A combined EMR and DFT study of radiation-induced defects in sucrose and glucose 1-phosphate

Ionizing radiation induces radicals in organic matter, i.e. molecules with one or more unpaired electrons. This dissertation deals with a detailed study of radicals induced by X-ray radiation in solid sucrose (also known as common household sugar) and in the dipotassium salt of glucose 1-phosphate (K2G1P). The radiation chemistry of these materials is relevant in the context of radiation damage to DNA and (emergency) dosimetry. Next to the actual research results, which will be discussed below, the dissertation contains several, quite extensive chapters of a more general nature. The research strategy employed mainly comprises electron-magnetic-resonance (EMR) measurements (EPR, ENDOR, HYSCORE, …) and theoretical ab-initio calculations based on density functional theory (DFT). Essentially, radical structures are identified and scrutinized by comparing DFT-calculated and experimentally determined EMR parameters. These are the main results with respect to radiation-induced radicals in sucrose: (i) all major stable radiation-induced radicals are characterized and identified. Each of them requires formation of a carbonyl group and scission of the glycosidic bond. (ii) The transformation of the EPR spectrum during the first four hours after RT irradiation is shown to be due to the decay of several semistable species to diamagnetic products. (iii) Six (more) primary radicals (studied by in-situ irradiation at 10 K and subsequent EMR measurements at 10 K) were characterized and three of the four dominant radicals were identified as H-abstracted species. In K2G1P, the radicals present at 77 K after in-situ X-ray irradiation at 77 K were studied. Four radical species were characterized and identified. The dominant radical is chemically identical to one of the major radicals in sucrose and has a broken sugar-phosphate junction. Finally, it was shown, via first-order perturbation theory, that an ambiguity can arise in the determination of hyperfine tensors for low-symmetry paramagnetic centers with S=1/2 and I=1/2 – which can lead to erroneous radical identification. A firm theoretical basis is thus provided for a problem that was since long known to exist, but not always recognized or adequately dealt with in the literature

Role of radicals in UV-initiated postplasma grafting of poly-ε-caprolactone: an electron paramagnetic resonance study

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On the identity of the last known stable radical in X-irradiated sucrose

Identification of radiation-induced radicals in relatively simple molecules is a prerequisite for the understanding of reaction pathways of the radiation chemistry of complex systems. Sucrose presents an additional practical interest as a versatile radiation dosimetric system. In this work, we present a periodic density functional theory study aimed to identify the fourth stable radical species in this carbohydrate. The proposed model is a fragment suspended in the lattice by hydrogen bonds with an unpaired electron at the original C5’ carbon of the fructose unit. It requires a double scission of the ring accompanied by substantial chemical and geometric reorganization

Radiation-induced radical formation in solid state sugars: a review of recent EMR and DFT results

Carbohydrates are important constituents of several biological systems, including DNA, and elucidating their radiation chemistry is therefore of general importance. In particular, sugar radicals play a crucial role in radiation-induced single and double strand breaks in DNA, which can lead to mutations and, finally, cancer. Certain sugars such as sucrose (table sugar) are also promising dosimetric materials. An advanced knowledge of the radiation-induced processes in carbohydrates may therefore provide better insight into the DNA radiation chemistry and aid in establishing reliable sugar dosimetry protocols. The first step in acquiring such knowledge is identification of the radical structures. Electron Magnetic Resonance (EMR) experiments on irradiated sugar single crystals allow a very detailed characterisation of the radicals via the g-tensor and the hyperfine interactions between the unpaired electron spin and the nuclear spins in the lattice. Single crystals also offer the advantage of mimicking to some extent the compact structure of chromosomal DNA. Numerous EMR studies on single crystals of sugars and sugar derivatives have been performed the last decades, but radical identification by EMR experiments alone is often ambiguous and sometimes not feasible. The last few years, highly accurate Density Functional Theory (DFT) calculations on extended organic solid state systems have become possible. These provide a powerful tool to help clarify and interpret experimental results and enable unambiguous structural identifications that were not possible before. In this talk, an overview will be given of recently identified radiation-induced radicals in single crystals of sugars (e.g. sucrose,1,2,3 fructose4) and sugar derivatives (e.g. glucose 1-phosphate5,6). The results pertain to primary as well as intermediate and stable species and the identifications are mainly based on the agreement, both in principal values and directions, between experimentally determined and DFT calculated proton hyperfine tensors. Common structural features are highlighted and possible commonly operative formation mechanisms are discussed

Modeling Radiation-Damage Processes in Organic Solids via DFT Calculations of EMR Parameters

High-energy radiation induces radicals in organic materials. When created in biological macromolecules such as DNA, these can cause harm to living organisms. This detrimental effect is also exploited for the sterilisation of e.g. foodstuffs, and radiation-induced radicals are used for dosimetry purposes. Knowledge of the structure of the radicals and their formation mechanisms is therefore of fundamental importance. In particular, radiation-induced radicals in solid sugars are studied (i) as model systems to gain insight into the precise role of the deoxyribose unit in the radiation chemistry of DNA and (ii) because of their potential as (emergency) dosimeters. X-irradiation typically gives rise to a variety of primary radicals in these systems, which then transform into stable radicals or diamagnetic species via one or more radical reactions. A prerequisite for unraveling the formation mechanisms is the identification of the different intermediate (semistable) radicals. Experimentally, solid-state sugar radicals can be characterised in detail by electron magnetic resonance (EMR) experiments. These allow determination of EMR parameters which describe the interaction of the unpaired-electron spin with its lattice environment, e.g. with (nearby) nuclear spins. Theoretical calculations of EMR parameters with DFT codes are increasingly being used to help clarify, interpret and explain experimental results. Recently we have managed, in a combined experimental and theoretical approach, to identify the structure of the major radiation-induced stable radicals in solid sucrose [1,2,3] (see Figure). We currently are investigating their formation mechanism, also via both EMR experiments and DFT modeling. A summary of the results obtained so far are presented

Combined Electron Magnetic Resonance and Density Functional Theory Study of Thermally Induced Free Radical Reactions in Fructose and Trehalose Single Crystals

Both as models for studying the effects of radiation on the DNA sugar unit and for applications in dosimetry, radiation-induced defects in sugars have in the past few decades been intensively studied with electron magnetic resonance (EMR) techniques, often with considerable success. However, irradiation generally gives rise to a large variety of free radicals, resulting in strongly composite Electron Paramagnetic Resonance (EPR) spectra. This complexity makes studying them quite a challenge. Despite considerable efforts, little is still known about the identity of the radicals and even less about the radical formation and transformation processes and mechanisms. At room temperature (RT) the primary radiation products, which may be stabilized upon low temperature (LT) irradiation, transform into stable radicals via multistep reaction mechanisms. While the species formed at LT are expected to be formed by simple processes, the molecular structure and geometry of the stable radicals may differ considerably from that of the intact molecule even in the solid state (crystals). Studying the intermediate radicals in the reactions occurring after LT irradiation helps elucidating the formation and identity of the stable radicals. The structural identification of these radicals is in most cases the result of a combination of EPR, Electron Nuclear Double Resonance (ENDOR) and ENDOR Induced EPR (EIE) experiments and advanced quantum chemistry calculations based on Density Functional Theory (DFT). In the present study a summary is given of the experimental EMR results obtained so far on radiation-induced radicals at different temperatures in fructose and trehalose single crystals and powders. “In situ” X-irradiation at LT (10 K) without annealing, leads to spectra strongly different from those observed after RT irradiation and offers the possibility to study and characterize the primary radiation products [1]. Performing EMR measurements on samples irradiated and/or annealed at various temperatures between LT (10 K or 77 K) and RT allows us to study the intermediate products, and such studies therefore have the potential to devise mechanistic links between the primary radicals and the stable radicals. In the present work, our own measurements are compared with results reported in the EMR literature. An outline at future experimental (EMR) and theoretical (DFT) research will also be given