Structure−Activity Relationships for the Toxicity of Polychlorinated Dibenzofurans:  Approach through Density Functional Theory-Based Descriptors

• Published in: Chemical research in toxicology Vol. 17; no. 3; pp. 348 - 356
• Main Authors: Arulmozhiraja, Sundaram, Morita, Masatoshi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.03.2004
• Subjects: Air Pollutants, Occupational - chemistry; Air Pollutants, Occupational - toxicity; Aryl Hydrocarbon Hydroxylases - metabolism; Benzofurans - chemistry; Benzofurans - toxicity; Binding Sites; Cytochrome P-450 CYP1A1; Dibenzofurans, Polychlorinated; Hydrophobic and Hydrophilic Interactions; Models, Molecular; Quantitative Structure-Activity Relationship; Receptors, Aryl Hydrocarbon - metabolism
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx0300380

The applicability of various density functional theory (DFT)-based descriptorschemical softness, electronegativity, and electrophilicity indexfor quantitative structure−activity relationships (QSARs) was investigated for polychlorinated dibenzofurans (PCDFs). The DFT descriptors were obtained by using the three parameter hybrid density functional, B3LYP, with the 6-311G(d,p) basis set. QSARs were developed relating aryl hydrocarbon receptor (AhR) binding affinities, aryl hydrocarbon hydroxylase and ethoxyresorufin O-deethylase induction potencies of PCDFs with DFT descriptors, hydrophobicity, and steric parameters. These QSARs explain around 75% of variation in AhR binding affinities of PCDFs. Congeners with higher toxicity values had larger softness values. Studies also showed that the most toxic isomer of tetrachlorodibenzofurans (TCDFs) and dibenzo-p-dioxins (TCDDs), respectively, had the largest chemical softness value in its respective group. The results show that DFT descriptors could be used as useful electronic descriptors in QSARs for the prediction of toxicity of PCDFs. Overall, 85 congeners of PCDFs and TCDDs were considered in this study.