn(II) in the core of the porphyrin can promote charge separation in the ZnTMPyP-GO composites. The higher degradation rate seen with ZnTMPyP-GO as compared to the TMPyP-GO assemblies highlights the beneficial role of Zn(II)-metalation of the porphyrin ring.
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The kinetics of intramolecular-contact formation between remote functional groups in peptides with restricted conformational flexibility were examined using designed peptides with variable-length proline bridges. As probes for this motion, free radicals were produced using the â¢OH-induced oxidation at the C-terminal methionine residue of γ-Glu-(Pro)n-Met peptides (n = 0-3). The progress of the radicals' motion along the proline bridges was monitored as the radicals underwent reactions along the peptides' backbones. Of particular interest was the reaction between the sulfur atom located in the side chain of the oxidized Met residue and the unprotonated amino group of the glutamic acid moiety. Interactions between them were probed by the radiation-chemical yields (expressed as G values) of the formation of C-centered, α-aminoalkyl radicals (αN) on the Glu residue. These radicals were monitored directly or via their reaction with p-nitroacetophenone (PNAP) to generate the optically detected PNAPâ¢- radical anions. The yields of these αN radicals were found to be linearly dependent on the number of Pro residues. A constant decrease by 0.09 µM J-1 per spacing Pro residue of the radiation-chemical yields of G(αN) was observed. Previous reports support the conclusion that the αN radicals in these cases would have to result from (Sâ´N)+-bonded cyclic radical cations that arose as a result from direct contact between the ends of the peptides. Furthermore, by analogy with the rate constants for the formation of intramolecularly (Sâ´S)+-bonded radical cations in Met-(Pro)n-Met peptides ( J. Phys. Chem. B 2016, 120, 9732), the rate constants for the formation of intramolecularly (Sâ´N)+-bonded radical cations are activated to the same extent for all of the γ-Glu-(Pro)n-Met peptides. Thus, the continuous decrease of G(αN) with the number of Pro residues (from 0 to 3) suggests that the formation of a contact between the S-atom in the C-terminal Met residue and the N-atom of a deprotonated N-terminal amino group of Glu is controlled in peptides with 0 to 3 Pro residues by the relative diffusion of the Sâ¢+ and unoxidized N-atom. The overall rate constants of cyclization to form the (Sâ´N)-bonded radical cations were estimated to be 3.8 × 106, 1.8 × 106, and 8.1 × 105 s-1 for peptides with n = 0, 1, and 2 Pro residues, respectively. If activation is the same for all of the peptides, then these rate constants are a direct indication for the end-to-end dynamics along the chain.
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Ácido Glutâmico , Peptídeos , Descarboxilação , Oxirredução , ProlinaRESUMO
The mechanism of photooxidation of methionine (N-Ac-Met-NH-CH3, 1) and methyl-cysteine (N-Ac-MeCys-NH-CH3, 2) analogues by 3-carboxybenzophenone triplet (3CB*) in neutral aqueous solution was studied using techniques of nanosecond laser flash photolysis and steady-state photolysis. The short-lived transients derived from 3CB and sulfur-containing amino acids were identified, and their quantum yields and kinetics of formation and decay were determined. The stable photoproducts were analyzed using liquid chromatography coupled with high-resolution mass spectrometry. Substantial differences in the mechanisms were found for methionine and S-methyl-cysteine analogues for both primary and secondary photoreactions. A new secondary reaction channel (back hydrogen atom transfer from the ketyl radical to the carbon-centered α-thioalkyl radical yielding reactants in the ground states) was suggested. The detailed mechanisms of 3CB* sensitized photooxidation of 1 and 2 are proposed and discussed.
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The present study explores the influence of graphene oxide (GO) on deactivation pathways of the excited states of zinc 5,10,15,20-tetrakis(4-(hydroxyphenyl))porphyrin (ZnTPPH). The interaction of light with free ZnTPPH molecules and with ZnTPPH molecules adsorbed on graphene oxide sheets was probed via UV-vis spectroscopy, fluorescence spectroscopy, femtosecond pump-probe technique and nanosecond flash photolysis. Formation of the ground-state ZnTPPH-GO complex in solution was monitored by the red-shift of the porphyrin Soret absorption band. It was found that Stern-Volmer fluorescence quenching can be described in terms of two different quenching regimes depending on the GO concentration. In addition, our comprehensive analysis of the steady-state and time-resolved emission experiments led to the conclusion that the observed quenching was entirely attributable to a static mechanism. Laser flash photolysis showed that the triplet lifetime of the ZnTPPH increased in the presence of GO from 174 µs to 292 µs, which is related to the decrease in the rate constant of a radiationless decay mechanism involving rotation of the peripheral hydroxyphenyl rings of the porphyrin. Femtosecond transient absorption spectroscopy demonstrated the presence of a fast photoinduced electron transfer from the singlet excited state of ZnTPPH to the GO sheets, as indicated by the formation of a porphyrin radical cation. Quantum chemical calculations were used to gain deeper insights into the nature of the electronically excited states in the free ZnTPPH as well as in the ZnTPPH-GO complex.
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The solvent-composition dependence of quenching triplet states of benzophenone (3BP) by anisole in acetonitrile-water (ACN-H2O) mixtures was investigated by laser flash photolysis over the water mole fraction (xw) increasing from 0 to 0.92. Single exponential decay of 3BP was observed over the whole composition range. The quenching rate constant consistently increased with the water content but increased far more rapidly with xw > 0.7. The water-triggered electron-transfer (ET) mechanism was confirmed by a steeply growing quantum yield of the benzophenone ketyl radical anion, escaping back-ET when the partial water volume exceeded the acetonitrile one. The water-content influence on the 3BP quenching rate was described by a kinetic model accounting for the microheterogeneous structure of the ACN-H2O mixtures and the very different solubility of the reactants in the solvent components. According to the model, the ET mechanism occurs at a rate constant of 1.46 × 109 M-1 s-1 and is presumably assisted by the ACN-H2O hydrogen-bonding interaction.
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Tyrosine residues (Tyr) on proteins are a favoured site of one-electron oxidation due to their low one-electron reduction potentials. In this work, light-induced oxidation of Tyr residues was investigated using direct ionisation (via 266 nm light excitation) and sensitized photo-oxidation (by 3-carboxybenzophenone as sensitizer and 355 nm). Light emission (fluorescence) was observed at 410-440 nm as a result of Tyr oxidation. This novel light emission process is shown to be dependent on the solvent and aromatic ring substituents, however it does not depend on pH. It is proposed, that after initial formation of tyrosine phenoxyl radicals (TyrOâ) by one electron-oxidation, the TyrOâ absorbs a second photon to give an excited state species that undergoes subsequent light emission. The intensity of this emission depends on the Tyr concentration, and the detection of this emission can be used to identify and quantify one-electron formation of oxidized Tyr residues on proteins.
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Proteínas , Tirosina , Radicais Livres , Oxirredução , Tirosina/metabolismoRESUMO
Laser flash photolysis and high-resolution mass spectrometry were used to investigate the mechanism of one-electron oxidation of two S-alkylglutathiones using 3-carboxybenzophenone (3CB) as a photosensitizer. This report indicates an unexpected reaction pathway of the α-aminoalkyl radical cation (αN+) derived from the oxidation of S-alkylglutathiones. Instead of a common hydrolysis reaction of αN+ reported earlier for methionine and other sulfur-containing aminoacids and peptides, an intramolecular ring-closure reaction was found for S-alkylglutathiones.
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Elétrons , Glutationa/química , Alquilação , Lasers , Oxirredução , FotóliseRESUMO
In the course of studying silicon modifications to improve emission properties of commonly used organic compounds, biphenyl with dimethylsilylvinyl groups in the para position (3-Si) was investigated. A comparative study was performed on the exact C-analogue (3-C) and expanded to biphenyl and dimethylbiphenyl to emphasize the general trend observed. Compound 3-Si displayed emission properties clearly different than all of the investigated hydrocarbon compounds, i.e. twice stronger fluorescence (Φf = 0.6) and a 3-times larger radiative rate constant as compared to 3-C in acetonitrile. Searching for the source of the unique emission of 3-Si, singlet and triplet processes were investigated for all of the compounds using steady-state and time-resolved methods, and their principal photophysical parameters are reported. Experimental work was supported by the theoretical predictions obtained using the EOM-CCSD method. The results led to the conclusion that the strong emission of 3-Si must be due to silicon's presence that enhanced intensity borrowing from the strongly allowed S0 â S2 transition and the larger S1 â S0 transition moment.
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Thione-containing nucleobases have attracted the attention of the scientific community for their application in oncology, virology, and transplantology. The detailed understanding of the reactivity of the purine derivative 8-thioguanosine (8-TG) with reactive oxygen species (ROS) and free radicals is crucial for its biological relevance. An extensive investigation on the fate of 8-TG under both reductive and oxidative conditions is here reported, and it was tested by employing steady-state photooxidation, laser flash photolysis, as well as γ-radiolysis in aqueous solutions. The characterization of the 8-TG T1 excited state by laser flash photolysis and the photooxidation experiments confirmed that singlet oxygen is a crucial intermediate in the formation of the unexpected reduced product guanosine, without the formation of the usual oxygenated sulfinic or sulfonic acids. Furthermore, a thorough screening of different radiolytic conditions upon γ-radiation afforded the reduced product. These results were rationalized by performing control experiments in the predominant presence of each reactive species formed by radiolysis of water, and the mechanistic pathway scenario was postulated on these bases.