Radiation Chemical Studies Research Articles

Radiation Chemistry and Radiation Research: A History from the Beginning to the Platinum Edition.

At the dawn of the 20th Century, the underlying chemistry that produced the observed effects of ionizing radiation, e.g., X rays and Radium salts, on aqueous solutions was either unknown or restricted to products found postirradiation. For example, the Curies noted that sealed aqueous solutions of Radium inexplicably decomposed over time, even when kept in the dark. By 1928 there were numerous papers describing the phenomenological effects of ionizing radiation on a wide variety of materials, including the irradiated hands of early radiologists. One scientist who became intensely interested in these radiation effects was Hugo Fricke (Fricke Dosimetry) who established a laboratory in 1928 dedicated to studies on chemical effects of radiation, the results of which he believed were necessary to understand observed radiobiological effects. In this Platinum Issue of Radiation Research (70 years of continuous publication), we present the early history of the development of radiation chemistry and its contributions to all levels of mechanistic radiobiology. We summarize its development as one of the four disciplinary pillars of the Radiation Research Society and its Journal, Radiation Research, founded during the period 1952-1954. In addition, the work of scientists who contributed substantially to the discipline of Radiation Chemistry and to the birth, life and culture of the Society and its journal is presented. In the years following 1954, the increasing knowledge about the underlying temporal and spatial properties of the species produced by various types of radiation is summarized and related to its radiobiology and to modern technologies (e.g., pulsed radiolysis, electron paramagnetic resonance) which became available as the discipline of radiation chemistry developed. A summary of important results from these studies on Radiation Chemistry/Biochemistry in the 20th and 21st Century up to the present time is presented. Finally, we look into the future to see what possible directions radiation chemistry studies might take, based upon promising current research. We find at least two possible directions that will need radiation chemistry expertise to ensure proper experimental design and interpretation of data. These are FLASH radiotherapy, and mechanisms underlying the effects of low doses of radiation delivered at low dose rates. Examples of how radiation chemists could provide beneficial input to these studies are provided.

Radiosensitization of PC3 Prostate Cancer Cells by 5-Thiocyanato-2'-deoxyuridine.

Simple SummaryRadiation therapy is one of the main treatments for cancer. However, the success of treatment by radiation therapy is largely dependent on tumor radiosensitivity. To improve therapeutic outcomes, radiation therapy should be combined with the use of a radiosensitizer which enables irradiation at lower doses with higher efficacies. 5-Thiocyanato-2′-deoxyuridine has been reported as a potential radiosensitizer of DNA damage based on advanced radiation chemical studies. In this paper, for the first time, we demonstrate the radiosensitizing properties of this modified nucleoside at the cellular level. The tested analogue increases the sensitivity of prostate cancer cells to ionizing radiation which is, at least partially, related to an increase in the number of DNA double-strand breaks and cell cycle regulation.Purpose: The radiosensitizing properties of uracil analogs modified in the C5 position are very interesting in the context of their effectiveness and safety in radiation therapy. Recently, radiation chemical studies have confirmed that 5-thiocyanato-2′-deoxyuridine (SCNdU) undergoes dissociation induced by an excess electron attachment and established this nucleoside as a potential radiosensitizer. In this paper, we verify the sensitizing properties of SCNdU at the cellular level and prove that it can effectively enhance ionizing radiation-induced cellular death. Methods and Materials: Prostate cancer cells were treated with SCNdU and irradiated with X rays. The cytotoxicity of SCNdU was determined by MTT test. Cell proliferation was assessed using a clonogenic assay. Cell cycle analyses, DNA damage, and cell death analyses were performed by flow cytometry. Results: SCNdU treatment significantly suppressed the proliferation and increased the radiosensitivity of prostate cancer cells. The radiosensitizing effect expressed by the dose enhancement factor is equal to 1.69. Simultaneous exposure of cells to SCNdU and radiation causes an increase in the fraction of the most radiosensitive G2/M phase, enhancement of the histone H2A.X phosphorylation level, and apoptosis induction. Finally, SCNdU turned out to be marginally cytotoxic in the absence of ionizing radiation. Conclusions: Our findings indicate that SCNdU treatment enhances the radiosensitivity of prostate cancer cells in a manner associated with the cell cycle regulation, double strand formation, and a slight induction of apoptosis.

Spectral Probe for Electron Transfer and Addition Reactions of Azide Radicals with Substituted Quinoxalin-2-Ones in Aqueous Solutions.

The azide radical (N3●) is one of the most important one-electron oxidants used extensively in radiation chemistry studies involving molecules of biological significance. Generally, it was assumed that N3● reacts in aqueous solutions only by electron transfer. However, there were several reports indicating the possibility of N3● addition in aqueous solutions to organic compounds containing double bonds. The main purpose of this study was to find an experimental approach that allows a clear assignment of the nature of obtained products either to its one-electron oxidation or its addition products. Radiolysis of water provides a convenient source of one-electron oxidizing radicals characterized by a very broad range of reduction potentials. Two inorganic radicals (SO4●−, CO3●−) and Tl2+ ions with the reduction potentials higher, and one radical (SCN)2●− with the reduction potential slightly lower than the reduction potential of N3● were selected as dominant electron-acceptors. Transient absorption spectra formed in their reactions with a series of quinoxalin-2-one derivatives were confronted with absorption spectra formed from reactions of N3● with the same series of compounds. Cases, in which the absorption spectra formed in reactions involving N3● differ from the absorption spectra formed in the reactions involving other one-electron oxidants, strongly indicate that N3● is involved in the other reaction channel such as addition to double bonds. Moreover, it was shown that high-rate constants of reactions of N3● with quinoxalin-2-ones do not ultimately prove that they are electron transfer reactions. The optimized structures of the radical cations (7-R-3-MeQ)●+, radicals (7-R-3-MeQ)● and N3● adducts at the C2 carbon atom in pyrazine moiety and their absorption spectra are reasonably well reproduced by density functional theory quantum mechanics calculations employing the ωB97XD functional combined with the Dunning’s aug-cc-pVTZ correlation-consistent polarized basis sets augmented with diffuse functions.

Formation of two centre three electron bond by hydroxyl radical induced reaction of thiocoumarin: evidence from experimental and theoretical studies

Radiation chemical studies of thioesculetin (1), a thioketone derivative of coumarin, were performed by both pulse radiolysis technique and DFT calculations. Hydroxyl (•OH) radical reaction with 1 resulted transients absorbing at 320, 360 and 500 nm. To identify the nature of the transients, the reaction was studied with specific one-electron oxidant (N3•) radical, where 360 nm band was absent. The transient absorption at 500 nm was concentration-dependent. The overall impression for •OH radical reaction was that the transient absorbing at 320, 360 and 500 nm was due to sulphur centred monomer radical, hydroxysulfuranyl and dimer radical of 1 respectively. The equilibrium constant between the monomer to dimer radical was 3.75 × 104 M−1. From the transients’ redox nature, it was observed that 57 and 24% of •OH radical yielded to oxidising and reducing products respectively. Further, the product analysis by HPLC suggested that the dimer radical disproportionate to esculetin and thioesculetin. DFT energy calculation for all the possible transients revealed that dimer radical has the lowest energy. The HOMO of 1 and its monomer radical suggested that the electron density was localised on the sulphur atom. The bond length between the two sulphur atoms in dimer radical was 2.88 Å which was less than the van der Waals distance. Bond order between the two sulphur atoms was 0.55, suggesting that the bond was two centre three electron (2c–3e). From TD-DFT calculation, the electronic transition of dimer radical was at 479 nm which was in close agreement with the experimental value. The nature of the electronic transition was σ → σ* from a 2c − 3e bond.

Can radiation chemistry supply a highly efficient AO(R)P process for organics removal from drinking and waste water? A review.

The increasing role of chemistry in industrial production and its direct and indirect impacts in everyday life create the need for continuous search and efficiency improvement of new methods for decomposition/removal of different classes of waterborne anthropogenic pollutants. This review paper addresses a highly promising class of water treatment solutions, aimed at tackling the pressing problem of emerging contaminants in natural and drinking waters and wastewater discharges. Radiation processing, a technology originating from radiation chemistry studies, has shown encouraging results in the treatment of (mainly) organic water pollution. Radiation ("high energy") processing is an additive-free technology using short-lived reactive species formed by the radiolysis of water, both oxidative and reducing, to carry out decomposition of organic pollutants. The paper illustrates the basic principles of radiolytic treatment of organic pollutants in water and wastewaters and specifically of one of its most practical implementations (electron beam processing). Application examples, highlighting the technology's strong points and operational conditions are described, and a discussion on the possible future of this technology follows.

Extraction of 211At from nitric acid solutions into various organic solvents for use as an α-source for radiation chemistry studies

The partitioning of At-211 from an irradiated bismuth target using solvent extraction into several organic solvents is presented. Although astatine speciation is difficult to measure given its invariably low chemical concentration its extraction here is consistent with the existence of a cationic species in nitric acid that is not reduced upon contact with the organic phase. This is consistent with previous work that postulated the most probable species in acidic solution as AtO+. The technique presented has a simple experimental set up and provides high specific activity astatine solutions compatible for use in alpha-radiolysis studies.

Radiation chemical studies of Gly-Met-Gly in aqueous solution

Important biological consequences are related to the reaction of HO• radicals with methionine (Met). Several fundamental aspects remain to be defined when Met is an amino acid residue incorporated in the interior of peptides and proteins. The present study focuses on Gly-Met-Gly, the simplest peptide where Met is not a terminal residue. The reactions of HO• with Gly-Met-Gly and its N-acetyl derivative were studied by pulse radiolysis technique. The transient absorption spectra were resolved into contributions from specific components of radical intermediates. Moreover, a detailed product analysis is provided for the first time for Met-containing peptides in radiolytic studies to support the mechanistic proposal. By parallel radiolytical and electrochemical reactions and consequent product identification, the formation of sulfoxide attributed to the direct HO• radical attack on the sulfide functionality of the Met residue could be excluded, with the in situ generated hydrogen peroxide responsible for this oxidation. LC–MS and high resolution MS/MS were powerful analytical tools to envisage the structures of five products, thus allowing to complete the mechanistic picture of the overall Met-containing peptide reactivity.

Reactivity pattern of bromonucleosides induced by 2-hydroxypropyl radicals: photochemical, radiation chemical, and computational studies.

The bromonucleosides (BrdX's) 5-bromo-2'-deoxyuridine (BrdU), 5-bromo-2'-deoxycytidine (BrdC), 8-bromo-2'-deoxyadenosine (BrdA), and 5-bromo-2'-deoxyguanosine (BrdG) may substitute for ordinary nucleosides in DNA. As indicated by electron-stimulated desorption experiments, such a modified biopolymer is greater than 2-3-fold more sensitive to damage induced by excess electrons. The other major product of water radiolysis, the (•)OH radical, may form a number of other radicals in chemical reactions with the complex content of the cell. Thus, the well-proved BrdU-labeled DNA radiosensitivity may be, at least in part, related to secondary organic radicals. Therefore, in the current study, the propensity of BrdX's to damage induced by 2-hydroxypropyl radical (OHisop(•))-a prototype radical species-was investigated. The HPLC and LC-MS analyses revealed the formation of two major products from the brominated pyrimidine nucleosides, a native nucleoside and an adduct of BrdX and OHisop(•) , and only an adduct of BrdX from the bromopurine nucleosides. Quantum chemical calculations ascribed this evident difference between purines and pyrimidines to the electron transfer from OHisop(•) to BrdX that is especially favorable in pyrimidines.

Radiation damage to nucleoprotein complexes in macromolecular crystallography.

Significant progress has been made in macromolecular crystallography over recent years in both the understanding and mitigation of X-ray induced radiation damage when collecting diffraction data from crystalline proteins. In contrast, despite the large field that is productively engaged in the study of radiation chemistry of nucleic acids, particularly of DNA, there are currently very few X-ray crystallographic studies on radiation damage mechanisms in nucleic acids. Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under the same controlled conditions. Here a model protein-DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07-44.63 MGy). In order to allow a quantitative analysis of radiation damage sites from a complex series of macromolecular diffraction data, a computational method has been developed that is generally applicable to the field. Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N1-C and sugar-phosphate C-O bonds. Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. At low doses the protein was observed to be susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses.

Sucrose as a dosimetric material for photon and heavy particle radiation: A review

Abstract The application of high-energy radiation in many areas of human activity and its harmful effects on human health makes necessary knowledge of the radiation chemistry of various materials upon exposure to high-energy radiation. Among these materials, saccharides (particularly sucrose) maintain the greatest advantage for potential radiochemistry applications. Until now, radiation chemistry studies have been conducted primarily with γ-ray irradiation; however, in the past few years there has been increased interest in the fields of radiotherapy and radiochemistry on substances irradiated with heavy particles. To this end, this review discusses the possibilities of employing sucrose as a radiation-sensitive material for the determination of absorbed doses of high-energy radiation both for emergency situations and for dosimeters used in standard applications.

Radicals and radical cations of thioacetamide and thiobenzamide in aqueous sulfuric acid media

Studies on the radical cations and radicals of thioacetamide [(CH3)(NH2)C=S] and thiobenzamide [(C6H5)(NH2)C=S], in aqueous sulfuric acid media of various strengths were carried out using pulse radiolysis technique. In this system, the formation time of thioacetamide/thiobenzamide radical cation was observed to be different at different acid strengths. At acid system of pH/H0 = −3.5, the slow growth kinetics signifies a dominating reaction of SO4•− radical with these solutes (reaction rate constants found in the range of 1–4 × 108 M−1 s−1). Two different reactions (solute molecule with •OH and SO4•−) lead to the formation of lone intermediate species (radical cation) following immediate (fast) and delayed (slow) kinetics. By this process, the transient yield increased by 65 % (as the transients’ absorbance at 400 nm increased to 0.090 from 0.055) in the case of thiobenzamide, whereas in the case of thioacetamide, this figure was higher. The general mechanism for the formation of radical cations of these solutes during radiation chemical studies has been revisited wherein the electron transfer reactions are more favorable.

Recent photo- and radiation chemical studies of sulfur radical cations

The chemistry of sulfur radical cations has continued to attract considerable interest in recent years, not only for its practical and theoretical aspects but also for its important biological impl...

Radiation and Quantum Chemical Studies of Chalcone Derivatives

The reactions of oxidizing radicals ((*)OH, Br(2)(*-), and SO(4)(*-)) with -OH-, -CH(3)-, or -NH(2)-substituted indole chalcones and hydroxy benzenoid chalcones were studied by radiation and quantum chemical methods. The (*)OH radical was found to react by addition at diffusion-controlled rates (k = 1.1-1.7 x 10(10) dm(3) mol(-1) s(-1)), but Br(2)(*-) radical reacted by 2 orders of magnitude lower. Quantum chemical calculations at the B3LYP/6-31+G(d,p) level of theory have shown that the (C2-OH)(*), (C11-OH)(*), and (C10-OH)(*) adducts of the indole chalcones and the (C7-OH)(*) and (C8-OH)(*) adducts of the hydroxy benzenoid chalcones are more stable with DeltaH = -39 to -28 kcal mol(-1) and DeltaG = -32 to -19 kcal mol(-1). This suggests that (*)OH addition to the alpha,beta-unsaturated bond is a major reaction channel in both types of chalcones and is barrierless. The stability and lack of dehydration of the (*)OH adducts arise from two factors: strong frontier orbital interaction due to the low energy gap between interacting orbitals and the negligible Coulombic repulsion due to small absolute values of Mulliken charges. The transient absorption spectrum measured in the (*)OH radical reaction with all the indole chalcone derivatives exhibited a maximum at 390 nm, which is in excellent agreement with the computed value (394 nm). The formation of three phenolic products under steady-state radiolysis is in line with the three stable (*)OH adducts predicted by theory. Independent of the substituent, identical spectra (lambda(max) = 330-360 and approximately 580 nm) were obtained on one-electron oxidation of the three indole chalcones. MO calculations predict the deprotonation from the -NH group is more efficient than from the substituent due to the larger electron density on the N1 atom forming the chalcone indolyl radical. Its reduction potential was determined to be 0.56 V from the ABTS(*-)/ABTS(2-) couple. In benzenoid chalcones, the (*)OH adduct spectrum is characterized by a peak at 270 nm and a broad maximum centered in the range 430-450 nm with an intense bleaching at 340 nm. The spectrum formed by electron transfer in these derivatives with lambda(max) = 280 and 380 nm (epsilon(280) = 5000 dm(3) mol(-1) cm(-1) and epsilon(380) = 700 dm(3) mol(-1) cm(-1)) was assigned to its phenoxyl radical. Our pulse radiolysis experiments in combination with quantum chemical calculations demonstrate that chalcones are efficient scavengers of damaging oxyl radicals.

A brief account on radiation chemical studies of antioxidants : Examples from natural phenols, sulfur and selenium compounds

Reactive oxygen species (ROS) is a collective term used for a group of oxidants, which are either free radicals or molecular species capable of generating free radicals. Excessive production of ROS in living cells is a pathological condition known as oxidative stress. These species, depending on their reactivity and oxidizing ability, participate in a variety of chemical reactions and their reactions often cause irreversible chemical changes in biomolecules. Antioxidants are employed to protect the biomolecules from the damaging effects of such free radicals, primarily by their direct reaction. Although free radical reactions involving ROS with antioxidants are studied by several indirect methods, their direct monitoring is possible only by employing fast kinetic methods. Radiation chemistry of aqueous solutions and pulse radiolysis technique in particular has been found to be well suited to probe such reactions. Thus in this article, contributions from radiation chemistry section of BARC on the reactions of biologically important free radicals involved in oxidative stress with antioxidants have been discussed. Reactions of such radicals with curcumin, an antioxidant from turmeric, which was studied extensively in this laboratory using pulse radiolysis technique, has also been presented. In the last three decades, the section has contributed significantly to the understanding of sulfur and selenium based antioxidants. A few recent highlights on these systems using pulse radiolysis have also been compared.

Radiation Chemical Studies of Methionine in Aqueous Solution: Understanding the Role of Molecular Oxygen

The oxidation of methionine is an important reaction in the biological milieu. Despite a few decades of intense studies, several fundamental aspects remain to be defined. We have investigated in detail the gamma-radiolysis of free methionine in the absence and presence of molecular oxygen followed by product characterization and quantification. The primary site of attack by HO(*) radicals and H(*) atoms is the sulfur atom of methionine. We have disclosed that HO(*) radicals do not oxidize methionine to the corresponding sulfoxide in either the presence or the absence of oxygen; the oxidizing species is H(2)O(2) derived either from the radiolysis of water or from the disproportionation of the byproduct O(2)(*-). 3-Methylthiopropionaldehyde is the major product of HO(*) radical attack in the presence of molecular oxygen. Together with the direct oxidation at sulfur as the major product, the potential of H(*) atoms is also proven to be highly specific for sulfur atom attack under anoxic and aerobic conditions. The major products derived from the H(*) atoms attack are found to be alpha-aminobutyric acid or homoserine, in the absence or presence of oxygen, respectively. All together, these results help clarify the fate of methionine related to a biological environment and offer a molecular basis for envisaging other possible pathways of in vivo degradation as well as other markers.

The importance of radiation chemistry to radiation and free radical biology (The 2008 Silvanus Thompson Memorial Lecture)

Biological effects of radiation are manifest over timescales extending to years. However, many chemical events are complete in milliseconds; after this time, adding oxygen to irradiated hypoxic cells no longer enhances radiosensitivity. This does not mean that damage pathways cannot be modified; the potential gain from chemical modulation of early events is as large as any associated with later pathways, and the prognostic importance of variations in levels of small molecules active in fast free radical pathways is as important as any associated with genetic make-up. Reactive oxygen species are much invoked in the wider context, but are frequently undefined and seldom measured unambiguously. Radiation chemistry has much to offer to both radiation and free radical biology. An appreciation of the interlinked parameters of time, spatial distribution and yield is well developed, as are methods to generate specific radicals in known concentrations and to monitor their reactions directly. Intense clinical interest in the 1980s in hypoxic cell radiosensitizers, developed from radiation chemical studies, has waned, but the goal of eliminating hypoxic radioresistance remains attractive. Nitric oxide may be more important than oxygen in determining hypoxic radiosensitivity, and radiation chemistry provides the tools to understand the mechanisms and the limitations of in vitro models. Imaging hypoxia in tumours relies heavily on free radical chemistry and radiolysis methods to understand the mechanistic basis for diagnostic agents. Quantitation of the chemical reactivity of free radicals is a cornerstone of radiation chemistry via the language, concepts and mathematics of chemical kinetics, which are equally applicable to understanding the molecular pathways in radiobiology.

Pulse radiolysis in water with heavy-ion beams. A short review

This article presents a short review of the studies in radiation chemistry of liquid water with heavy ions, which have used pulse radiolysis methods during the last 20 years. The interests and the difficulties of developing this kind of experiment are depicted. The linear energy transfer (LET) effect is the main topic of these studies. The earliest effects close to the structure of the deposited energy can be observed directly by transient absorption spectroscopy by following the hydrated electron, the superoxide radical produced in the absence of molecular oxygen and the hydroxyl radical, which still requires the use of scavenger. Finally, the results can be compared to the heterogeneous chemical processes in the time range of 1 ns to 1 μs described by Monte Carlo simulations. The absolute values of the radiolytic yields are still uncertain because of the dosimetry accuracy. The future aspects of the method are discussed in terms of new types of particle accelerators giving better time resolutions.

Studies in Radiation Chemistry: Application to Ozonation and Other Advanced Oxidation Processes

Advanced oxidation/reduction processes (AORPs) are an alternative water treatment that is becoming more widely utilized. Our radiation-chemistry based studies are being used to develop a fundamental understanding of AOP treatment options, and are divided into three complementary types of contaminants; disinfection by-products (DBPs), emerging pollutants of concern (EPoCs), and natural organic matter (NOM). More than 600 DBPs have been identified, and one class that appears to have severe potential adverse health effects is the halonitromethanes (HNMs). Of the nine HNMs, trichloronitromethane (chloropicrin) is the most common, with levels up to 180 nM in US drinking waters. EPoCs are of interest because of their biological activity at low concentrations in water and while the initial focus was on endocrine disruptor chemicals (EDCs) this class has now been expanded to include many other recalcitrant chemicals such as hormones, antibiotics, industrial contaminants, and health care products. Natural organic matter is one of the most common radical scavengers in natural waters and therefore may adversely affect AOPs. Our approach is to study NOM both directly and using model compounds thought to be representative of structural components of this complex material.

Characterization of Gamma Irradiated Ethylene-Norbornene Copolymer using FTIR, UV-Vis and DSC Techniques

Due to their new combination of properties and shortage of the experimental data, the radiolysis of a new class of materials, cyclo-olefin copolymers (COC), which are polymerized from norbornene and ethylene using metallocene catalysts, is of great interest to the study of radiation chemistry and physics of polymeric systems. Ethylene-norbornene copolymer, bare and containing 0.45 wt % of the hindered phenolic type of an antioxidant (IRGANOX 1010) was subjected to gamma irradiation (100, 200 and 500 kGy) in the presence of air and in water. The irradiated copolymer was studied using FTIR, UV-vis spectrophotometric and gel content analysis. The insoluble fraction was formed in copolymer irradiated in water with 500 kGy, in bare 36% and in copolymer with an antioxidant 23%. The radiation induced changes in the molecular structure were correlated to the specific heat capacity and the glass transition temperature measured by DSC method.

Modification of ethylene-norbornene copolymer by Gamma irradiation

The possibility of modifying polyethylene and many other polymers with high energy radiation has led to many useful applications. Due to their new combination of properties and the shortage of experimental data, the radiolysis of a new class of materials, cyclo-olefin copolymers (COC), polymerised from norbornene and ethylene using metallocene catalysts, is of great interest to the study of radiation chemistry and the physics of polymeric systems. Ethylenenorbornene copolymer, pristine and containing an antioxidant were subjected to gamma irradiation in the presence of air and in water. The irradiated copolymer was studied using IR and UV-vis spectrophotometric analysis. The radiation-induced changes in the molecular structure were correlated to changes in the glass transition temperature measured by the DSC method.