Strain in Silica-Supported Ga(III) Sites: Neither Too Much nor Too Little for Propane Dehydrogenation Catalytic Activity.

Well-defined Ga(III) sites on SiO2 are highly active, selective, and stable catalysts in the propane dehydrogenation (PDH) reaction. In this contribution, we evaluate the catalytic activity toward PDH of tricoordinated and tetracoordinated Ga(III) sites on SiO2 by means of first-principles calculations using realistic amorphous periodic SiO2 models. We evaluated the three reaction steps in PDH, namely, the C-H activation of propane to form propyl, the ß-hydride (ß-H) transfer to form propene and a gallium hydride, and the H-H coupling to release H2, regenerating the initial Ga-O bond and closing the catalytic cycle. Our work shows how Brønsted-Evans-Polanyi relationships are followed to a certain extent for these three reaction steps on Ga(III) sites on SiO2 and highlights the role of the strain of the reactive Ga-O pairs on such sites of realistic amorphous SiO2 models. It also shows how transition-state scaling holds very well for the ß-H transfer step. While highly strained sites are very reactive sites for the initial C-H activation, they are more difficult to regenerate. The corresponding less strained sites are not reactive enough, pointing to the need for the right balance in strain to be an effective site for PDH. Overall, our work provides an understanding of the intrinsic activity of acidic Ga single sites toward the PDH reaction and paves the way toward the design and prediction of better single-site catalysts on SiO2 for the PDH reaction.

Exploratory chemometric analysis of the classification of pharmaceutical substances based on chromatographic data.

A chemometric study has been conducted on a published data set consisting of the retention times of 83 substances, from five pharmacological families, on eight HPLC systems. Principal component analysis, clustering and sequential projection pursuit were applied. In this way it was investigated to what extent the combination of chromatography and chemometrics allows one to make conclusions about pharmacological activities of (candidate) drugs and what the contribution is of the different HPLC systems considered.

Use of mass spectrometry for assessing similarity/diversity of natural products with unknown chemical structures.

An evaluation whether mass spectral data contain useful information for assessing similarity/diversity of drug compounds is presented. A comparative study was carried out between Ward's hierarchical agglomerative clustering, based on the 2D Daylight fingerprints or on the mass spectra, of a small database of 66 synthetic substances. The influence of normalization of the mass spectral data on the clustering result has also been studied. The results were subsequently compared with an expert's classification of the same small dataset, based on own evaluation according to known structure and pharmacological activity.

[3D QSAR analysis of novel 5-HT1A receptor ligands]. / A szerotonin 5-HT1A receptorokhoz kötódó vegyületek három dimenziós mennyiségi szerkezet-hatás összefüggéseinek vizsgálata.

In an effort to develop a quantitative ligand-binding model for 5-HT1A receptors, a pharmacophore mapping procedure, DIStance COmparison (DISCO) was used to identify structural features that are common in a novel set of pyridazinothiazepines and pyridazinooxazepines with moderate-to high affinity to 5-HT1A-receptors. The pharmacophore thus obtained provided a good starting point for a Comparative Molecular Field Analysis (CoMFA) study. The CoMFA gave acceptable statistical measure (R2CV = 0.52 by using six latent variables, whereas it afforded a non cross-validated R2 value of 1.00). Predictability of our model was tested by a separated prediction set of four compounds, for them the relative deviations between calculated and measured biological activity values did not exceed 10%.

[Three dimensional structure-activity relationships]. / Három dimenziós szerkezet-hatás összefüggések.

Among the indirect drug design approaches, the 3D QSAR methods have been of great importance. They now belong to the most attractive and effective modelling tools of modern drug research. In this review, three major topics will be covered. The first focuses on the conformational analysis, in the second part the DIstance COmparison (DISCO) strategy will be discussed, and in the last part the philosophy of the Comparative Molecular Field Analysis (CoMFA) will be briefly described and illustrated.