P. Lahorte

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

F. De Proft, E. Pauwels, P. Lahorte, V. Van Speybroeck, M. Waroquier, P. Geerlings

Magnetic Resonance in Chemistry

42 (Sp. Iss. S1), S3-S19

2004

A1

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 β-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 β-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.

Open Access version available at UGent repository

DOI

http://dx.doi.org/10.1002/mrc.1444

Tentative Structures for the Radiation-Induced Radicals in Crystalline β-d-Fructose Using Density Functional Theory

E. Pauwels, P. Lahorte, G. Vanhaelewyn, F. Callens, F. De Proft, P. Geerlings, M. Waroquier

Journal of Physical Chemistry A

106 (51), 12370-12375

2002

A1

Abstract

In this study, density functional theory calculations were used to identify the structure of the radiation-induced radicals in solid state β-d-fructose, using a single molecule approach. Four model radicals were proposed, and the electron paramagnetic resonance (EPR) parameters were calculated for the optimized geometries. These calculated parameters were subsequently compared with those of two radical species, observed in an experimental EPR and electron nuclear double resonance study on irradiated fructose (Vanhaelewyn, G.; Lahorte, P.; De Proft, F.; Mondelaers, W.; Geerlings, P.; Callens, F. Phys. Chem. Chem. Phys. 2001, 3, 1729). On the basis of this preliminary comparison, three model structures were rejected. By varying the main degree of freedom of the remaining model, a number of conformations were obtained that yielded isotropic and anisotropic hyperfine tensor components in close agreement with experimental results. To disentangle between these possible conformers, a detailed study was made of the hyperfine tensor eigenvectors. One conformation was found to be in close agreement with the experimental measurement of the hyperfine tensor of the two observed radical species. It was concluded that these experimental species are in fact manifestations of one and the same radical, with a structure conforming to our model but with slightly altered conformations.

DOI

http://dx.doi.org/10.1021/jp0264174

The Electronegativity Equalization Method I: Parametrization and Validation for Atomic Charge Calculations

P. Bultinck, W. Langenaeker, P. Lahorte, F. De Proft, P. Geerlings, M. Waroquier, J.P. Tollenaere

Journal of Physical Chemistry A

106(34), 7887-7894

2002

A1

Abstract

The applicability of the electronegativity equalization method (EEM) is investigated for the fast calculation of atomic charges in organic chemistry, with an emphasis on medicinal chemistry. A large training set of molecules was composed, comprising H, C, N, O, and F, covering a wide range of medicinal chemistry. Geometries and atomic charges are calculated at the B3LYP/6-31G* level, and from the calculated charges, effective electronegativity and hardness values are calibrated in a weighted least-squares fashion. The optimized parameter set is compared to other theoretical as well as experimental values and origins of the differences discussed. An approach toward extension of EEM to include new atoms is introduced. The quality of the EEM charges is assessed by comparison with B3LYP/6-31G* charges calculated for a set of medicinal molecules, not contained in the training set. The EEM approach is found to be a very powerful way to obtain ab initio quality charges without the computational cost of the ab initio approach.

DOI

http://dx.doi.org/10.1021/jp0205463

Density Functional Calculations on Alanine-Derived Radicals: Influence of Molecular Environment on EPR Hyperfine Coupling Constants

E. Pauwels, V. Van Speybroeck, P. Lahorte, M. Waroquier

Journal of Physical Chemistry A

105 (38), 8794–8804

2001

A1

Abstract

The amino acid l-α-alanine and its associated radiation-induced radicals display particular characteristics in solid-state that make it very appropriate for use in Electron Paramagnetic Resonance (EPR) dosimetry. In contrast to the number of experimental studies, relatively few theoretical studies have been published concerning the EPR parameters of these radicals. However, these studies inadequately account for the molecular environment of the alanine radicals in the crystalline lattice. Here, we present Density Functional Theory (DFT) calculations on one of the stable radiation-induced radicals of l-α-alanine both in molecular cluster models and in periodic models. An extensive investigation is presented on the various geometrical ingredients which have a substantial impact on the hyperfine coupling constants as the planarity of the radical backbone and the internal rotations of the final methyl and amino group vary. It is found that the accurate modeling of the hydrogen bonds with neighboring molecules is of utmost importance for an adequate reproduction of the experimental data.