Density functional theory as a tool for the structure determination of radiation-induced bioradicals

Abstract

The use of density functional methods for the elucidation of the structure of radiation-induced bio-radicals by comparison of computed and experimental EPR properties is discussed. Three case studies, radiation induced radicals of the amino acid alanine, steroid hormones and b-D-fructose, with increasing degree of uncertainty about the proposed radical structures, are investigated. Next to the analysis of the isotropic and anisotropic components of the hyperfine tensor, also the direction cosines of the principal axes of this tensor were investigated in greater detail in the case of the b-D-fructose radicals. Since all radicals considered in this contribution are formed in a solid matrix, also the question as to how to incorporate the effect of the molecular environment is addressed. It is concluded that the methodology outlined represents a powerful tool to aid experimentalists in the assignment of the contributions of various radicals contributing to the observed EPR spectra. Copyright  2004 John Wiley & Sons, Ltd. KEYWORDS: EPR; density functional theory; bioradicals; radiation; structure; alanine; fructose INTRODUCTION PrologueIn this contribution, which is of a review type, electron paramagnetic resonance (EPR) properties are discussed as a source of information on the structure of radiation-induced bioradicals in the solid state. More precisely, we will show, via three case studies, how the comparison of the computed and experimental EPR properties of a series of radiationinduced radicals can be used to confirm or propose the structure of these radicals.A large number of the studies on amino acids (in particular alanine) and sugars are motivated by their potential dosimetric applications. L-˛-Alanine, for example, is currently used as a reference dosimeter suitable over a wide dose range.1 In the first part, the hyperfine coupling constants for various candidate alanine radicals are discussed.2 For this system, many studies are available yielding a substantial amount of structural information and EPR spectroscopic properties of irradiated solid L-˛-alanine. As a result, this system represents and ideal test case for the purpose of exploring and validating the DFT calculation of hfccs in † Dedicated to Professor M. Barfield on the occasion of his 70th birthday. Ł Correspondence to: F. De Proft, Eenheid Algemene Chemie (ALGC), Vrije Universiteit Brussel (VUB), Faculteit Wetenschappen, Pleinlaan 2, 1050 Brussels, Belgium. E-mail: fdeprof@vub.ac.be radiation-induced bioradicals for the purpose of structure elucidation. At the end of this section, we will briefly mention the results of a study on the EPR properties of steroid radicals, 3 where various experimental studies available agree on the identity of two different radicals whereas another two radicals form the subject of ongoing debate, to which the results of the theoretical analysis presented here can contribute significantly.In the final section, a theoretical study is discussed on the tentative structures of fructose radicals, 4 following an earlier ...

Q-Band EPR and ENDOR of Low Temperature X-Irradiated β-d-Fructose Single Crystals

“…Recent advances in the development of fast computers and efficient algorithms have offered computational groups the ability to calculate complex radical structures in shorter time. In that respect, density functional theory (DFT) has already in many cases proven to be quite adequate in reproducing experimental hyperfine coupling tensors and hence assisting in radical model assignments and structure determinations. , …”

“…In that respect, density functional theory (DFT) has already in many cases proven to be quite adequate in reproducing experimental hyperfine coupling tensors and hence assisting in radical model assignments and structure determinations. 1,2 A central issue in the radiation chemistry of DNA is the identity and the consequential effects of primary radicals in the 2′-deoxy-D-ribose sugar unit. Irradiation of DNA causes sugar radicals through, e.g., ionization followed by deprotonation at the carbon sites.…”

Investigation of the nitrogen hyperfine coupling of the second stable radical in γ-irradiated l-alanine crystals by 2D-HYSCORE spectroscopy

“…Thus, the cross-peak pattern does not contain information about the relative signs of A and Q. The chosen sign for the principal values of A was based on theoretical prediction [25,38,39,[42][43][44].…”

“…Although R2 is by far the simplest radical, formed by the abstraction of the aÀproton, and differs from undamaged alanine by only one hydrogen atom, as seen in Fig. 1 nitrogen HF interaction has only been extrapolated [25] and predicted by several theoretical investigations performed using different theoretical methods [36][37][38][39][40][41][42][43][44][45][46]. In Table 1, a summary of the calculated hyperfine coupling constants for the R2 radical as determined in various levels of theory is shown.…”