Daily Archives: November 12, 2014

Quantitative Structure-Activity and Fluoride Toxicity

Hongchen D, Wang Y, Li Y, Xu Z, Wang S, Riye Ni. Quantitative structure–activity study of fluorides′ toxicity. Journal of Fluorine Chemistry. Volume 156, December 2013, Pages 30–33DOI: 10.1016/j.jfluchem.2013.08.011

The molecular geometries and electronic structures of 14 fluorides are optimized using density functional theory (DFT) B3LYP/6-31G*, B3P86/6-31G* and Møller–Plesset perturbation theory MP2/6-31G* methods. E  HOMO, E  LUMO, ΔE  , μ  , Q  F, Q  M and V   are chosen as the structural descriptors. The acute toxicity (−lg LC  50) of fluorides to rats along with the above structural parameters are used to establish the quantitative structure–activity relationships (QSARs). The results show that the models based on the DFT-B3LYP/6-31G* is better than that based on B3P86/6-31G* and MP2/6-31G* methods. The toxic mechanism is controlled mainly by electronic factor Q  F (the maximum net atomic charge on fluorides). The QSAR relationship between the electronic parameters Q  F and the toxicity −lg LC  50 is: −lg LC  50 = 0.032 + 7.037Q  F (View the MathML source, SE = 0.37097, F = 27.578, P = 0.013). An overall cross-validation correlation coefficient is then obtained using leave-one-out method and the calculated cross-validation coefficient (q2) value is 0.660. The predicted toxic values using the above equation are in good agreement with the experimental values, and the QSAR model has good stability and strong prediction ability.