A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles

Jay Forrest; Paul Bazylewski; Robert Bauer; Seongjin Hong; Chang Yong Kim; John P. Giesy; Jong Seong Khim; Gap Soo Chang

doi:10.3389/fmars.2014.00031

A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles

Jay Forrest
, Paul Bazylewski
, Robert Bauer
, Seongjin Hong
, Chang Yong Kim
, John P. Giesy
, Jong Seong Khim
, Gap Soo Chang

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

15 Citations (Scopus)

2 Downloads (CityUHK Scholars)

Abstract

Here, we present a novel model to predict the toxicity and bioavailability of polychlorinated biphenyls (PCBs) as model compounds based on a first principles approach targeting basic electronic characteristics. The predictive model is based on an initio density functional theory. The model suggests HOMO-LUMO energy gap as the overarching indicator of PCBs toxicity, which was shown to be the primary factor predicting toxicity, but not the only factor. The model clearly explains why chlorination of both para positions is required for maximum toxic potency. To rank toxic potency, the "dipole moment" in relation to the most chemically active Cl-sites was critical. This finding was consistent with the accepted toxic equivalency factor (TEF) model for these molecules, and was also able to improve on ranking toxic potency of PCBs with similar TEFs. Predictions of HOMO-LUMO gap made with the model were consistent with measured values determined by synchrotron based X-ray spectroscopy for a subset of PCBs. HOMO-LUMO gap can also be used to predict bioaccumulation of PCBs. Overall, the new model provides an in silico method to screen a wide range of chemicals to predict their toxicity and bioavailability to act as an AhR agonist. © 2014 Forrest, Bazylewski, Bauer, Hong, Kim, Giesy, Khim and Chang.

Original language	English
Article number	31
Journal	Frontiers in Marine Science
Volume	1
Issue number	AUG
DOIs	https://doi.org/10.3389/fmars.2014.00031
Publication status	Published - 2014

Bibliographical note

Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

Funding

We gratefully acknowledge support from the Natural Sciences and Engineering Research Council of Canada (NSERC) and Canada Foundation for Innovation. Research described in this paper was performed at the Canadian Light Source, which is supported by NSERC, the National Research Council Canada, the Canadian Institutes of Health Research, the Province of Saskatchewan, Western Economic Diversification Canada, and the University of Saskatchewan. This work was also supported by the project entitled “Development of Technology for CO2 Marine Geological Storage” and “Oil Spill Environmental Impact Assessment and Environmental Restoration” funded by the Korean Ministry of Land, Transport, and Maritime Affairs given to Prof. Jong Seong Khim. Prof. John P. Giesy was supported by the Canada Research Chair program, a Visiting Distinguished Professorship in the Department of Biology and Chemistry and State Key Laboratory in Marine Pollution, City University of Hong Kong. He was also supported by the program of 2012 “High Level Foreign Experts” (#GDW20123200120) funded by the State Administration of Foreign Experts Affairs, P.R. China to Nanjing University and the Einstein Professor Program of the Chinese Academy of Sciences.

Research Keywords

Bioaccumulation
Dioxin-like PCBs
Dipole moment
HOMO-LUMO
Toxicity

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abstract = "Here, we present a novel model to predict the toxicity and bioavailability of polychlorinated biphenyls (PCBs) as model compounds based on a first principles approach targeting basic electronic characteristics. The predictive model is based on an initio density functional theory. The model suggests HOMO-LUMO energy gap as the overarching indicator of PCBs toxicity, which was shown to be the primary factor predicting toxicity, but not the only factor. The model clearly explains why chlorination of both para positions is required for maximum toxic potency. To rank toxic potency, the {"}dipole moment{"} in relation to the most chemically active Cl-sites was critical. This finding was consistent with the accepted toxic equivalency factor (TEF) model for these molecules, and was also able to improve on ranking toxic potency of PCBs with similar TEFs. Predictions of HOMO-LUMO gap made with the model were consistent with measured values determined by synchrotron based X-ray spectroscopy for a subset of PCBs. HOMO-LUMO gap can also be used to predict bioaccumulation of PCBs. Overall, the new model provides an in silico method to screen a wide range of chemicals to predict their toxicity and bioavailability to act as an AhR agonist. {\textcopyright} 2014 Forrest, Bazylewski, Bauer, Hong, Kim, Giesy, Khim and Chang.",

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AB - Here, we present a novel model to predict the toxicity and bioavailability of polychlorinated biphenyls (PCBs) as model compounds based on a first principles approach targeting basic electronic characteristics. The predictive model is based on an initio density functional theory. The model suggests HOMO-LUMO energy gap as the overarching indicator of PCBs toxicity, which was shown to be the primary factor predicting toxicity, but not the only factor. The model clearly explains why chlorination of both para positions is required for maximum toxic potency. To rank toxic potency, the "dipole moment" in relation to the most chemically active Cl-sites was critical. This finding was consistent with the accepted toxic equivalency factor (TEF) model for these molecules, and was also able to improve on ranking toxic potency of PCBs with similar TEFs. Predictions of HOMO-LUMO gap made with the model were consistent with measured values determined by synchrotron based X-ray spectroscopy for a subset of PCBs. HOMO-LUMO gap can also be used to predict bioaccumulation of PCBs. Overall, the new model provides an in silico method to screen a wide range of chemicals to predict their toxicity and bioavailability to act as an AhR agonist. © 2014 Forrest, Bazylewski, Bauer, Hong, Kim, Giesy, Khim and Chang.

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A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles

Abstract

Bibliographical note

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Research Keywords

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