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

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• 作者：Sundaram Arulmozhiraja and Masatoshi Morita
• 刊名：Chemical Research in Toxicology
• 出版年：2004
• 出版时间：March 2004
• 年：2004
• 卷：17
• 期：3
• 页码：348 - 356
• 全文大小：127K
• 年卷期：v.17,no.3(March 2004)
• ISSN：1520-5010

文摘

The applicability of various density functional theory (DFT)-based descriptors-chemicalsoftness, electronegativity, and electrophilicity index-for quantitative structure-activityrelationships (QSARs) was investigated for polychlorinated dibenzofurans (PCDFs). The DFTdescriptors 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 inductionpotencies of PCDFs with DFT descriptors, hydrophobicity, and steric parameters. These QSARsexplain around 75% of variation in AhR binding affinities of PCDFs. Congeners with highertoxicity values had larger softness values. Studies also showed that the most toxic isomer oftetrachlorodibenzofurans (TCDFs) and dibenzo-p-dioxins (TCDDs), respectively, had the largestchemical softness value in its respective group. The results show that DFT descriptors couldbe 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.