Chatgilialoglu C. (ed.) Biomimetic Radical Chemistry and Applications

Basel, MDPI, 2020. - 300 p.
Free radicals have attracted considerable attention in various research areas, including organic synthesis, material science, atmospheric chemistry, radiation chemistry, pharmacology, biology, and medicine. The “free radical theory of aging”, the role of enzymes like superoxide dismutase (SOD) or ribonucleotide reductase (RNR), the antioxidant network, and the role of vitamins are now milestones of the life sciences. Free radicals are generated in the biological environment as a result of normal intracellular metabolism and function as physiological signaling molecules that participate in the modulation of apoptosis, stress responses, and proliferation. During inflammatory response, their concentrations can increase up to 100-fold excess, and if not properly quenched, they can have a negative effect by causing damages to biomolecules. Therefore, the estimation of the type and extent of damages, as well as the mechanisms and efficiency of protective and repair systems, are important subjects in the life sciences.
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, suitably designed to be in strict connection with cellular conditions. In this Special Issue, the biomimetic approach is presented with new insights and reviews of the current knowledge in the field of radical-based processes relevant to health, such as biomolecular damages and repair, signaling and biomarkers, biotechnological applications, and novel synthetic approaches. Several subjects are presented, with 12 articles and 6 reviews written by specialists in the fields.
In the area of DNA, the Special Issue reports on: (i) new insights into the reaction of hydroxyl radicals with genetic material and the role of purine lesions as biomarkers; (ii) guanine radicals generated in single, double, and G-quadruplex oligonucleotides studied by nanosecond transient absorption spectroscopy; (iii) an overview of work on the dynamics of hope transfer in DNA; (iv) the mechanism of copper artificial metallo-nuclease to induce superoxide-mediated cleavage via the minor groove; (v) the influence of the type of halogen atom in the radiosensitizing properties of substituted uridines; (vi) an overview of replication stress and the consequential instability of the genome and epigenome.
In the area of proteins, two important reviews deal with the chemical labelling of proteins using biomimetic radical chemistry and the role of thiyl radical reactions in the degradation of protein pharmaceuticals. New insights on mechanistic studies of a mononuclear non-heme oxoiron(IV) complex in aqueous solution as catalase-like activity are also described in an original article. In the area of membrane lipids, two reviews provide thorough descriptions of the role of phosphatidylethanolamine-derived adducts as mediators of reactive aldehydes and effects on membrane properties, and the combination of various technologies to study stress-induced lipid turnover in subcellular organelles of pancreatic beta cells. Biotechnological applications in this Special Issue concern two fields: (i) the entrapment of somatostatin in lipid formulation with the discovery of a new radical reactivity arising from the sulfur-containing peptides and its nanodelivery formulation; (ii) the formation and stabilization of gold nanoparticles in bovine serum albumin solution.
Mechanistic studies of radical processes in pharmacological applications, which also inspire biological mechanisms, are represented by various articles: the oxidation of 8-thioguanosine and 2-thiouracil by photolytic and radiolytic conditions; bioinspired synthetic strategies radical-based toward anomeric spironucleosides as potential inhibitors of glycogen phosphorylase and for the preparation of azido-derivatives via a radical azidoalkylation of alkenes; synthesis of two new iron-porphyrin-based catalysts inspired by naturally occurring proteins such as horseradish peroxidase, hemoglobin, and cytochrome P450 tested for atom transfer radical polymerization (ATRP), obtaining polymers with specific properties.
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. The biomimetic approach is a convenient tool, since the achievements in free radical mechanisms can be easily transferred to a better comprehension of the radical-based biological pathways in living organisms, to foster advancements in health and diseases. In addition, the identification of modified biomolecules paves the way for molecular libraries and the evaluation of in vivo damage through biomarkers.New Insights into the Reaction Paths of Hydroxyl Radicals with Purine Moieties in DNA and Double Stranded Oligodeoxynucleotides
Populations and Dynamics of Guanine Radicals in DNA strands—Direct versus Indirect Generation
The Dynamics of Hole Transfer in DNA
Copper bis-Dipyridoquinoxaline Is a Potent DNA Intercalator that Induces Superoxide-Mediated Cleavage via the Minor Groove
Why Does the Type of Halogen Atom Matter for the Radiosensitizing Properties of 5-Halogen Substituted 4-Thio-2_-Deoxyuridines?
Replication Stress and Consequential Instability of the Genome and Epigenome
Protein Chemical Labeling Using Biomimetic Radical Chemistry
Thiyl Radical Reactions in the Chemical Degradation of Pharmaceutical Proteins
Stability and Catalase-Like Activity of a Mononuclear Non-Heme Oxoiron(IV) Complex in Aqueous Solution
The Role of Phosphatidylethanolamine Adducts in Modification of the Activity of Membrane Proteins under Oxidative Stress
The Combination of Whole Cell Lipidomics Analysis and Single Cell Confocal Imaging of Fluidity and Micropolarity Provides Insight into Stress-Induced Lipid Turnover in Subcellular Organelles of Pancreatic Beta Cells
The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity
Formation and Stabilization of Gold Nanoparticles in Bovine Serum Albumin Solution
Converging Fate of the Oxidation and Reduction of 8-Thioguanosine
Radiation Induced One-Electron Oxidation of 2-Thiouracil in Aqueous Solutions
Anomeric Spironucleosides of β-D-Glucopyranosyl Uracil as Potential Inhibitors of Glycogen Phosphorylase
Two-Step Azidoalkenylation of Terminal Alkenes Using Iodomethyl Sulfones
Axially Ligated Mesohemins as Bio-Mimicking Catalysts for Atom Transfer Radical Polymerization