A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles
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 suggest...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2014-08-01
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| Series: | Frontiers in Marine Science |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmars.2014.00031/full |
| _version_ | 1811235054977810432 |
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| author | Jay eForrest Paul eBazylewski Robert eBauer Seongjin eHong Chang Yong eKim John P Giesy Jong Seong eKhim Gap Soo eChang |
| author_facet | Jay eForrest Paul eBazylewski Robert eBauer Seongjin eHong Chang Yong eKim John P Giesy Jong Seong eKhim Gap Soo eChang |
| author_sort | Jay eForrest |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T11:45:42Z |
| format | Article |
| id | doaj.art-fbbb56af7b6149b5982a40c5df27829f |
| institution | Directory Open Access Journal |
| issn | 2296-7745 |
| language | English |
| last_indexed | 2024-04-12T11:45:42Z |
| publishDate | 2014-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Marine Science |
| spelling | doaj.art-fbbb56af7b6149b5982a40c5df27829f2022-12-22T03:34:22ZengFrontiers Media S.A.Frontiers in Marine Science2296-77452014-08-01110.3389/fmars.2014.00031104177A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principlesJay eForrest0Paul eBazylewski1Robert eBauer2Seongjin eHong3Chang Yong eKim4John P Giesy5Jong Seong eKhim6Gap Soo eChang7University of SaskatchewanUniversity of SaskatchewanUniversity of SaskatchewanSeoul National UniversityCanadian Light SourceUniversity of SaskatchewanSeoul National UniversityUniversity of SaskatchewanHere, 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.http://journal.frontiersin.org/Journal/10.3389/fmars.2014.00031/fullToxicitybioaccumulationdipole momentHOMO-LUMODioxin-like PCBs |
| spellingShingle | Jay eForrest Paul eBazylewski Robert eBauer Seongjin eHong Chang Yong eKim John P Giesy Jong Seong eKhim Gap Soo eChang A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles Frontiers in Marine Science Toxicity bioaccumulation dipole moment HOMO-LUMO Dioxin-like PCBs |
| title | A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles |
| title_full | A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles |
| title_fullStr | A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles |
| title_full_unstemmed | A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles |
| title_short | A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles |
| title_sort | comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles |
| topic | Toxicity bioaccumulation dipole moment HOMO-LUMO Dioxin-like PCBs |
| url | http://journal.frontiersin.org/Journal/10.3389/fmars.2014.00031/full |
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