QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP (QSAR). V. ANALYSIS OF THE TOXICITY OF ALIPHATIC ESTERS BY MEANS
OF MOLECULAR COMPRESSIBILITY DESCRIPTORS.
VICENŢIU VLAIA^1* TUDOR OLARIU¹, LAVINIA VLAIA²,
MARIUS BUTUR³, CIPRIAN CIUBOTARIU⁴, MIHAI MEDELEANU⁵,
DAN CIUBOTARIU¹
University of Medicine and Pharmacy “Victor Babeş”, Faculty of Pharmacy
1Department of Organic Chemistry,
2Department of Pharmaceutical Technology,
3Department of Mathematics and Biostatistics,
4Technical University “Politehnica” Timisoara, Department of Computer
Sciences
5Technical University “Politehnica” Timisoara, Department of Organic
Chemistry
*corresponding author: vlaiav@yahoo.com


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Abstract:

The present work represents an attempt to correlate toxicity of aliphatic esters using calculated molecular descriptors based on properties of the molecular van der Waals (vdW) space considered compressible in some extent. Assuming that a molecule can be compressed from the greatest sphere, corresponding to the vdW surface S^w , to the smallest sphere, corresponding to the vdW volume,V^w , we developed three i-dimensional structural parameters C_iD, i=1,2,3, which are measures of compressibility in iD molecular vdW space.
C_iD compressibility measures of the vdW molecular space were tested with good results on a series of 56 aliphatic esters exhibiting toxicity to ciliate protozoan Tetrahymena pyriformis. A reduced series of 49 esters was obtained by outlier statistical analysis. The quality and the robustness of all the QSAR models were analyzed. For the QSAR model wherein C_2D was used as predictor variable, the external cross-validation was performed. The goodness of fit and the predictive power of the QSAR models developed in this study show that accurately describing the toxicity of aliphatic esters with a single correlation equation is quite feasible if the physical meaning of the molecular descriptors is clear.

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