The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Andrés H. Thomas - One of the best experts on this subject based on the ideXlab platform.
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alkane chain extended Pterin through a pendent carboxylic acid acts as triple functioning fluorophore 1o2 sensitizer and membrane binder
Photochemistry and Photobiology, 2019Co-Authors: Niluksha Walalawela, María Noel Urrutia, Andrés H. Thomas, Alexander Greer, Mariana VignoniAbstract:In order to develop a new long alkane chain Pterin that leaves the Pterin core largely unperturbed, we synthesized and photochemically characterized decyl Pterin-6-carboxyl ester (CapC) that preserves the Pterin amide group. CapC contains a decyl-chain at the carboxylic acid position and a condensed DMF molecule at the N2 position. Occupation of the long alkane chain on the pendent carboxylic acid group retains the acid-base equilibrium of the Pterin headgroup due to its somewhat remote location. This new CapC compound has relatively high fluorescence emission and singlet oxygen quantum yields attributed to the lack of through-bond interaction between the long alkane chain and the Pterin headgroup. The calculated lipophilicity is higher for CapC compared to parent Pterin and Pterin-6-carboxylic acid (Cap) and comparable to previously reported O- and N-decyl-Pterin derivatives. CapC's binding constant Kb (8000 M-1 in L-α-phosphatidylcholine from egg yolk) and ΦF :Φ∆ ratio (0.26:0.40) point to a unique triple function compound, although the hydrolytic stability of CapC is modest due to its ester conjugation. CapC is capable of the general triple action not only as a membrane intercalator, but also fluorophore and 1 O2 sensitizer, leading to a "self-monitoring" membrane fluorescent probe and a membrane photodamaging agent.
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photo oxidation of unilamellar vesicles by a lipophilic Pterin deciphering biomembrane photodamage
Langmuir, 2018Co-Authors: Mariana Vignoni, María Noel Urrutia, Alexander Greer, Helena Couto Junqueira, Ana Reis, Mauricio S Baptista, Rosangela Itri, Andrés H. ThomasAbstract:Pterins are natural products that can photosensitize the oxidation of DNA, proteins, and phospholipids. Recently, a new series of decyl-chain (i.e., lipophilic) Pterins were synthesized and their photophysical properties were investigated. These decyl-Pterins led to efficient intercalation in large unilamellar vesicles and produced, under UVA irradiation, singlet molecular oxygen, a highly oxidative species that react with polyunsaturated fatty acids (PUFAs) to form hydroperoxides. Here, we demonstrate that the association of 4-(decyloxy)pteridin-2-amine (O-decyl-Ptr) to lipid membranes is key to its ability to trigger phospholipid oxidation in unilamellar vesicles of phosphatidylcholine rich in PUFAs used as model biomembranes. Our results show that O-decyl-Ptr is at least 1 order of magnitude more efficient photosensitizer of lipids than Pterin (Ptr), the unsubstituted derivative of the Pterin family, which is more hydrophilic and freely passes across lipid membranes. Lipid peroxidation photosensitized ...
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Kinetic Control in the Regioselective Alkylation of Pterin Sensitizers: A Synthetic, Photochemical, and Theoretical Study
Photochemistry and Photobiology, 2018Co-Authors: Niluksha Walalawela, Mariana Vignoni, Sarah J. Belh, María Noel Urrutia, Andrés H. Thomas, Edyta M Greer, Alexander GreerAbstract:Alkylation patterns and excited-state properties of Pterins were examined both experimentally and theoretically. 2D NMR spectroscopy was used to characterize the Pterin derivatives, revealing undoubtedly that the decyl chains were coupled to either the O4 or N3 sites on the Pterin. At a temperature of 70°C, the Pterin alkylation regioselectively favored the O4 over the N3. The O4 was also favored when using solvents, in which the reactants had increased solubility, namely N,N-dimethylformamide and N,N-dimethylacetamide, rather than solvents in which the reactants had very low solubility (tetrahydrofuran and dichloromethane). Density functional theory (DFT) computed enthalpies correlate to regioselectivity being kinetically driven because the less stable O-isomer forms in higher yield than the more stable N-isomer. Once formed these compounds did not interconvert thermally or undergo a unimolecular "walk" rearrangement. Mechanistic rationale for the factors underlying the regioselective alkylation of Pterins is suggested, where kinetic rather than thermodynamic factors are key in the higher yield of the O-isomer. Computations also predicted greater solubility and reduced triplet state energetics thereby improving the properties of the alkylated Pterins as 1 O2 sensitizers. Insight on thermal and photostability of the alkylated Pterins is also provided.
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Effect of Pterin impurities on the fluorescence and photochemistry of commercial folic acid.
Journal of Photochemistry and Photobiology B-biology, 2018Co-Authors: M. Laura Dántola, M. Noel Urrutia, Andrés H. ThomasAbstract:Abstract Folic acid, or pteroyl‑ l ‑glutamic acid (PteGlu) is a conjugated Pterin derivative that is used in dietary supplementation as a source of folates, a group of compounds essential for a variety of physiological functions in humans. Photochemistry of PteGlu is important because folates are not synthesized by mammals, undergo photodegradation and their deficiency is related to many diseases. We have demonstrated that usual commercial PteGlu is unpurified with the unconjugated oxidized Pterins 6‑formylPterin (Fop) and 6‑carboxyPterin (Cap). These compounds are in such low amounts that a normal chromatographic control would not detect any Pterinic contamination. However, the fluorescence of PteGlu solutions is due to the emission of Fop and Cap and the contribution of the PteGlu emission, much lower, is negligible. This is because the fluorescence quantum yield (ΦF) of PteGlu is extremely weak compared to the ΦF of Fop and Cap. Likewise, the PteGlu photodegradation upon UV-A radiation is an oxidation photosensitized by oxidized unconjugated Pterins present in the solution, and not a process initiated by the direct absorption of photons by PteGlu. In brief, the fluorescence and photochemical properties of PteGlu solutions, prepared using commercially available solids, are due to their unconjugated Pterins impurities and not to PteGlu itself. This fact calls into question many reported studies on fluorescence and photooxidation of this compound.
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Lipophilic Decyl Chain–Pterin Conjugates with Sensitizer Properties
Molecular pharmaceutics, 2017Co-Authors: Mariana Vignoni, Niluksha Walalawela, Alexander Greer, Sergio M Bonesi, Andrés H. ThomasAbstract:A new series of decyl chain [-(CH2)9CH3] Pterin conjugates have been investigated by photochemical and photophysical methods, and with theoretical solubility calculations. To synthesize the Pterins, a nucleophilic substitution (SN2) reaction was used for the regioselective coupling of the alkyl chain to the O site over the N3 site. However, the O-alkylated Pterin converts to N3-alkylated Pterin under basic conditions, pointing to a kinetic product in the former and a thermodynamic product in the latter. Two additional adducts were also obtained from an N-amine condensation of DMF solvent molecule as byproducts. In comparison to the natural product Pterin, the alkyl chain Pterins possess reduced fluorescence quantum yields (ΦF) and increased singlet oxygen quantum yields (ΦΔ). It is shown that the DMF-condensed Pterins were more photostable compared to the N3- and O-alkylated Pterins bearing a free amine group. The alkyl chain Pterins efficiently intercalate in large unilamellar vesicles, which is a good indicator of their potential use as photosensitizers in biomembranes. Our study serves as a starting point where the synthesis can be expanded to produce a wider series of lipophilic, photooxidatively active Pterins.
Mariana Vignoni - One of the best experts on this subject based on the ideXlab platform.
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alkane chain extended Pterin through a pendent carboxylic acid acts as triple functioning fluorophore 1o2 sensitizer and membrane binder
Photochemistry and Photobiology, 2019Co-Authors: Niluksha Walalawela, María Noel Urrutia, Andrés H. Thomas, Alexander Greer, Mariana VignoniAbstract:In order to develop a new long alkane chain Pterin that leaves the Pterin core largely unperturbed, we synthesized and photochemically characterized decyl Pterin-6-carboxyl ester (CapC) that preserves the Pterin amide group. CapC contains a decyl-chain at the carboxylic acid position and a condensed DMF molecule at the N2 position. Occupation of the long alkane chain on the pendent carboxylic acid group retains the acid-base equilibrium of the Pterin headgroup due to its somewhat remote location. This new CapC compound has relatively high fluorescence emission and singlet oxygen quantum yields attributed to the lack of through-bond interaction between the long alkane chain and the Pterin headgroup. The calculated lipophilicity is higher for CapC compared to parent Pterin and Pterin-6-carboxylic acid (Cap) and comparable to previously reported O- and N-decyl-Pterin derivatives. CapC's binding constant Kb (8000 M-1 in L-α-phosphatidylcholine from egg yolk) and ΦF :Φ∆ ratio (0.26:0.40) point to a unique triple function compound, although the hydrolytic stability of CapC is modest due to its ester conjugation. CapC is capable of the general triple action not only as a membrane intercalator, but also fluorophore and 1 O2 sensitizer, leading to a "self-monitoring" membrane fluorescent probe and a membrane photodamaging agent.
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photo oxidation of unilamellar vesicles by a lipophilic Pterin deciphering biomembrane photodamage
Langmuir, 2018Co-Authors: Mariana Vignoni, María Noel Urrutia, Alexander Greer, Helena Couto Junqueira, Ana Reis, Mauricio S Baptista, Rosangela Itri, Andrés H. ThomasAbstract:Pterins are natural products that can photosensitize the oxidation of DNA, proteins, and phospholipids. Recently, a new series of decyl-chain (i.e., lipophilic) Pterins were synthesized and their photophysical properties were investigated. These decyl-Pterins led to efficient intercalation in large unilamellar vesicles and produced, under UVA irradiation, singlet molecular oxygen, a highly oxidative species that react with polyunsaturated fatty acids (PUFAs) to form hydroperoxides. Here, we demonstrate that the association of 4-(decyloxy)pteridin-2-amine (O-decyl-Ptr) to lipid membranes is key to its ability to trigger phospholipid oxidation in unilamellar vesicles of phosphatidylcholine rich in PUFAs used as model biomembranes. Our results show that O-decyl-Ptr is at least 1 order of magnitude more efficient photosensitizer of lipids than Pterin (Ptr), the unsubstituted derivative of the Pterin family, which is more hydrophilic and freely passes across lipid membranes. Lipid peroxidation photosensitized ...
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Kinetic Control in the Regioselective Alkylation of Pterin Sensitizers: A Synthetic, Photochemical, and Theoretical Study
Photochemistry and Photobiology, 2018Co-Authors: Niluksha Walalawela, Mariana Vignoni, Sarah J. Belh, María Noel Urrutia, Andrés H. Thomas, Edyta M Greer, Alexander GreerAbstract:Alkylation patterns and excited-state properties of Pterins were examined both experimentally and theoretically. 2D NMR spectroscopy was used to characterize the Pterin derivatives, revealing undoubtedly that the decyl chains were coupled to either the O4 or N3 sites on the Pterin. At a temperature of 70°C, the Pterin alkylation regioselectively favored the O4 over the N3. The O4 was also favored when using solvents, in which the reactants had increased solubility, namely N,N-dimethylformamide and N,N-dimethylacetamide, rather than solvents in which the reactants had very low solubility (tetrahydrofuran and dichloromethane). Density functional theory (DFT) computed enthalpies correlate to regioselectivity being kinetically driven because the less stable O-isomer forms in higher yield than the more stable N-isomer. Once formed these compounds did not interconvert thermally or undergo a unimolecular "walk" rearrangement. Mechanistic rationale for the factors underlying the regioselective alkylation of Pterins is suggested, where kinetic rather than thermodynamic factors are key in the higher yield of the O-isomer. Computations also predicted greater solubility and reduced triplet state energetics thereby improving the properties of the alkylated Pterins as 1 O2 sensitizers. Insight on thermal and photostability of the alkylated Pterins is also provided.
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lipophilic decyl chain Pterin conjugates with sensitizer properties
Molecular Pharmaceutics, 2017Co-Authors: Mariana Vignoni, Niluksha Walalawela, Alexander Greer, Sergio M Bonesi, Andrés H. ThomasAbstract:A new series of decyl chain [−(CH2)9CH3] Pterin conjugates have been investigated by photochemical and photophysical methods, and with theoretical solubility calculations. To synthesize the Pterins, a nucleophilic substitution (SN2) reaction was used for the regioselective coupling of the alkyl chain to the O site over the N3 site. However, the O-alkylated Pterin converts to N3-alkylated Pterin under basic conditions, pointing to a kinetic product in the former and a thermodynamic product in the latter. Two additional adducts were also obtained from an N-amine condensation of DMF solvent molecule as byproducts. In comparison to the natural product Pterin, the alkyl chain Pterins possess reduced fluorescence quantum yields (ΦF) and increased singlet oxygen quantum yields (ΦΔ). It is shown that the DMF-condensed Pterins were more photostable compared to the N3- and O-alkylated Pterins bearing a free amine group. The alkyl chain Pterins efficiently intercalate in large unilamellar vesicles, which is a good i...
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Lipophilic Decyl Chain–Pterin Conjugates with Sensitizer Properties
Molecular pharmaceutics, 2017Co-Authors: Mariana Vignoni, Niluksha Walalawela, Alexander Greer, Sergio M Bonesi, Andrés H. ThomasAbstract:A new series of decyl chain [-(CH2)9CH3] Pterin conjugates have been investigated by photochemical and photophysical methods, and with theoretical solubility calculations. To synthesize the Pterins, a nucleophilic substitution (SN2) reaction was used for the regioselective coupling of the alkyl chain to the O site over the N3 site. However, the O-alkylated Pterin converts to N3-alkylated Pterin under basic conditions, pointing to a kinetic product in the former and a thermodynamic product in the latter. Two additional adducts were also obtained from an N-amine condensation of DMF solvent molecule as byproducts. In comparison to the natural product Pterin, the alkyl chain Pterins possess reduced fluorescence quantum yields (ΦF) and increased singlet oxygen quantum yields (ΦΔ). It is shown that the DMF-condensed Pterins were more photostable compared to the N3- and O-alkylated Pterins bearing a free amine group. The alkyl chain Pterins efficiently intercalate in large unilamellar vesicles, which is a good indicator of their potential use as photosensitizers in biomembranes. Our study serves as a starting point where the synthesis can be expanded to produce a wider series of lipophilic, photooxidatively active Pterins.
Carolina Lorente - One of the best experts on this subject based on the ideXlab platform.
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Thymidine radical formation via one-electron transfer oxidation photoinduced by Pterin: Mechanism and products characterization.
Free Radical Biology and Medicine, 2016Co-Authors: Mariana P. Serrano, Mariana Vignoni, Patricia Vicendo, Esther Oliveros, Carolina Lorente, Andrés H. ThomasAbstract:Abstract UV-A radiation (320–400 nm), recognized as a class I carcinogen, induces damage to the DNA molecule and its components through different mechanisms. Pterin derivatives are involved in various biological functions, including enzymatic processes, and it has been demonstrated that oxidized Pterins may act as photosensitizers. In particular, they accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. We have investigated the ability of Pterin (Ptr), the parent compound of oxidized Pterins, to photosensitize the degradation of the pyrimidine nucleotide thymidine 5′-monophosphate (dTMP) in aqueous solutions under UV-A irradiation. Although thymine is less reactive than purine nucleobases, our results showed that Ptr is able to photoinduce the degradation of dTMP and that the process is initiated by an electron transfer from the nucleotide to the triplet excited state of Ptr. In the presence of molecular oxygen, the photochemical process leads to the oxidation of dTMP, whereas Ptr is not consumed. In the absence of oxygen, both compounds are consumed to yield a product in which the Pterin moiety is covalently linked to the thymine. This compound retains some of the spectroscopic properties of Ptr, such as absorbance in the UV-A region and fluorescence properties.
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Histidine oxidation photosensitized by Pterin: pH dependent mechanism.
Journal of Photochemistry and Photobiology B-biology, 2015Co-Authors: Carolina Castaño, Esther Oliveros, Andrés H. Thomas, Carolina LorenteAbstract:Abstract Aromatic Pterins accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder, due to the oxidation of tetrahydrobioPterin, the biologically active form of Pterins. In this work, we have investigated the ability of Pterin, the parent compound of aromatic Pterins, to photosensitize the oxidation of histidine in aqueous solutions under UV-A irradiation. Histidine is an α-amino acid with an imidazole functional group, and is frequently present at the active sites of enzymes. The results highlight the role of the pH in controlling the competition between energy and electron transfer mechanisms. It has been previously demonstrated that Pterins participate as sensitizers in photosensitized oxidations, both by type I (electron-transfer) and type II mechanisms (singlet oxygen (1O2)). By combining different analytical techniques, we could establish that a type I photooxidation was the prevailing mechanism at acidic pH, although a type II mechanism is also present, but it is more important in alkaline solutions.
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Degradation of α-melanocyte-stimulating hormone photosensitized by Pterin
Organic & biomolecular chemistry, 2014Co-Authors: Carolina Castaño, Esther Oliveros, Carolina Lorente, Nathalie Martins-froment, Andrés H. ThomasAbstract:Oxidized Pterins, efficient photosensitizers under UV-A irradiation, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. In this work, we have investigated the ability of Pterin (Ptr), the parent compound of oxidized Pterins, to photosensitize the oxidation of the peptide α-melanocyte-stimulating hormone (α-MSH), which stimulates the production and release of melanin by melanocytes in skin and hair. Our results showed that Ptr is able to photoinduce the degradation of α-MSH upon UV-A irradiation and that the reaction is initiated by an electron transfer from the peptide to the triplet excited state of Ptr. The photosensitized process produces chemical changes in at least two different amino acid residues: tryptophan and tyrosine (Tyr). It was shown that α-MSH undergoes dimerization and oxidation, the former process taking place after the formation of Tyr radicals. The present findings are analyzed in the context of the general behavior of Pterins as photosensitizers and the biological implications are discussed.
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Oxidation of Tyrosine Photoinduced by Pterin in Aqueous Solution
Photochemistry and Photobiology, 2013Co-Authors: Carolina Castaño, M. Laura Dántola, Esther Oliveros, Andrés H. Thomas, Carolina LorenteAbstract:Pterins, heterocyclic compounds widespread in biological systems, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. Pterins have been previously identified as good photosensitizers under UV-A irradiation. In this work, we have investigated the ability of Pterin (Ptr), the parent compound of oxidized Pterins, to photosensitize the oxidation of tyrosine (Tyr) in aqueous solutions. Tyr is an important target in the study of the photodynamic effects of UV-A radiation because it is oxidized by singlet oxygen (1O2) and plays a key role in polymerization and cross-linking of proteins. Steady UV-A irradiation of solutions containing Ptr and Tyr led to the consumption of Tyr and dissolved O2, whereas the Ptr concentration remained unchanged. Concomitantly, hydrogen peroxide (H2O2) was produced. By combining different analytical techniques, we could establish that the mechanism of the photosensitized process involves an electron transfer from Tyr to the triplet excited state of Ptr. Mass spectrometry, chromatography and fluorescence were used to analyze the photoproducts. In particular, oxygenated and dimeric compounds were identified.
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Tryptophan oxidation photosensitized by Pterin.
Free Radical Biology and Medicine, 2013Co-Authors: Andrés H. Thomas, Mariana P. Serrano, Patricia Vicendo, Virginie Rahal, Catherine Claparols, Esther Oliveros, Carolina LorenteAbstract:Abstract Pterins are normal components of cells and they have been previously identified as good photosensitizers under UV-A irradiation, inducing DNA damage and oxidation of nucleotides. In this work, we have investigated the ability of Pterin (Ptr), the parent compound of oxidized Pterins, to photosensitize the oxidation of another class of biomolecules, amino acids, using tryptophan (Trp) as a model compound. Irradiation of Ptr in the UV-A spectral range (350 nm) in aerated aqueous solutions containing Trp led to the consumption of the latter, whereas the Ptr concentration remained unchanged. Concomitantly, hydrogen peroxide (H 2 O 2 ) was produced. Although Ptr is a singlet oxygen ( 1 O 2 ) sensitizer, the degradation of Trp was inhibited in O 2 -saturated solutions, indicating that a 1 O 2 -mediated process (type II oxidation) was not an important pathway leading to Trp oxidation. By combining different analytical techniques, we could establish that a type I photooxidation was the prevailing mechanism, initiated by an electron transfer from the Trp molecule to the Ptr triplet excited state, yielding the corresponding radical ions (Trp + /Trp(-H) and Ptr − ). The Trp reaction products that could be identified by UPLC-mass spectrometry are in agreement with this conclusion.
Esther Oliveros - One of the best experts on this subject based on the ideXlab platform.
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Thymidine radical formation via one-electron transfer oxidation photoinduced by Pterin: Mechanism and products characterization.
Free Radical Biology and Medicine, 2016Co-Authors: Mariana P. Serrano, Mariana Vignoni, Patricia Vicendo, Esther Oliveros, Carolina Lorente, Andrés H. ThomasAbstract:Abstract UV-A radiation (320–400 nm), recognized as a class I carcinogen, induces damage to the DNA molecule and its components through different mechanisms. Pterin derivatives are involved in various biological functions, including enzymatic processes, and it has been demonstrated that oxidized Pterins may act as photosensitizers. In particular, they accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. We have investigated the ability of Pterin (Ptr), the parent compound of oxidized Pterins, to photosensitize the degradation of the pyrimidine nucleotide thymidine 5′-monophosphate (dTMP) in aqueous solutions under UV-A irradiation. Although thymine is less reactive than purine nucleobases, our results showed that Ptr is able to photoinduce the degradation of dTMP and that the process is initiated by an electron transfer from the nucleotide to the triplet excited state of Ptr. In the presence of molecular oxygen, the photochemical process leads to the oxidation of dTMP, whereas Ptr is not consumed. In the absence of oxygen, both compounds are consumed to yield a product in which the Pterin moiety is covalently linked to the thymine. This compound retains some of the spectroscopic properties of Ptr, such as absorbance in the UV-A region and fluorescence properties.
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Histidine oxidation photosensitized by Pterin: pH dependent mechanism.
Journal of Photochemistry and Photobiology B-biology, 2015Co-Authors: Carolina Castaño, Esther Oliveros, Andrés H. Thomas, Carolina LorenteAbstract:Abstract Aromatic Pterins accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder, due to the oxidation of tetrahydrobioPterin, the biologically active form of Pterins. In this work, we have investigated the ability of Pterin, the parent compound of aromatic Pterins, to photosensitize the oxidation of histidine in aqueous solutions under UV-A irradiation. Histidine is an α-amino acid with an imidazole functional group, and is frequently present at the active sites of enzymes. The results highlight the role of the pH in controlling the competition between energy and electron transfer mechanisms. It has been previously demonstrated that Pterins participate as sensitizers in photosensitized oxidations, both by type I (electron-transfer) and type II mechanisms (singlet oxygen (1O2)). By combining different analytical techniques, we could establish that a type I photooxidation was the prevailing mechanism at acidic pH, although a type II mechanism is also present, but it is more important in alkaline solutions.
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Degradation of α-melanocyte-stimulating hormone photosensitized by Pterin
Organic & biomolecular chemistry, 2014Co-Authors: Carolina Castaño, Esther Oliveros, Carolina Lorente, Nathalie Martins-froment, Andrés H. ThomasAbstract:Oxidized Pterins, efficient photosensitizers under UV-A irradiation, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. In this work, we have investigated the ability of Pterin (Ptr), the parent compound of oxidized Pterins, to photosensitize the oxidation of the peptide α-melanocyte-stimulating hormone (α-MSH), which stimulates the production and release of melanin by melanocytes in skin and hair. Our results showed that Ptr is able to photoinduce the degradation of α-MSH upon UV-A irradiation and that the reaction is initiated by an electron transfer from the peptide to the triplet excited state of Ptr. The photosensitized process produces chemical changes in at least two different amino acid residues: tryptophan and tyrosine (Tyr). It was shown that α-MSH undergoes dimerization and oxidation, the former process taking place after the formation of Tyr radicals. The present findings are analyzed in the context of the general behavior of Pterins as photosensitizers and the biological implications are discussed.
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Oxidation of Tyrosine Photoinduced by Pterin in Aqueous Solution
Photochemistry and Photobiology, 2013Co-Authors: Carolina Castaño, M. Laura Dántola, Esther Oliveros, Andrés H. Thomas, Carolina LorenteAbstract:Pterins, heterocyclic compounds widespread in biological systems, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. Pterins have been previously identified as good photosensitizers under UV-A irradiation. In this work, we have investigated the ability of Pterin (Ptr), the parent compound of oxidized Pterins, to photosensitize the oxidation of tyrosine (Tyr) in aqueous solutions. Tyr is an important target in the study of the photodynamic effects of UV-A radiation because it is oxidized by singlet oxygen (1O2) and plays a key role in polymerization and cross-linking of proteins. Steady UV-A irradiation of solutions containing Ptr and Tyr led to the consumption of Tyr and dissolved O2, whereas the Ptr concentration remained unchanged. Concomitantly, hydrogen peroxide (H2O2) was produced. By combining different analytical techniques, we could establish that the mechanism of the photosensitized process involves an electron transfer from Tyr to the triplet excited state of Ptr. Mass spectrometry, chromatography and fluorescence were used to analyze the photoproducts. In particular, oxygenated and dimeric compounds were identified.
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Tryptophan oxidation photosensitized by Pterin.
Free Radical Biology and Medicine, 2013Co-Authors: Andrés H. Thomas, Mariana P. Serrano, Patricia Vicendo, Virginie Rahal, Catherine Claparols, Esther Oliveros, Carolina LorenteAbstract:Abstract Pterins are normal components of cells and they have been previously identified as good photosensitizers under UV-A irradiation, inducing DNA damage and oxidation of nucleotides. In this work, we have investigated the ability of Pterin (Ptr), the parent compound of oxidized Pterins, to photosensitize the oxidation of another class of biomolecules, amino acids, using tryptophan (Trp) as a model compound. Irradiation of Ptr in the UV-A spectral range (350 nm) in aerated aqueous solutions containing Trp led to the consumption of the latter, whereas the Ptr concentration remained unchanged. Concomitantly, hydrogen peroxide (H 2 O 2 ) was produced. Although Ptr is a singlet oxygen ( 1 O 2 ) sensitizer, the degradation of Trp was inhibited in O 2 -saturated solutions, indicating that a 1 O 2 -mediated process (type II oxidation) was not an important pathway leading to Trp oxidation. By combining different analytical techniques, we could establish that a type I photooxidation was the prevailing mechanism, initiated by an electron transfer from the Trp molecule to the Ptr triplet excited state, yielding the corresponding radical ions (Trp + /Trp(-H) and Ptr − ). The Trp reaction products that could be identified by UPLC-mass spectrometry are in agreement with this conclusion.
M. Laura Dántola - One of the best experts on this subject based on the ideXlab platform.
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Effect of Pterin impurities on the fluorescence and photochemistry of commercial folic acid.
Journal of Photochemistry and Photobiology B-biology, 2018Co-Authors: M. Laura Dántola, M. Noel Urrutia, Andrés H. ThomasAbstract:Abstract Folic acid, or pteroyl‑ l ‑glutamic acid (PteGlu) is a conjugated Pterin derivative that is used in dietary supplementation as a source of folates, a group of compounds essential for a variety of physiological functions in humans. Photochemistry of PteGlu is important because folates are not synthesized by mammals, undergo photodegradation and their deficiency is related to many diseases. We have demonstrated that usual commercial PteGlu is unpurified with the unconjugated oxidized Pterins 6‑formylPterin (Fop) and 6‑carboxyPterin (Cap). These compounds are in such low amounts that a normal chromatographic control would not detect any Pterinic contamination. However, the fluorescence of PteGlu solutions is due to the emission of Fop and Cap and the contribution of the PteGlu emission, much lower, is negligible. This is because the fluorescence quantum yield (ΦF) of PteGlu is extremely weak compared to the ΦF of Fop and Cap. Likewise, the PteGlu photodegradation upon UV-A radiation is an oxidation photosensitized by oxidized unconjugated Pterins present in the solution, and not a process initiated by the direct absorption of photons by PteGlu. In brief, the fluorescence and photochemical properties of PteGlu solutions, prepared using commercially available solids, are due to their unconjugated Pterins impurities and not to PteGlu itself. This fact calls into question many reported studies on fluorescence and photooxidation of this compound.
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Oxidation of Tyrosine Photoinduced by Pterin in Aqueous Solution
Photochemistry and Photobiology, 2013Co-Authors: Carolina Castaño, M. Laura Dántola, Esther Oliveros, Andrés H. Thomas, Carolina LorenteAbstract:Pterins, heterocyclic compounds widespread in biological systems, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. Pterins have been previously identified as good photosensitizers under UV-A irradiation. In this work, we have investigated the ability of Pterin (Ptr), the parent compound of oxidized Pterins, to photosensitize the oxidation of tyrosine (Tyr) in aqueous solutions. Tyr is an important target in the study of the photodynamic effects of UV-A radiation because it is oxidized by singlet oxygen (1O2) and plays a key role in polymerization and cross-linking of proteins. Steady UV-A irradiation of solutions containing Ptr and Tyr led to the consumption of Tyr and dissolved O2, whereas the Ptr concentration remained unchanged. Concomitantly, hydrogen peroxide (H2O2) was produced. By combining different analytical techniques, we could establish that the mechanism of the photosensitized process involves an electron transfer from Tyr to the triplet excited state of Ptr. Mass spectrometry, chromatography and fluorescence were used to analyze the photoproducts. In particular, oxygenated and dimeric compounds were identified.
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Photosensitization of bovine serum albumin by Pterin: a mechanistic study.
Journal of photochemistry and photobiology. B Biology, 2013Co-Authors: Andrés H. Thomas, Carolina Lorente, Karina Roitman, Marisa Agüera Morales, M. Laura DántolaAbstract:Pterins, heterocyclic compounds widespread in biological systems, are able to photoinduce oxidation of DNA and its components. In the present study, we have investigated the photosensitizing properties of Pterin (Ptr), the parent compound of oxidized Pterins, using bovine serum albumin (BSA) as target. Aqueous solutions of BSA were exposed to UV-A irradiation (350nm) in the presence of Ptr, under various experimental conditions. The photosensitized processes were followed by UV/vis spectrophotometry, an enzymatic method for H2O2 determination and electrophoresis (SDS-PAGE). We present data that demonstrate unequivocally that BSA is damaged by Ptr. Although association between Ptr and the protein was evidenced by steady-state and time-resolved fluorescence measurements, the photosensitized damage takes place via a purely dynamic mechanism, which involves an electron transfer from BSA to the triplet excited state of Ptr, formed after UV-A excitation.
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Inactivation of tyrosinase photoinduced by Pterin
Biochemical and Biophysical Research Communications, 2012Co-Authors: M. Laura Dántola, Aldana D. Gojanovich, Andrés H. ThomasAbstract:Tyrosinase catalyzes in mammals the first and rate-limiting step in the biosynthesis of the melanin, the main pigment of the skin. Pterins, heterocyclic compounds able to photoinduce oxidation of DNA and its components, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder in which the protection against UV radiation fails due to the lack of melanin. Aqueous solutions of tyrosinase were exposed to UV-A irradiation (350 nm) in the presence of Pterin, the parent compound of oxidized Pterins, under different experimental conditions. The enzyme activity in the irradiated solutions was determined by spectrophotometry and HPLC. In this work, we present data that demonstrate unequivocally that the enzyme is photoinactivated by Pterin. The mechanism of the photosensitized process involves an electron transfer from tyrosinase to the triplet excited state of Pterin, formed after UV-A excitation of Pterin. The biological implications of the results are discussed.
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Production and quenching of reactive oxygen species by Pterin derivatives, an intriguing class of biomolecules
Pure and Applied Chemistry, 2010Co-Authors: Esther Oliveros, M. Laura Dántola, Mariana Vignoni, Andrés H. Thomas, Carolina LorenteAbstract:Pterins, a family of heterocyclic compounds derived from 2-aminopteridin-4(1H)- one, are widespread in living systems and participate in important biological functions, such as metabolic redox processes. Under UV-A excitation (320-400 nm), aromatic Pterins (Pt) can generate reactive oxygen species (ROS), as a consequence of both energy- and electron- transfer processes from their triplet excited state. Quantum yields of singlet oxygen ( 1 O 2 ) production depend largely on the nature of the substituents on the Pterin moiety and on the pH. Formation of the superoxide anion by electron transfer between the Pterin radical anion and molecular oxygen leads to the production of significant amounts of hydrogen peroxide (H 2 O 2 ) by disproportionation. DihydroPterins (H 2 Pt) do not produce 1 O 2 but are oxidized by this species with high rate constants yielding Pterins as well as H 2 O 2 . In contrast to aromatic derivatives, H 2 Pt are oxidized by H 2 O 2 , and rates and products strongly depend on the na- ture of the substituents on the H 2 Pt moiety. Aromatic Pterins have been found in vivo under pathological conditions, e.g., bioPterin or 6-carboxyPterin are present in the skin of patients affected by vitiligo, a depigmentation disorder. The biomedical implications of the produc- tion of ROS by Pterin derivatives and their reactivity with these species are discussed.
