Free Radical Transformations Research Articles

Metal‐Free C=C Double Bond Cleavage on Enaminones for the Synthesis of α‐Ketoamides by Free‐Radical Aerobic Oxygenation

The tandem oxidation of the enaminone C=C double bond as well as subsequent C‐N bond formation are realized under metal‐free conditions by thermo‐induced free radical transformation. In the presence of benzoyl peroxide (BPO) and N‐iodosuccinimide (NIS), a series of tertiary α‐ketoamides are synthesized practically under aerobic atmosphere. The 18O isotopic experiment confirms that air is the source of oxygen in the newly generated carbonyl group.

Ultrasonic-assisted citrus pectin modification in the bicarbonate-activated hydrogen peroxide system: Chemical and microstructural analysis.

The modified pectin (MP) showed the improved functional properties than the native one. The aim of present study was to develop the ultrasonic accelerated bicarbonate-hydrogen peroxide system for pectin modification to generate short fragments with advanced bioactive properties. The depolymerization effects of this system on the physicochemical properties, structural features, and bioactivity of the degraded fragments were studied systematically. The results indicated that the molecular weight of pectin was reduced drastically from 1088 kDa to 33 kDa within 50 min under an optimized condition (MH2O2-MNaHCO3 = 1:2.5, 50 °C, and ultrasound intensity = 11.4 W/cm3). The resulting fragments also showed lower degree of methoxylation and rheological viscosity. The investigation on the sample structures and active oxygen species demonstrated that the highly active O2- species generated from HCO4- of NaHCO3-H2O2 acted preferentially on the GalA backbone in the HG region, while the RG-I region was maintained; and ultrasound enhanced the degradation efficiency via both chemical effects (increasing the transformation of free radicals) and mechanical effects (disaggregating polysaccharide clusters). The atomic force microscope (AFM) imaging directly verified the branched-chain morphology of pectin and the small-strand degradation fragments. Moreover, ultrasound and NaHCO3-H2O2 treatment induced high galactose content in the degraded products, contributing to an improved inhibitory activity against A549 lung cancer cells, as shown by MTT assay.

ROS-induced lipid transformations without oxygen participation.

This review presents data showing the possibility of novel pathways to be realized for free-radical transformations of glycerophospholipids and sphingolipids. These transformations include the stages of formation and subsequent decay of carbon- and nitrogen-centered radicals of the starting lipids resulting in the accumulation of signal molecules. The presence of a hydroxyl group in the polar component of lipids is a prerequisite for the implementation of these processes. This enables their structural modification and/or destruction to take place with the accumulation of biologically active products such as phosphatidic acid, ceramides, diacylglycerols and acylamides. Sphingolipids containing a free amino group, when interacting with active species of oxygen or chlorine, form aminyl radicals. These lipid radicals undergo further fragmentation, leading to the accumulation of 2-hexadecenal, which has a broad spectrum of biological activity. The presence of an amide group in the structure of sphingolipids determines the possibility of their photodestruction, which also results in the formation of 2-hexadecenal. In contrast with lipid peroxidation, which is inhibited by reducing agents, free-radical fragmentation reactions of hydroxyl-containing lipids involving carbon-centered radicals are blocked by oxidants.

P-51 - Free radical transformations of glucose metabolites in aqueous solutions

It is well known that ROS, generated via various enzymatic and non-enzymatic pathways, can cause the damage of biomolecules. Using γ-irradiation and/or Fe2+/t-BuOOH reagent system for •OH and •OR generation we have shown that glucose metabolites and their analogs (fructose-1,6-bisphosphate, glyceraldehyde-3-phosphate, glycerol-1-phosphate etc.) undergo free radical destruction in aqueous solutions. As a result of such reactions inorganic phosphate and carbonyl products were formed. Among free radical transformation products of starting compounds glyoxal and methylglyoxal (MG) have also been found. The mechanisms for such transformations were proposed. It is known that dicarbonyls possess high toxicity, MG is a potent protein glycating agent, MG-derived hydroimidazolone (MG-H1) is often the major advanced glycation end-product in proteins of tissues and body fluids, increasing in diabetes and associated vascular complications, renal failure, cirrhosis, Alzheimer's disease, arthritis, Parkinson's disease and ageing. The obtained data are recommended to consider during estimation of ROS-induced pathophysiological processes involving glucose metabolites.

P-77 - Effects of azoles on processes involving hydroxyl-containing carbon-centered organic radicals

Free radical fragmentation (FRF) reactions taking place in hydroxyl-containing (HC) biologically relevant substances can make a substantial contribution to the consequences resulting from irradiation of biosystems. HC organic compounds under radiolysis of their aqueous solutions undergo fragmentation that cause damage to carbohydrates, HC lipids and proteins. It has been established earlier that the HC lipids being subjected to radiolysis undergo such fragmentation, giving phosphatidic acid (PA). Accumulation of PA in cancer cells promotes their proliferation. The aforesaid is an important incentive to perform the search for the substances capable of producing an effective regulative action on the probability of FRF reactions occurrence. The object pursued in this study was investigation of the effects produced by azoles on formation of the end products during radiolysis of aqueous solutions of glycerol-1-phosphate (G1F), free radical transformations of that models HC lipids fragmentation. We established ability of nitroazoles to inhibit fragmentation of G1F. This fact open up a new possibility to enhance efficacy of radiation therapy by introducing agents effectively blocking the radiation-induced processes leading to formation of products promoting cancer cell proliferation.

Fe2O3-Promoted Intermolecular Chlorotrifluoromethylthiolation of Alkenes.

A simple, convenient method for intermolecular chlorotrifluoromethylthiolation of alkenes by using a low-cost and more abundant iron catalyst has been developed. This protocol provides a straightforward way to synthesize a variety of useful SCF3-containing chlorides from a wide range of alkenes, including electron-deficient, aromatic, and unactivated alkenes. Mechanistic studies indicate that this is a free radical transformation, and the stronger electrophilic trifluoromethylthiolating reagent CF3SCl was generated in situ under the employed conditions. The synthetic applications of this approach were also explored by a variety of synthetically useful transformations.

P 010 - UV-induced free radical transformations of sphingolipids

Photochemical transformations of membrane lipids can lead to their modification and/or destruction, and consequently cause changes in their biological functions. Among the most studied photoinduced reactions of glycerophospholipids are the processes of lipid oxidation and oxidative degradation. Sphingolipids unlike glycerophospholipids resistant to peroxidation processes. At the same time, these lipids are part of the plasma membranes of skin cells and exposed to UV light. We have sown that direct action of UV irradiation on sphingomyelins in water dispersions induces the Norrish type I decomposition with the formation and subsequence rupture of nitrogen-centered radicals. In the case of sphingosine, containing a free amino group, its photolysis can lead to the photodissociation and formation of N-centered radicals due to n,σ * - transition. The main products of sphingolipids photodestruction were unsaturated aldehydes, which possess a wide spectrum of biological activity. The photolysis of sphingosine and sphingomyelin with the addition of sensitizers expands the range of photolysis products via the possible formation of N- and C-centered radicals. The results of this study can broaden the frontier of research regarding to the mechanisms of photochemical reactions of sphingolipids that may be involved in the development of UV-erythema of the skin, radiation damages.

P 029 - Free radical transformations of hydroxyl-containing amino acids and related compounds in aqueous solutions

It is well known that reactive oxygen species (ROS), generated via various enzymatic and non-enzymatic pathways, can cause the damage of biomolecules. It was established that ROS, interacting with amino acids, initiated mainly their deamination and decarboxylation, the probability of which was largely determined by the molecule structures and their forms in the solutions. Using γ-irradiation for • OH generation we have shown that serine (Ser), threonine (Thr) and related dipeptides as well as glucosamine (GlcN) and 1-amino-2-propanol undergo • OH-induced carbon skeleton destruction in aqueous solutions. It was shown that destruction of Ser and Thr proceeded via formation of N-centered radicals of starting compounds. As a result of such reactions glycine and formaldehyde (or acetaldehyde) were formed. The non-enzymatic free radical Ser conversion, resulting in the formation of glycine and formaldehyde, is similar to the Ser bioconversion driven by serine hydroxymethyltransferase. Among radiolysis products of Ser and Thr in oxygenated solutions glyoxal and methylglyoxal, which are known to possess high toxicity, have been found. The obtained data are recommended to consider during estimation of ROS-induced pathophysiological processes involving such biomoleculs as Ser, Thr and the corresponding peptides as well as GlcN, and, possibly, their complex macromolecular derivatives.

P 006 - Cytochrome c- cardiolipin complex: from peroxidase to Fenton chemistry

The small heme protein cytochrome c (cyt c) has important functions as redox carrier in the mitochondria. While located in the intermembrane space, it is closely associated with the mitochondria-specific lipid cardiolipin (CL). Upon release from stressed mitochondria, cyt c is also involved in apoptosis induction. However, in functioning mitochondria the physiological significance of alterations in cyt c-CL interaction remains largely unknown. Our studies have demonstrated a hydrogen peroxide-dependent iron release from cyt c, which resulted in “Fenton-like” lipid modifications in CL-containing liposomes in the presence of reducing agents, like ascorbic acid or glutathione. By using HPTLC and MALDI-TOF MS we could identify phosphatidic acid and phosphatidylhydroxyacetone as the fragmentation products of free radical transformations of the polar head group of cardiolipin. Moreover, in the hydrophobic part, we observed the formation of CL aldehydes, lyso-CL and lyso-CL aldehydes. The named products could have physiological significance as phosphatidic acid is a secondary messenger in mitochondria, while lyso-CL is involved in the reactions with the apoptosis-related protein tBid. Therefore, our results may suggest a non-enzymatic pathway for the production of CL-derived biologically active compounds.

P 009 - Oxygen levels and free-radical processes in biosystems

Free-radical processes play an important role in functioning of living organisms. The probability of occurrence of the free-radical reactions is significantly affected by oxygen. Depending on the organ type and the nature of tissues and cells, the oxygen levels vary within the range of about 1 to 15%. The diffusion-limited reaction of O 2 with the carbon-centered radicals of biomolecules leads to their oxidation and oxidative destruction, accompanied with formation of cytotoxic products, which is deemed to be the main cause of the damage to the lipids, nucleic acids and proteins. In our studies, we have shown that the radicals formed from hydroxyl-containing molecules under conditions of low oxygen levels undergo various fragmentation reactions before interaction with O 2 takes place. These reactions result in causing damage to the initial substances and formation of bioactive products. Such reactions prevail when the reactive oxygen species interact with hydrocarbons, hydroxyl-containing glycerophospholipids, amino acids, peptides and sphingolipids. In the report, the issues will be discussed associated with the influence of oxygen and the structure of biologically relevant substances on the probability of various free-radical transformations to occur, the possible consequences of such processes and the ways of controlling them.

Lignocellulose-degrading enzymes, free-radical transformations during composting of lignocellulosic waste and biothermal phases in small-scale reactors.

Environmentally friendly strategies of waste management are both part of legal solutions currently in place and a focus of interest worldwide. Large-scale composting plants are set up across various regions while home composting is becoming increasingly popular. A variety of microbial groups are successively at work during composting and enzymatic activities detected in the composting mass fluctuate accordingly. Changes in the activities of oxidoreductases and hydrolases, i.e. glucose oxidase, horseradish peroxidase, lignin peroxidase, laccase, xylanase, superoxide dismutase and keratinase, low-molecular weight compounds, i.e. methoxyphenolic and hydroxyphenolic compounds, and the relative level of superoxide radicals and glucose were determined periodically in water extracts of composts to investigate the process of biochemical transformations of ligninocellulose in relation to biothermal phases and to identify a potential priming effect in two composts containing different ratios of lignocellulosic waste and chicken feathers. Composting was conducted for 30weeks. An important aim of the study was to demonstrate that a positive priming effect was induced during composting of a variety of lignocellulosic waste types using native keratin (chicken feathers) as a source of N. The effect was more evident in compost containing grass, which was related to a more rapid depletion of easily available sources of C and energy (glucose) during composting. Ligninolytic enzymes known to biodegrade recalcitrant organic matter were induced in subsequent biothermal phases of composting. Compost I enriched with grass (pine bark, grass, sawdust and chicken feathers) exhibited a higher enzymatic activity than compost II which did not contain any grass but which had a greater number of hardly-degradable components (pine bark, wheat straw, sawdust, chicken feathers). Similar observations were made for the concentrations of low-molecular weight compounds. The enzymes activities and concentration of low-molecular weight compounds listed above can be used to estimate the biodegradation of lignocellulose during composting.

Influence of lipids with hydroxyl-containing head groups on Fe2+ (Cu2+)/H2O2-mediated transformation of phospholipids in model membranes

Under condition of ROS formation in lipid membranes, free radical reactions can proceed in both hydrophobic (peroxidation of lipids, POL) and polar (free radical fragmentation) parts of the bilayer. Free-radical fragmentation is typical for the lipids containing a hydroxyl group in β-position with respect to an ester or amide bond. The present study has been undertaken to investigate free-radical transformations of phospholipids in model membranes containing lipids able to undergo fragmentation in their polar part. Liposomes from egg yolk lecithin containing saturated or monounsaturated glycero- and sphingolipids were subjected to the action of an HO* – generating system – Fe2+(Cu2+)/H2O2/Asc, and the POL products were investigated. In parallel with this, the effects of monoacylglycerols and scavengers of reactive species on Fe2+(Cu2+)/H2O2/Asc – mediated free-radical fragmentation of phosphatidylglycerols were studied. Hydroxyl-containing sphingolipids and glycerolipids, which undergo free-radical fragmentation under such conditions, manifested antioxidant properties in the model membranes. In the absence of HO groups in the lipid structure, the effect was either pro-oxidant or neutral. Monoacylglycerols slowed down the rate of both peroxidation in the hydrophobic part and free-radical fragmentation in the hydrophilic part of phospholipid membrane. Scavengers of reactive species inhibited the fragmentation of phosphatidylglycerol substantially. Thus, the ability of hydroxyl-containing lipids to undergo free-radical fragmentation in polar part apparently makes a substantial contribution to the mechanism of their protector action.

Towards Streamlining Conventional Radical Reactions Through Development of β-cyclodextrin based Batch, Flow-Through and “Teabag” Prototype Molecular Reactors

β-cyclodextrin based Batch, Flow-Through and “Teabag” Prototype Molecular Reactors have been assembled and used in variety of conventional synthetically useful free radical transformations (Hydrogen Transfer Reactions, Radical Cascade Reactions and Mn(OAc)3 mediated cascade/oxidation reactions. Reactions proceeded smoothly in all cases in good to excellent yields at ambient temperature in aqueous and organic media. The advantages of newly assembled setup are ease of setup, recyclability of the β-cyclodextrin media, flexibility and scope of the transformations to be performed and ease of scale-up of methodology. Keywords: free radical synthesis, molecular reactors, flow through chemistry, tea-bag methodology, streamlining, β-cyclodextrins, Radical chemistry, batch reactors, prototype flow-through, “teabag” molecular reactors

ChemInform Abstract: Thiols as an Efficient Hydrogen Atom Donor in Free Radical Transformations in Aqueous Media

AbstractReview: 62 refs.

Towards use of Floricil-Based Molecular Batch Molecular Reactors for Conventional Free Radical Chemistry

Floricil (60-100nm, activated)-based Batch Molecular Reactors have been assembled and used in a variety of conventional synthetically useful free radical transformations (Hydrogen Transfer Reactions, Radical Cascade Reactions and Addition to C=C and C=N bonds). Reactions proceeded smoothly in all cases in good to excellent yields at ambient temperature in aqueous and organic media. The advantages of newly assembled setup are ease of setup, recyclability of the solid media, flexibility and scope of the transformations to be performed and ease of scale-up of methodology.

On the Scope of Radical Reactions Utilizing InCl3/coreductant as an Efficient Reagent for Synthetically Useful Transformations in Aqueous and Organic Solvents

A broad range of free radical transformations such as hydrogen atom transfer, halogen atom transfer, radical cascade, deoxygenations, and additions to olefins and alkynes have been investigated in the presence of InCl3/coreductant (Bu3SnH, TMS3SiH, H3PO2 or NaBH4) as an efficient hydrogen donor system in water. Reactions proceeded smoothly and in excellent yields, with InCl3 playing a dual role as efficient initiator and hydrogen donor. The approach has expanded the kinetic range, stereospecificity as well as broadened the applicability of the free radical transformations in aqueous media. Mechanistic aspects of described transformations are also addressed. Keywords: Free radicals, indium, aqueous media, synthesis, radicals, InCl3/coreductant, stereo-chemical selectivity, TMS3SiH, Et3B/O2, 1H NMR spectroscopy, MS spectrometry, Organic Solvents, phenol, 1-BrAd, Cl2InH, alkynes

ChemInform Abstract: Radical-Mediated Halogenations of Anomerically N-Substituted Glucopyranosyl Derivatives.

Abstract Reactions of acetylated N-aryl-D-glucosylamines with N-bromosuccinimide-benzoyl peroxide or with sulfuryl chloride-azoisobutyronitrile gave aromatic halo derivatives. The corresponding N-acetylated compounds were mostly inert towards halogenation. Bromination of acetylated cellobiosylpiperidine resulted in the formation of acetobromocellobiose, while the acetylated 2,6,8-trichloro-9-(β-D-glucopyranosyl)-purine was transformed into its 5′-bromo derivative. In contrast, peracetylated glucopyranosyl isothiocyanate or azides, when treated by N-bromosuccinimide under free-radical conditions, essentially undergo an initial homolysis of the anomeric C-H bond which is faster for β-anomers. This initiates a new, simple and efficient free-radical transformation of such sugar azides into an unprecedented brornimino lactone (92% isolated yield).

Thiols as an Efficient Hydrogen Atom Donor in Free Radical Transformations in Aqueous Media

This paper highlights several methods of C-C and C-H transfer reactions in aqueous media. In all cases, thiols play the role of the reducing agents. A variety of useful synthetic methodologies were also described, which occurred mainly via a free radical non-chain transfer processes. The potential usefulness of free radical reactions in water is demonstrated by ever-increasing studies over the last 5 years. In addition, a cis-trans lipid isomerization process under photoand gamma-irradiation conditions was reported. The complexity of the selective generation of thiyl radical in aqueous media and/or in biological milieus makes this topic highly important in chemistry, biology and medicine.

Low-temperature plasma surface modification of textiles made from natural fibers and advanced technologies

Processes that occur in natural fibers during glow-discharge plasma treatment are considered. A study of the plasma etching kinetics, capillarity changes, the fiber surface (using electron microscopy and attenuated total multiple internal reflection IR spectroscopy), and the principal mechanical and other properties demonstrated that modification and degradation affect the fiber surface layers. It is evident that the surface membranes of flax and wool fiber cells are damaged. Important reaction pathways are processes involving the transformations of free radicals. Plasma treatment of gray linen fabric leads to degradation and modification of impurities, thereby opening an opportunity for accelerating the laborious bleaching process and making it environmentally more benign. The enhancement of the sorption-diffusion properties by plasma treatment makes it possible to intensify the dyeing and printing processes.

PolyHIPEs as Novel Media for Conventional Free Radical Chemistry

The novel materials, polyHIPEs with incorporated tetrasubstituted ammonium cationic surfactant (CTAB) have been applied to a broad range of radical precursors in various free radical transformations in organic and aqueous media. The advantage of this reagent/ solid phase surfactant combination lies in its affordability, miniscule toxicity, avoidance of highly toxic “tin based hydrogen donors” under green reaction conditions.