Biomimetic Models for Radical Stress Investigation

Abstract

Free radicals are generated in the biological environment as a result of normal intracellular metabolism. Reactive oxygen species (ROS) function as physiological signalling molecules that participate in the modulation of apoptosis, stress responses and proliferation. ROS can also have a negative effect by causing damages to biomolecules. Therefore, the estimation of the type and extent of damages, as well as the efficiency of the protective and repair systems, is important subjects in life sciences. When studying free radical‐based chemical mechanisms, it is very important to establish biomimetic models, which allow the experiments to be performed in a simplified environment, but suitably designed to be in strict connection with cellular conditions. The biomimetic modelling approach has been coupled with physical organic chemistry methodologies and knowledge of free radical reactivity, in order to gather substantial knowledge on biological processes relevant to health, such as biological damages and repair, signalling and biomarkers, biotechnological applications and novel synthetic approaches.

Key Concepts

  • The overproduction of ROS/RNS has been linked with the aetiology of various diseases.
  • Hydroxyl radicals (HO) can be generated by γ‐radiolysis of neutral water or by Fenton reaction of H2O2.
  • 5′,8‐Cyclopurine lesions result from the chemistry of the C5′ radicals generated by the attack of HO radicals to 2‐deoxyribose units of DNA.
  • 5′,8‐Cyclopurine lesions can be exclusively repaired by nucleotide excision repair (NER) enzyme.
  • Large unilamellar vesicles (LUV) are the closest models to membranes.
  • Mono‐trans isomers of PUFA are biomarkers of endogenous formation by radical stress.
  • Methionine or cysteine residues upon γ‐irradiation produce sulfur‐centred radicals.
  • Bioinspired organic synthesis is based on the mechanism of naturally occurring processes.

Keywords: reactive oxygen species; biomimetic chemistry; gamma‐radiolysis; hydroxyl radical; trans‐fatty acid; liposome; radical stress; tandem lipid‐protein damage; cyclopurine lesion; DNA damage

Figure 1. Molecular pathways of ROS/RNS network includes molecules and radicals in living systems. The main processes that generate HO radicals are the Fenton reaction of H2O2, the reduction of HOCl by superoxide radical anion and the spontaneous decomposition of protonated ONOO, respectively (depicted in black colour). Myeloperoxidase (MPO) catalyse oxidation of halogen anions (Cl, Br) by H2O2, thereby forming the highly reactive hypohalous acids (HOCl, HOBr).
Figure 2. (a) Structures of 5′,8‐cyclo‐2′‐deoxyadenosine (cdA) and 5′,8‐cyclo‐2′‐deoxyguanosine (cdG) in their 5′R and 5′S diastereomeric forms. (b) Fate of the C5′ radical is oxygen‐concentration dependent; when the base is adenine or guanine the radical cyclisation is in competition with the oxygen trapping. Adapted from Chatgilialoglu C, Ferreri C and Terzidis MA (2011a) Purine 5′, 8‐cyclonucleoside lesions: Chemistry and biology. Chemical Society Reviews 40: 1368–1382.
Figure 3. (a) HOCH2CH2S radical‐catalyzed isomerisation of methyl oleate and enthalpy profile in kcal mol−1 for the cis−trans isomerisation of 2‐butene by the HOCH2CH2S radical. (b) Cis−trans isomerisation of PUFA catalysed by thiyl radicals. Adapted from Chatgilialoglu C, Ferreri C, Melchiorre M et al. (2014a) Lipid geometrical isomerism: from chemistry to biology and diagnostics. Chemical Reviews 114: 255–284.
Figure 4. (a) The concept of an ‘integrated vision of protein−lipid damage’, which is relevant for lipidomics and proteomics; (b) Tandem protein−lipid damage under reductive radical stress. Methionine and cysteine (cystine) residues are modified to α‐aminobutyric acid and alanine/cysteine, respectively, by the attack of H and/or eaq. Concomitant formation of diffusible sulfur‐centred radicals (CH3S or S) able to migrate into the lipid bilayer induces the cis−trans isomerisation of unsaturated fatty acid residues. (b) From Chatgilialoglu C, Ferreri C, Melchiorre M et al. (2014a) Lipid geometrical isomerism: from chemistry to biology and diagnostics. Chemical Reviews 114: 255–284.
Figure 5. (a) Transformation of ribonucleotides to 2′‐deoxy‐ribonucleotides by RNR class I; (b) dual catalytic/radical chain mechanism for the conversion of 1,2‐cyclopentanediol to cyclopentanol via cyclopentanone by H2S in aqueous medium under photolytical conditions (HAT, hydrogen, atom transfer; SET, single electron transfer). (b) From Barata‐Vallejo S, Ferreri C, Golding BT et al. (2018) Hydrogen Sulfide: A Reagent for pH‐ Driven Bioinspired 1,2‐Diol Mono‐deoxygenation and Carbonyl Reduction in Water. Organic Letters 20: 4290–4294.
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Further Reading

Chatgilialoglu C, Ferreri C, Torreggiani A, et al. (2011) Radiation‐induced reductive modifications of sulfur‐containing amino acids within peptides and proteins. Journal of Proteomics 74: 2264–2273.

Chatgilialoglu C and Studer A (2012) Encyclopedia of Radicals in Chemistry, Biology and Materials. Wiley: Chichester, UK.

Chatgilialoglu C, Ferreri C, Melchiorre M, et al. (2014) Lipid geometrical isomerism: from chemistry to biology and diagnostics. Chemical Reviews 114: 255–284.

Chatgilialoglu C, Ferreri C and Matyjaszewski K (2016) Radicals and dormant species in biology and polymer chemistry. ChemPlusChem 81: 11–29.

Chatgilialoglu C, Ferreri C, Landais Y, et al. (2018) Thirty years of (TMS)3SiH: a milestone in radical‐based synthetic chemistry. Chemical Reviews 118: 6516–6572.

Chatgilialoglu C, Ferreri C, Geacintov NE, et al. (2019) 5′,8‐cyclopurine lesions in DNA damage: chemical, analytical, biological and diagnostic significance. Cells 8: 513.

Ferreri C and Chatgilialoglu C (2012) Role of fatty acid‐based functional lipidomics in the development of molecular diagnostic tools. Expert Review of Molecular Diagnostics 12: 767–780.

Ferreri C and Chatgilialoglu C (2015) Membrane Lipidomics for Personalized Health. Wiley: Chichester, UK.

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Chatgilialoglu, Chryssostomos, and Barata‐Vallejo, Sebastián(Jun 2020) Biomimetic Models for Radical Stress Investigation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0028844]