|Conţinutul numărului revistei|
|Ultima descărcare din IBN:|
| SM ISO690:2012|
GORINCIOI, Natalia; OGURŢOV, Ivan; TIHONOVSCHI, Andrei; BALAN, Igor; BERSUKER, Isaac; MARENICH, A; BOGGS, J. Toxicophores and quantitative structure – toxicity relationships for some environmental pollutants. In: Chemistry Journal of Moldova. 2008, nr. 1(3), pp. 94-104. ISSN 1857-1727.
|Chemistry Journal of Moldova|
|Numărul 1(3) / 2008 / ISSN 1857-1727 /ISSNe 2345-1688|
The electron-conformational (EC) method is employed to reveal the toxicophore and to predict aquatic toxicity quantitatively using as a training set a series of 51 compounds that have aquatic toxicity to ﬁsh. By performing conformational analysis (optimization of geometries of the low-energy conformers by the PM3 method) and electronic structure calculations (by ab initio method corrected within the SM54/PM3 solvatation model), the Electron-Conformational Matrix of Congruity (ECMC) was constructed for each conformation of these compounds. The toxicophore deﬁ ned as the EC sub-matrix of activity (ECSA), a sub-matrix with matrix elements common to all the active compounds under consideration within minimal tolerances, is determined by an iterative procedure of comparison of their ECMC’s, gradually minimizing the tolerances. Starting with only the four most toxic compounds, their ECSA (toxicophore) was found to consists of a 4x4 matrix (four sites with certain electronic and topologic characteristics) which was shown to be present in 17 most active compounds. A structure-toxicity
correlation between three toxicophore parameters and the activities of these 17 compounds with R2=0.94 was found. It is shown that the same toxicophore with larger tolerances satisﬁes the compounds with les activity, thus explicitly demonstrating how the activity is controlled by the tolerances quantitatively and which atoms (sites) are most ﬂexible in this respect. This allows for getting slightly different toxicophores for different levels of activity. For some active compounds that have no toxicophore a bimolecular mechanism of activity is suggested. Distinguished from other QSAR methods, no arbitrary descriptors and no statistics are involved in this EC structure-activity investigation.
aquatic toxicity, Electron-conformational method, QSAR