Biomimetic Radical Chemistry and Applications

The enormous importance of free radical chemistry for a variety of biological events, including ageing and inflammation, has attracted a strong interest in understanding the related mechanistic steps at the molecular level. Modelling the free radical chemical reactivity of biological systems is an important research area. When studying free-radical-based chemical mechanisms, biomimetic chemistry and the design of established biomimetic models come into play to perform experiments in a controlled environment that is suitably designed to be in strict connection with cellular conditions. This Special Issue gives the reader a wide overview of biomimetic radical chemistry, where molecular mechanisms have been defined and molecular libraries of products are developed to also be used as traces for the discovery of some relevant biological processes. Several subjects are presented, with 12 articles and 6 reviews written by specialists in the fields of DNA, proteins, lipids, biotechnological applications, and bioinspired synthesis, having “free radicals” as a common denominator

The influence of antioxidants in the thiyl radical induced lipid peroxidation and geometrical isomerization in micelles of linoleic acid

The biomimetic model of micelles of linoleic acid containing 2-mercaptoethanol and the antioxidant was examined under gamma irradiation up to 400 Gy in aerobic or deoxygenated conditions where thiyl radicals are the main reactive species. Lipid peroxidation was retarded by ascorbic acid and α-tocopherol, whereas this process was strongly inhibited by resveratrol as effectively as the ascorbic acid/α-tocopherol mixture. Furthermore, antioxidants have a much stronger inhibitory effect on the peroxidation in the presence of 2-mercaptoethanol, and at the same time show protective properties of the double bond, decreasing the cis–trans isomerization. Under anaerobic conditions cis–trans isomerization occurred and antioxidants efficiency increased along the series: resveratrol α-tocopherol ascorbic acid. This result is explained taking into account the double bond localization in the hydrophobic core of the micelle and the need of co- localization of the antioxidant in order to get an anti-isomerizing activity and protection of the natural lipid geometry

Bleomycin-induced trans lipid formation in cell membranes and in liposome models

Cell cultures of NTera-2 cells incubated with bleomycin and liposomes as biomimetic models of cell membranes were used for examining some novel aspects of drug-metal induced reactivity with unsaturated lipids under oxidative conditions. In cell cultures, bleomycin was found for the first time to cause the formation of trans fatty acids. The chemical basis of this transformation was ascertained by liposome experiments, using bleomycin-iron complexes in the presence of thiol as a reducing agent that by incubation at 37 °C gave rise to the thiyl radical-catalysed double bond isomerisation of membrane phospholipids. The effect of oxygen and reagent concentrations on the reaction outcome was studied. An interesting scenario of free radical reactivity is proposed, which can be relevant for understanding the role of membrane lipids in antitumoral treatments and drug carrier interaction.Fil: Cort, Aysegul. Akdeniz University. Faculty of Medicine; Turquía. Consiglio Nazionale delle Ricerche; ItaliaFil: Ozben, Tomris. Akdeniz University. Faculty of Medicine; TurquíaFil: Sansone, Anna. Consiglio Nazionale delle Ricerche; ItaliaFil: Barata Vallejo, Sebastian. Consiglio Nazionale delle Ricerche; Italia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chatgilialoglu, Chryssostomos. Demokritos National Centre For Scientific Research; GreciaFil: Ferreri, Carla. Consiglio Nazionale delle Ricerche; Itali

Lipid geometrical isomerism: from chemistry to biology and diagnostics.

Lipidomics, the discipline regarding chemical and metabolic lipid fates in living organisms, has brought about a successful innovation to lipid research. Expansion of trans lipid research can be easily foreseen in analytics, chemical mechanisms, liposome and oil technology, lipidomics, and diagnostics. Innovative fields can also include the design of molecular switches, taking advantage of the different sensitivity of trans- and cis-containing membranes to physical and chemical stimuli, as well as the determination of biological and pharmacological strategies based on the tunable molecular interactions produced by the exchange of the natural cis with the unnatural trans geometry. The presence of trans lipids in membranes also has a profound influence on temperature sensitivity as tested by insertion of a probe sensitive to the lipid environment, such as cis-parinaric acid, using accurate stopped-flow fluorescence measurements

Revisiting the reaction of hydroxyl radicals with vicinal diols in water

The carbonyl products of the reactions of hydroxyl radicals with three vicinal diols (ethane-1,2-diol, propane-1,2-diol and butane-2,3-diol) have been identified and quantified. Hydroxyl radicals were produced by gamma-radiolysis of N2O-saturated aqueous solutions. The reactions result in the formation of alkoxyl radicals (15%) followed by beta-fragmentation, and alpha-hydroxyl alkyl radicals that undergo H2O elimination. The latter process is part of a radical chain reaction at higher diol concentrations.Fil: Jiang, Dong. University of Newcastle; Reino UnidoFil: Barata Vallejo, Sebastian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica. Cátedra de Química Orgánica I; ArgentinaFil: Golding, Bernard T.. University of Newcastle; Reino UnidoFil: Ferreri, Carla. Consiglio Nazionale delle Ricerche; ItaliaFil: Chatgilialoglu, Chryssostomos. Consiglio Nazionale delle Ricerche; Itali

Converging fate of the oxidation and reduction of 8-thioguanosine

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.Fil: Taras Goslinska, Katarzyna. Adam Mickiewicz University; PoloniaFil: Vetica, Fabrizio. Consiglio Nazionale delle Ricerche; ItaliaFil: Barata Vallejo, Sebastian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Triantakostanti, Virginia. Consiglio Nazionale delle Ricerche; ItaliaFil: Marciniak, Bronislaw. Adam Mickiewicz University; PoloniaFil: Chatgilialoglu, Chryssostomos. Consiglio Nazionale delle Ricerche; Itali

Lipidomics and Free Radical Modifications of Lipids

The free-radical-induced modification of biologically relevant molecules is an active field of interdisciplinary research, spanning from chemistry to biochemistry, biology and medicine. Lipid modifications are also attracting attention for their relationship with structural and functional roles in physiological and pathological conditions of living organisms. The discipline of lipidomics studies the lipid behavior in an innovative and multidisciplinary context. Combining lipidomics with free radical chemistry, the research field becomes an ideal setting for the chemical biology approach, to study the basis of molecular mechanisms and chemical reactivity and connect them with free-radical-based processes occurring in the biological environment. This paper will give an overview of the approaches for studying free radical processes on lipids and some biological consequences, which represent also subjects of interdisciplinary collaborations among European research groups and contribute to the general topic of the COST Action 'Free Radicals in Chemical Biology'

A 5\u27, 8-cyclo-2\u27-deoxypurine lesion induces trinucleotide repeat deletion via a unique lesion bypass by DNA polymerase β.

5′,8-cyclo-2′-deoxypurines (cdPus) are common forms of oxidized DNA lesions resulting from endogenous and environmental oxidative stress such as ionizing radiation. The lesions can only be repaired by nucleotide excision repair with a low efficiency. This results in their accumulation in the genome that leads to stalling of the replication DNA polymerases and poor lesion bypass by translesion DNA polymerases. Trinucleotide repeats (TNRs) consist of tandem repeats of Gs and As and therefore are hotspots of cdPus. In this study, we provided the first evidence that both (5′R)- and (5′S)-5′,8-cyclo-2′-deoxyadenosine (cdA) in a CAG repeat tract caused CTG repeat deletion exclusively during DNA lagging strand maturation and base excision repair. We found that a cdA induced the formation of a CAG loop in the template strand, which was skipped over by DNA polymerase β (pol β) lesion bypass synthesis. This subsequently resulted in the formation of a long flap that was efficiently cleaved by flap endonuclease 1, thereby leading to repeat deletion. Our study indicates that accumulation of cdPus in the human genome can lead to TNR instability via a unique lesion bypass by pol β