Comprehensive approach for predicting toxicological effects of ionic liquids on several biological systems using unified descriptors.

Chul-Woong Cho,Yeoung-Sang Yun,Stefan Stolte

doi:10.1038/srep33403

Chul-Woong Cho, Yeoung-Sang Yun + Show 1 more

Open Access

https://doi.org/10.1038/srep33403

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Abstract

The challenge and opportunity for design of environmentally-benign ionic liquids (ILs) would start from prediction of their toxicological effects on several endpoints solely based on the structural formulas. Especially, a comprehensive yet simple equation able to predict several biological responses to IL toxicity is of much advantage. Therefore, based on 50 toxicity testing systems on ILs a comprehensively approachable prediction method was developed. For the modelling, approximately 1600 toxicity values measured by several biological systems and an amended linear free energy relationship (LFER) model were used. Since the toxicological activities of an IL could be differently described according to sensitivity of toxicity testing systems, the sensitivity of each of toxicity testing systems was also estimated in the modelling. By statistical analysis with the calculated descriptors, a LFER model was built. Also the sensitivity value of each system on the basis of the comprehensively approachable model was numerically estimated. In results, it was observed that the combination of single model and sensitivity terms was able to predict each of 50 toxicological effects of ILs with R2 of 0.593~0.978, and SE of 0.098~0.699 log unit, and the total data set with R2 of 0.901 and SE of 0.426 log unit.

Highlights

Ionic liquids (ILs) as a molten salt around room temperature have been highlighted in chemical industries because of their excellent physicochemical properties[1]
In the viewpoint of finding relationships among biological responses, the concept of this research is slightly related to previous article[33], which presented that based on quantitative toxicity-toxicity relationship (QTTR), interspecies correlation between different biological responses to toxicants can be applied to predict non-existing toxicity data for a particular compound
To build the comprehensively approachable model based on various biological responses to IL toxicity, it was hypothesized that toxicity test methods have a similar response pattern and different sensitivities according to IL chemical structure and organism’s tolerance to toxicants

Summary

Explanation on theoretical model

Linear free energy relationship (LFER) concept was used because it consists of simple and well-defined solute descriptors (E, S, A, B, V, J−, J+)[37] and it has been used for predicting the toxicological effects of chemicals as previously shown[38]. The small letters (e, s, a, b, v, j−, j+, and c) are system parameters (sometimes, called as system coefficients) explaining the molecular interactions of toxicity testing system. They can be determined by multiple linear regression (MLR) analysis. The capital letters are solute descriptors that describe the intrinsic molecular interaction potentials of an atom or a molecule. The experimental values for LFER descriptors are not limited to all ions of ILs; they were calculated according to the methods developed by our group[39]

Results and Discussion

SE zx αx βx

Conclusions

Additional Information