A quantum chemical study on a set of non-imidazole H(3) antihistamine molecules

Molecular orbital calculations were carried out on a set of 28 non-imidazole H(3) antihistamine compounds using the Hartree-Fock method in order to investigate the possible relationships between electronic structural properties and binding affinity for H3 receptors (pK(i)). It was observed that the frontier effective-for-reaction molecular orbital (FERMO) energies were better correlated with pK(i) values than highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy values. Exploratory data analysis through hierarchical cluster (HCA) and principal component analysis (PCA) showed a separation of the compounds in two sets, one grouping the molecules with high pK(i) values, the other gathering low pK(i) value compounds. This separation was obtained with the use of the following descriptors: FERMO energies (epsilon(FERMO)), charges derived from the electrostatic potential on the nitrogen atom (N(1)), electronic density indexes for FERMO on the N(1) atom (Sigma((FERMO))c(i)(2)). and electrophilicity (omega`). These electronic descriptors were used to construct a quantitative structure-activity relationship (QSAR) model through the partial least-squares (PLS) method with three principal components. This model generated Q(2) = 0.88 and R(2) = 0.927 values obtained from a training set and external validation of 23 and 5 molecules, respectively. After the analysis of the PLS regression equation and the values for the selected electronic descriptors, it is suggested that high values of FERMO energies and of Sigma((FERMO))c(i)(2), together with low values of electrophilicity and pronounced negative charges on N(1) appear as desirable properties for the conception of new molecules which might have high binding affinity. 2010 Elsevier Inc. All rights reserved.

Inlärning och öppet-fält aktivitet hos förskolebarn

The purpose of this study was to analyze the impact of learning on open-field activity among pre-school children varying from 3 to 5 years old. Altogether 25 children, 13 girls and 12 boys, entered the test from three different preschools in Dalarna. Six of these children represented the control group. The children were asked to learn 2 tasks, 1 visual memory task and 1 spatial constructing-kit task. Before, between and after the tasks, the children were allowed to move freely in the open field. The control group did not solve any learning tasks and only entered the open field, which was divided into 18 equally large squares, where the children’s activities were observed. The children’s learning times as well as their spontaneous open-field activity and wall-seeking behaviour were registered. The result showed as a general rule that the learning time was reduced between each session. However, the visual memory task increased the children’s spontaneous open-field behaviour more and decreased their wall seeking to a greater extent than the spatial-construction learning task.