Ribeiro F. A. L., Ferreira M. M. C., “QSAR MODEL OF THE PHOTOTOXICITY OF POLYCYCLIC AROMATIC HYDROCARBONS”. Caxambu, MG, Brazil, 11-16/11/2001: 1º Simpósio Brasileiro em Química Medicinal, QSAR e Modelagem Molecular: Novas Estratégias em Planejamento Racional de Fármacos [1st Brazilian Symposium on Medicinal Chemistry, QSAR and Molecular Modeling: New Approaches in Drug Design]. Poster APM11. Section: 4. Applications of Multivariate QSAR.
phototoxicity
Name
Fabiana Alves de Lima Ribeiro, Márcia M. C. Ferreira
Institution/Company
UNICAMP
Country
Brasil
First Abstract Title
QSAR MODEL OF THE PHOTOTOXICITY OF POLYCYCLIC AROMATIC HYDROCARBONS
First Abstract
Ribeiro, F. A. L.; Ferreira, M. M. C.; Laboratório de Quimiometria
Teórica e Aplicada, Instituto de Química
Universidade Estadual de Campinas, Campinas SP 13083-970.
The rising preoccupation about the discharge of
polyciclic aromatic hydrocarbons (PAHs) in the environment, has stimulated
the investigation of the properties and
biological activities of these chemicals, because they are well known to
be carcinogenic and toxic compounds. PAHs
are produced by degradation or incomplete combustion of organic materials,
like in the burning of wool and coal,
exhaust of gasoline and diesel combustion engines, the smoking of tobacco,
and other combustion processes in
which the carbon fuel is not completely converted to CO or CO2.(1) Recent
research has demonstrated that when
exposed to UV radiation, some PAHs can become extremely toxic, a phenomenon
known as phototoxicity. The UV
and visible radiation can be sufficiently energetic to modify the chemical
structure of some compounds generating
biologically active species. Upon the sunlight exposure, some PAHs can
undergo rapid structural modifications which
occurs by photooxidation reactions, and the products originated from these
modifications might present toxicity. This
toxicity is due to p-orbital system of PAHs, which strongly absorb sunlight
in the UV and visible light.(2) In this study,
a QSAR model is built with the aim to predict the phototoxicity of some
PAHs using the following electronic
descriptors: HOMO and LUMO energies, and the difference between them, named
as GAP. Firstly, the geometry of all
molecules were optimized and the frontier orbital energies and GAP were
calculated by the semi-empirical method
AM1 using Spartan software. These three electronic variables, selected
to construct the model, don't present
necessarily a linear correlation with the phototoxicity. Gaussian functions
were used to linearize these relationships
allowing the construction of a linear QSAR model. Experimental phototoxicity
for Daphnia magna of PAHs, expressed
as the median adjusted lethal time ALT, was taken from literature for a
set of 14 molecules.(3) The model was
constructed by partial least square method PLS, using autoscaled data and
leave-one-out crossvalidation. Pirouette
2.02 (Infometrix) and MATLAB (MathWorks Inc) software were used. Two latent
variables describing 91.1% of total
variance showed to be significant, producing a model with correlation coefficient
r = 0.967 and validation errors smaller
than 5% (with a few exceptions). Phototoxicity was predicted for a set
of 56 molecules in which experimental
measurements were not performed yet. benzo[h]pentaphene, naphto[2,3-g]chrysene
and coronene are predicted
among the most phototoxic compounds, whereas acenaphtylene and benzo[a]perylene
are not predicted to be.
ACKNOWLEDGEMENTS. The authors would like to thank Lucicleide R. Cirino
for her help in making calculations,
CAPES, FAPESP and FAEP for financial support, and CENAPAD for the computational
support. REFERENCES 1 -
BAIRD, C.; Environmental Chemistry, 2nd ed., W. H. Freeman and Company,
USA, 1995. 2 - SCHAEFFER, FAIC, D
J. & LARSON, R. A., The Chemist, July/August, 1999, 18-24. 3 - MEKENYAN,
O. G.; ANKLEY, G. T.; VEITH, G. D.;
CALL, D. J, Chemosfere, v. 28, n. 3, 1994, 567-582.