QSAR model of the phototoxicity of polycyclic aromatic hydrocarbons

Abstract A Quantitative Structure–Activity Relationship (QSAR) study of 67 polycyclic aromatic hydrocarbons (PAHs) is performed and a prediction rule for the phototoxicity of these compounds is proposed. The geometry of all PAHs was optimized by semi-empirical method and used to calculate the following electronic descriptors: the highest occupied molecular orbital energy ( E HOMO ), the lowest unoccupied molecular orbital energy ( E LUMO ) and the GAP ( E HOMO − E LUMO ) between them. The relationships between these molecular descriptors and the photo-induced toxicity are non-linear, and Gaussian type functions were used to linearize them. The data set was autoscaled and partial least squares (PLS) with leave-one-out cross-validation was used for building the regression model. After the model was validated, the phototoxicity was predicted for a set of molecules in which experimental measurements are unknown. Pentaphene, benzo[b]chrysene and dibenz[a.j]anthracene are among the compounds potentially phototoxic as predicted by the model. A new GAP range (7.2±0.7 eV) is proposed for the classification of phototoxic compounds, and a larger cutoff suggested for the normalized lethal time as log(1/ALT)≤−2.95.

[1]  G. Ankley,et al.  Effects of light intensity on the phototoxicity of fluoranthene to a benthic macroinvertebrate. , 1995, Environmental science & technology.

[2]  G. Jori,et al.  Sunlight-activated insecticides: historical background and mechanisms of phototoxic activity. , 2000, Insect biochemistry and molecular biology.

[3]  David S. Page,et al.  A principal‐component and least‐squares method for allocating polycyclic aromatic hydrocarbons in sediment to multiple sources , 1997 .

[4]  G. Veith,et al.  QSAR Evaluation of .alpha.-Terthienyl Phototoxicity. , 1995, Environmental science & technology.

[5]  G. Veith,et al.  QSARs for photoinduced toxicity: I. Acute lethality of polycyclic aromatic hydrocarbons to Daphnia magna , 1994 .

[6]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[7]  W. A. Burns,et al.  Study of the Fates and Effects of the Exxon Valdez Oil Spill on Benthic Sediments in Two Bays in Prince William Sound, Alaska. 1. Study Design, Chemistry, and Source Fingerprinting , 1998 .

[8]  P. Geladi.  Notes on the history and nature of partial least squares (PLS) modelling , 1988 .

[9]  G. A. Burton,et al.  Photo-induced toxicity of PAHs to Hyalella azteca and Chironomus tentans: effects of mixtures and behavior. , 1999, Environmental pollution.

[10]  Ana Elisa,et al.  AVALIAÇÃO DA CONTAMINAÇÃO HUMANA POR HIDROCARBONETOS POLICÍCLICOS AROMÁTICOS (HPAS) E SEUS DERIVADOS NITRADOS (NHPAS): UMA REVISÃO METODOLÓGICA , 2000 .

[11]  Miss A.O. Penney.  (b) , 1974, The New Yale Book of Quotations.

[12]  D. Dixon,et al.  Pathway of anthracene modification under simulated solar radiation. , 2000, Chemosphere.

[13]  M. McBride.  Environmental Chemistry of Soils , 1994 .

[14]  I. Tolosa,et al.  Aliphatic and Polycyclic Aromatic Hydrocarbons and Sulfur/Oxygen Derivatives in Northwestern Mediterranean Sediments: Spatial and Temporal Variability, Fluxes, and Budgets , 1996 .

[15]  Márcia M. C. Ferreira,et al.  QSPR models of boiling point, octanol–water partition coefficient and retention time index of polycyclic aromatic hydrocarbons , 2003 .

[16]  Eamonn F. Healy,et al.  Development and use of quantum mechanical molecular models. 76. AM1: a new general purpose quantum mechanical molecular model , 1985 .

[17]  Márcia M. C. Ferreira,et al.  Polycyclic aromatic hydrocarbons: a QSPR study. Quantitative structure-property relationships. , 2001, Chemosphere.

[18]  Robert G. Parr,et al.  New measures of aromaticity: absolute hardness and relative hardness , 1989 .

[19]  J. W. Flesher,et al.  BENZYLIC CARBONIUM IONS AS ULTIMATE CARCINOGENS OF POLYNUCLEAR AROMATIC HYDROCARBONS , 1996 .

[20]  D. Crosby,et al.  Phototoxicity in tropical reef animals , 1996 .

[21]  J. Giesy,et al.  Predictive models for photoinduced acute toxicity of polycyclic aromatic hydrocarbons to Daphnia magna, strauss (cladocera, crustacea) , 1987 .

[22]  D Mackay,et al.  Mass balance model of source apportionment, transport and fate of PAHs in Lac Saint Louis, Quebec. , 2000, Chemosphere.

[23]  B. Kowalski,et al.  Partial least-squares regression: a tutorial , 1986 .

[24]  R. Parr,et al.  Absolute hardness as a measure of aromaticity , 1988 .

[25]  C. Davis,et al.  Phytophotodermatitis: the other "lime" disease. , 1999, The Journal of emergency medicine.