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.

The amenability of different schemes for the calculation of atomic charges in the electronegativity equalization method (EEM) is investigated. To that end, a large training set of molecules was composed, comprising H, C, N, O, and F, covering a wide range of medicinal chemistry. Geometries are calculated at the B3LYP/6-31G* level. Atomic charges are calculated using five different methods, belonging to different types of population analysis. Effective electronegativities and hardness values are calibrated from the different quantum chemically calculated atomic charges. The resulting quality of EEM charges is investigated for the different types of atomic charge calculation methods. EEM-derived Mulliken and NPA charges are in good agreement with the ab initio values, electrostatic potential derived, and Hirshfeld charges show no good agreement.

Performance on the Verbal Fluency Test, as a measure of the ability of initiating processes, is reduced in depressed suicidal patients. The hampered results in this prefrontal executive task parallel the reduction in prefrontal blood perfusion and metabolism in depressed subjects. A neuropsychological activation study with the verbal fluency paradigm could evaluate a possible blunted increase in perfusion in the prefrontal cortex in depressed suicidal patients. Twenty clinically depressed patients who had recently attempted suicide and 20 healthy volunteers were included in a single photon emission computed tomography (SPECT) split-dose activation study following a verbal fluency paradigm. Statistical parametric mapping was used to determine voxelwise significant changes. Differences in regional cortical activation between the letter fluency and category fluency tasks in attempted suicide patients were found. These patients showed a blunted increase in perfusion in the prefrontal cortex. Methodological restrictions concerning group uniformity, medication bias and subjective effort of the participants are discussed. Our findings indicate a blunted increase in prefrontal blood perfusion as a possible biological reason for reduced drive and loss of initiative in attempted suicide patients.

Positron emission tomography (PET) was used to observe changes in regional cerebral blood flow (rCBF) in 10 right-handed healthy volunteers performing two paradigms of mental rotation. In one paradigm, subjects mentally rotated a single alphanumeric stimulus to determine whether it was shown in a normal or mirror-image position. In a second paradigm, subjects mentally rotated and compared pairs of figurative stimuli to determine whether the stimuli were identical or mirror-images. In both paradigms, rCBF was compared with a control task that used identical stimuli, but required no mental rotation. Mental rotation of single alphanumeric stimuli engendered activation in the primary somatomotor area in the left precentral gyrus. Mental rotation of paired figures engendered activation in the left superior parietal lobule and the right frontal medial gyrus. A deactivated area was located in the medial part of the left superior frontal gyrus. Comparison of both paradigms revealed that the left gyrus precentralis was activated significantly during the alphanumeric condition and that the left gyrus lingualis was significantly activated during the paired figures condition. Motor processes may be an inherent part of every mental rotation but the type of motor involvement appears strongly dependent on the specific task or the specific stimuli. Similar paradigms, designed to isolate the same cognitive function, in the same subjects, using the same imaging technology and methodology, but differing only in stimulus material, lead to different areas of neural activation. Task specificity determines the most significant changes in cerebral blood flow in different mental rotation paradigms.

We present the results of density functional calculations of 1 H, 13 C, and 14 N hyperfine coupling constants (hfcc's) in radicals derived from the simple amino acid L-alanine. The calculations are performed using the B3LYP functional in combination with Pople basis sets (6-31G(d) and 6-311G(d)) and the IGLO-III basis set. Both isotropic and anisotropic hfcc's show good agreement with available experimental data. Detailed study of the isotropic hfcc's allows for investigation of specific geometrical features of the various radical structures. The scope and limitations of this type of calculations both for elucidation of experimental electron paramagnetic resonance spectra and investigation of radical structure are briefly discussed.

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.

This study aimed to investigate the feasibility of brain single-photon emission tomography (SPET) in the letter and category fluency paradigm of the Controlled Oral Word Association (COWA) test in healthy volunteers. Two groups each comprising ten right-handed healthy volunteers were injected twice with 370 MBq technetium-99m ethyl cysteinate dimer following a split-dose paradigm (resting and activation condition). Statistical parametric mapping (SPM96) was used to determine voxelwise significant changes. The letter fluency and the category fluency activation paradigm had a differential brain activation pattern. The posterior part of the left inferior prefrontal cortex (LIPC) was activated in both paradigms, with the category fluency task having an extra activation in the anterior LIPC. In the category fluency task, but not the letter fluency task, an activation in the right inferior prefrontal cortex was found. These findings confirm to a large extent the results of previous functional magnetic resonance imaging and positron emission tomography studies in semantic and phonological activation paradigms. The choice and validity of various methodological characteristics of the experimental design leading to these results are critically discussed. It is concluded that brain SPET activation with the letter fluency and category fluency paradigm under standard neuropsychological conditions in healthy volunteers is both technically and practically feasible.

No abstract