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Chryssostomos Chatgilialoglu

Publications and source records attributed to Chryssostomos Chatgilialoglu.

At least 19 recordsLinked to original sources
PubMed2007

Reactions of hydrogen atoms with met-enkephalin and related peptides.

The reactions of hydrogen atoms with enkephalins and related peptides have been investigated by radiolytic methods in aqueous solutions and lipid vesicle suspensions. Pulse radiolysis experiments indicate that methionine residue (Met) is the main target. In Met-enkephalin (Tyr-Gly-Gly-Phe-Met) the attack of the hydrogen atom occurs to about 50 % on Met with formation of methanethiyl radical. The remaining percentage is divided roughly evenly between Tyr and Phe. With Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) the site of attack is limited to Tyr and Phe. Using a peptide-liposome (that is, 1-palmitoyl-2-oleoyl phosphatidylcholine vesicles) model, the cis-trans isomerization of phospholipids could be detected due to the catalytic action of thiyl radicals. The radiation chemical yields of the H(.) and, consequently of CH(3)S(.) radical, was modulated by the experimental conditions and the nature of peptide. Large amounts of trans lipids observed in phosphate buffer vesicle suspensions indicated the efficient role of double-bond isomerization as marker of Met-containing peptide damage.

Enkephalin, Leucine↗
PubMed2006

Tautomerism in the guanyl radical.

Despite a few decades of intense study, a full description of tautomers of one-electron-oxidized guanine remains to be achieved. Here we show that two of these tautomers are produced by the protonation of an 8-haloguanine electron adduct. The rate constants for the reactions of hydrated electrons (e(aq)(-)) with a variety of 8-substituted guanine derivatives have been measured by a pulse radiolysis technique and correlated with both inductive and resonance components of the substituents. The fate of electron adducts was investigated by radiolytic methods coupled with product studies and addressed computationally by means of time-dependent DFT (TD-B3LYP/6-311G**//B1B95/6-31+G**) calculations. The reaction of e(aq)(-) with 8-haloguanosine or 8-halo-2'-deoxyguanosine produces the first observable transient species that decay unimolecularly (k = 1 x 10(5) s(-)(1) at 22 degrees C) to give the one-electron oxidized guanosine or 2'-deoxyguanosine. Theory suggests that the electron adducts of 8-bromoguanine derivatives protonated at C8 form a pi-complex, with the Br atom situated above the molecular plane, that is prompt to eject Br(-). The two short-lived intermediates, which show a substantial difference in their absorption spectra, are recognized to be the two purine tautomers (i.e., iminic 7 and aminic 3 forms). The spin density distributions of the two tautomers are quite different at the O6 and N10 positions, whereas they are very similar at the N3, C5, and C8 positions. The resonance structures of the two tautomers are discussed in some detail. B1B95/6-31+G calculations show also that the tautomerization from the iminic (7) to the aminic (3) arrangement is a water-assisted process.

Journal Article↗
PubMed2006

Chemical radiation studies of 8-bromo-2'-deoxyinosine and 8-bromoinosine in aqueous solutions.

The reactions of hydrated electrons (e(aq) (-)) with 8-bromo-2'-deoxyinosine (8) and 8-bromoinosine (12) have been investigated by radiolytic methods coupled with product studies and have been addressed computationally by means of BB1K-HMDFT calculations. Pulse radiolysis revealed that one-electron reductive cleavage of the C--Br bond gives the C8 radical 9 or 13 followed by a fast radical translocation to the sugar moiety. Selective generation of a C5' radical occurs in the 2'-deoxyribo derivative, whereas in the ribo analogue the reaction is partitioned between the C5' and C2' positions with similar rates. Both C5' radicals undergo cyclizations, 10-->11 and 14-->15, with rate constants of 1.4 x 10(5) and of 1.3 x 10(4) s(-1), respectively. The redox properties of radicals 10 and 11 have also been investigated. A synthetically useful photoreaction has also been developed as a one-pot procedure that allows the conversion of 8 to 5',8-cyclo-2'-deoxyinosine in a high yield and a diastereoisomeric ratio (5'R)/(5'S) of 4:1. The present results are compared with data previously obtained for 8-bromoadenine and 8-bromoguanine nucleosides. Theory suggests that the behavior of 8-bromopurine derivatives with respect to solvated electrons can be attributed to differences in the energy gap between the pi*- and sigma*-radical anions.

Journal Article↗
PubMed2006

Trans-fatty acids and radical stress: what are the real culprits?

Free radical-catalysed cis-trans isomerization of unsaturated lipids in biomimetic models and their significance in eukaryotic cells have been explored in the last few years, an integrating hypothesis being that trans-fatty acids have their origins in both dietary sources and from isomerization of natural isomers by an endogenous radical stress. In this perspective, a summary of the achievements and a discussion of the possible biological sources of isomerizing radical species are given, indicating a need for further research on thiyl radical generation in biological systems. In this context, crucial questions remain to be answered by free radical research involving membrane lipids, thus contributing to lipidomics and embracing biology and medicine.

Fatty Acids↗
PubMed2006

C5'-adenosinyl radical cyclization. A stereochemical investigation.

A variety of substituted 2'-deoxyadenosin-5'-yl radicals 3 were generated under different reaction conditions. Radicals 3 underwent intramolecular cyclization onto the C8-N7 double bond of the adenine moiety leading to aminyl radicals (5'S,8R)-4 and (5'R,8R)-4 and, eventually, to the corresponding cyclonucleosides 5 and 6. The effect of the solvent, the nature of the substituents, and the generation method of radicals 3 on the stereoselectivity of the C5'-radical cyclization have been considered. The observed increase of the (5'S)/(5'R) ratio by increasing the bulkiness of the R1 group is explained in terms of steric repulsion between R1 and the purine moiety which favors the C5'-endo conformation, whereas the effect of the water solvent in promoting the (5'R)-stereoselective cyclization is ascribed to intermolecular hydrogen bonding stabilizing the C5'-exo conformation.

Cyclization↗
PubMed2006

Occurrence of trans fatty acids in rats fed a trans-free diet: a free radical-mediated formation?

Trans isomers of unsaturated fatty acids are absorbed from the diet, due to their presence in diary fat and hydrogenated vegetable oils, and health concern has risen due to their effects on lipid risk factors in cardiovascular diseases. On the basis of the efficiency of the thiyl-radical-catalyzed cis/trans isomerization in vitro and the presence of many sulfur-containing compounds in the cell, the aim of this study was to demonstrate that trans geometry of lipid double bonds can be endogenously generated within membrane phospholipids. The study reports trans fatty acids occurrence in tissue and erythrocyte phospholipids of young adult rats fed a diet completely free of trans isomers. Results show that tissues are differently prone to the endogenous isomerization and that, following a free radical attack, trans fatty acids can reach very high amounts. The effectiveness of this process is considerably inhibited in the presence of all-trans retinol, confirming previous data in model membranes. Our results suggest that geometrical isomerization of unsaturated fatty acids, which causes a structural modification of membrane lipids and may influence basic membrane properties and vital biochemical functions, can occur under radical stress conditions and could be efficiently prevented by vitamin A.

Animals↗
PubMed2006

The reaction of hydrogen atoms with methionine residues: A model of reductive radical stress causing tandem protein-lipid damage.

The occurrence of tandem damage, due to reductive radical stress involving proteins and lipids, is shown by using a biomimetic model. It is made of unsaturated lipid vesicle suspensions in phosphate buffer in the presence of methionine, either as a single amino acid or as part of a protein such as RNase A, which contains four methionine residues. The radical process starts with the formation of H(.) atoms by reaction of solvated electrons with dihydrogen phosphate anions, which selectively attack the thioether function of methionine. The modification of methionine to alpha-aminobutyric acid is accompanied by the formation of thiyl radicals, which in turn cause the isomerization of the cis fatty acid residues to the trans isomers. The relationship between methionine modification and lipid damage and some details of the reductive radical stress obtained by proteomic analysis of irradiated RNase A are presented.

Biomimetics↗
PubMed2005

The influence of solid-state molecular organization on the reaction paths of thiyl radicals.

Electron paramagnetic resonance (EPR) spectroscopy has been employed to investigate the effect of solid-state molecular organization on the reaction of thiyl radicals with thiols. In an irradiated C18H37SH/thiourea clathrate, the conversion of thiyl to perthiyl radicals is substantial, due to the head-to-head arrangement of the reactants within the channels and the suppression of other possible competing reactions due to hindrance by the clathrate walls. The perthiyl radical was identified using EPR analysis of its molecular dynamics within the clathrate channels. Irradiated polyethylene film containing 30% C18H37SH afforded a negligible conversion of thiyl to perthiyl radicals because of the random distribution of reactants. These results suggest that in the absence of favorable structure-control effects, the reaction between RS* and RSH is unimportant with respect to other competing reactions. Perthiyl radicals are also the major product in the vacuum solid-state radiolysis of lysozyme. A proposal of the mechanism involved in all cases is based on the equilibrium RS* + RSH <==> RSS*(H)R, followed by the irreversible conversion of the sulfuranyl radical to the perthiyl radical. As the equilibrium is strongly shifted to the left, the intermediate sulfuranyl radicals were not detected, but the lack of other competing reactions for the thiyl radicals caused the formation of perthiyl radicals to become the major path in the clathrate and in solid lysozyme radiolysis.

Electron Spin Resonance Spectroscopy↗
PubMed2005

Synthesis of all-trans arachidonic acid and its effect on rabbit platelet aggregation.

A simple and high-yielding method to convert natural all-cis PUFA derivatives to the corresponding all-trans geometrical isomers is described. The method is based on the thiyl radical-catalyzed cis-trans isomerization. The all-trans isomer of arachidonic acid was found to cause rabbit platelet aggregation at concentrations higher than 0.1 mM and inhibition of PAF-induced platelet aggregation in a concentration dependent manner with an IC(50) in the micromolar range.

Animals↗
PubMed2005

Trans lipid formation induced by thiols in human monocytic leukemia cells.

Trans lipids in humans originate exogenously from the ingestion of isomerized fats. An endogenous path comprising a thiyl radical-catalyzed cis-trans isomerization of cis-unsaturated phospholipids was proposed. However, whether an isomerization process might be feasible in eukaryotic cells remained to be established. Here we report the presence of trans lipids in human monocytic leukemia cell membranes (THP-1) before and after treatment with a 10 mM series of thiols. Oleic, linoleic, and arachidonic acid residues of membrane phospholipids were analyzed and, unexpectedly, an initial trans lipid content was found in control cells. Then, incubation for 24 h with thiols under physiological conditions slightly increased trans lipid content. Formation of trans isomers was also evaluated in the presence of thiol and under free radical stress induced by gamma-irradiation or by thermal decomposition of azo-compounds. The similarity of isomer trends formed under incubation and stress conditions, together with the reactivity order of fatty acid residues (arachidonic > linoleic approximately oleic), indicated a common radical path and some mechanistic considerations are advanced. These results offer the first evidence that trans lipids are formed in eukaryotic cells and confirm that thiyl radicals are harmful to the integrity of cis lipid geometry. This work motivates further studies into the relationship between lipid isomerization outcome and thiyl radicals in cellular systems, as well as the formation of trans lipids and the metabolic response to such a perturbation introduced into biological membranes.

Cell Differentiation↗
PubMed2005

Geometrical trans lipid isomers: a new target for lipidomics.

Evidence that lipids play different roles in the biological environment, particularly in dealing with metabolic regulation and cell signaling, has led to a growing interest in these molecules, and nowadays the research field of lipid structures and functions is called lipidomics. The term describes diverse research areas, from mapping the entire spectrum of lipids in organisms to describing the function and metabolism of individual lipids. Recent investigations on geometrical trans isomers of fatty acid derivatives, which have the double bonds in the same position as the natural compounds but with the trans instead of the naturally occurring cis geometry, highlighted these compounds as a new target for lipidomics. In addition to the identification of their structures and functions, research in a multidisciplinary context aims at understanding the biochemical significance of cis and trans lipid geometry, and a chemical biology approach can be envisaged to explore the role of the geometry change as either an alteration or a signal that can perturb a biological system and induce a cellular response.

Animals↗
PubMed2005

The kinetics of Z/E isomerization of methyl oleate catalyzed by photogenerated thiyl radicals.

The reaction of beta-mercaptoethanol with methyl oleate in tertbutyl alcohol was investigated under photochemical conditions. The time-dependent Z/E isomerization of the unsaturated moiety as well as the thiol-adduct formation were analyzed on the basis of radical generation rates and established rate constants. This provides precise room-temperature rate constants for the reversible thiyl radical addition to both Z and E isomers. The rate constants for HOCH2CH2S* addition to the Z and E forms were found to be 1.6 x 10(5) and 2.9 x 10(5) M(-1) S(-1), respectively. For the beta-elimination of the thiyl radical from the alkyl radical adduct, the rate constants were 1.7 x 10(7) and 1.6 x 10(8) S(-1), the faster associated with the formation of the E isomer. DFT-BB1K calculations on 2-butene assign this large preference of fragmentation for the E isomer to a lower activation barrier for the formation of the E transition state from the equilibrium radical adduct structure.

Journal Article↗
PubMed2005

Trans fatty acids and atopic eczema/dermatitis syndrome: the relationship with a free radical cis-trans isomerization of membrane lipids.

The formation of trans FA residues in membrane phospholipids may be due to a free radical-catalyzed isomerization process occurring to the cis unsaturated FA moieties. Radical stress is well documented in inflammatory processes of atopic diseases, but no data are yet available about a possible association with trans FA detected in these patients. We investigated the presence of trans lipid isomers in the erythrocyte and T-lymphocyte membranes of 26 children affected by atopic eczema/dermatitis syndrome (AEDS). Trans lipid isomers were found in both cell membranes, up to a total content of 2.7 and 4.9% of the FA composition, respectively. By using the geometrical trans lipid library derived from in vitro models of thiyl radical-catalyzed isomerization, oleic and arachidonic acid isomers were detected. The statistical significance was evaluated by comparison with an age-matched control group. These results suggest the role of an endogenous free radical isomerization path occurring to membrane unsaturated lipids, complementary to the dietary contribution, which can be involved in the lipid impairment in AEDS. This study contributes to lipidomic research regarding the double bond structure and the influence of a geometrical change of membrane lipids in physiology and diseases.

Chromatography, Gas↗
PubMed2005

Trans lipids: the free radical path.

Free radical-catalyzed cis-trans isomerization of unsaturated lipids and its outcome in biomimetic conditions are reviewed. They provided indications for an endogenous origin of trans unsaturated fatty acids in humans by the attack of thiyl radicals. A multidisciplinary approach highlights the relevance of this topic. The role of cis lipid geometry and its maintenance in the biological environment is an emerging question, with future developments in the fields of lipidomics, biology, and medicine.

Free Radicals↗