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

Noise in Electron Devices

Contains reports on one research project.Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DA 36-039-AMC-03200(E

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

Direct-effect radiation chemistry of solid-state carbohydrates using EMR and DFT

To contribute to a mechanistic understanding of radical reaction pathways in the sugar-phosphate backbone of DNA, we are investigating primary radicals induced by X-rays, as well as their transformation into stable radicals or diamagnetic products, in crystalline sugar and sugar derivatives. Radicals are identified and characterized mainly via the hyperfine interactions of the electron spin with protons in the molecular environment. These interactions are determined experimentally with electron magnetic resonance (EMR) techniques and compared to theoretical ab initio calculations based on density functional theory in a periodic approach. Different stages of the radiation-induced processes are investigated by irradiating in situ at various temperatures and controlled annealing experiments. Here, results obtained in single crystals of the dipotassium salt of glucose 1-phosphate (K2G1P) and the disaccharides sucrose and trehalose are presented. The dominant radical in K2G1P after irradiation at 77 K exhibits a broken phospho-ester bond and is chemically identical to one of the major stable sucrose radicals, the latter all being characterized by a broken glycosidic bond. This suggests that the ester bond is radiation sensitive and that the phosphate group is not essential for the reaction pathway leading to this scission. Surprisingly, however, no evidence for glycosidic bond scission has so far been observed in trehalose. Rather, a simple H-abstraction alkyl radical is remarkably stable in this system. In all three compounds, dominant radicals are formed with one or several concerted carbonyl group formations. Extended studies are necessary to establish how and to which extent structural or geometrical factors determine the radiation chemistry, but certain general principles are starting to emerge

Successful Treatment of Early Endometrial Carcinoma by Local Delivery of Levonorgestrel: A Case Report

We describe a case of a 67-year-old Caucasian woman with an early, moderately-differentiated adenocarcinoma of the endometrium. A levonorgestrel-releasing intrauterine system was inserted, which she tolerated well. A full D&C, following removal of the device, was performed after 9 months, confirming absence of tumoral tissue. Examination after 24 months showed a very thin endometrium, indicating complete remission

Noise in Electron Devices

Contains reports on three research projects.Joint Services Electronics Program (Contract DA36-039-AMC-03200(E)