Manchester Institute of Biotechnology, 131 Princess Street, Manchester M1 7DN, Great Britain, United Kingdom; Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India.
Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India.
Chemosphere. 2014 Oct;112:120-7. doi: 10.1016/j.chemosphere.2014.04.002. Epub 2014 May 4.
Water solubility of ionic liquids (ILs) allows their dispersion into aquatic systems and raises concerns on their pollutant potential. Again, lipophilicity can contribute to the toxicity of ILs due to increased ability of the compounds to cross lipoidal bio-membranes. In the present work, we have performed statistical model development for toxicity of a set of ionic liquids to Daphnia magna, a widely accepted model organism for toxicity testing, using computed lipophilicity, atom-type fragment, quantum topological molecular similarity (QTMS) and extended topochemical atom (ETA) descriptors. The models have been developed and validated in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for quantitative structure-activity relationships (QSARs). The best partial least squares (PLS) model outperforms the previously reported multiple linear regression (MLR) model in statistical quality and predictive ability (R(2)=0.955, Q(2)=0.917, Rpred(2)=0.848). In this work, the ETA descriptors show importance of branching and aromaticity while the QTMS descriptor ellipticity efficiently shows which compounds are influential in the data set, with reference to the model. While obvious importance of lipophilicity is evident from the models, the best model clearly shows the importance of aromaticity suggesting that more lipophilic ILs with less toxicity may be designed by avoiding aromaticity, nitrogen atoms and increasing branching in the cationic structure. The developed quantitative models are in consonance with the recent hypothesis of importance of aromaticity for toxicity of ILs.
离子液体(ILs)的水溶性使其能够分散到水生系统中,并引起人们对其潜在污染的关注。同样,亲脂性也会由于化合物增加穿过类脂生物膜的能力而导致 ILs 的毒性增加。在本工作中,我们使用计算的亲脂性、原子类型片段、量子拓扑分子相似性(QTMS)和扩展拓扑原子(ETA)描述符,为一组离子液体对大型蚤(一种广泛用于毒性测试的模型生物)的毒性进行了统计模型开发。该模型是根据经济合作与发展组织(OECD)定量构效关系(QSAR)指南开发和验证的。最佳偏最小二乘(PLS)模型在统计质量和预测能力方面优于先前报道的多元线性回归(MLR)模型(R2=0.955,Q2=0.917,Rpred2=0.848)。在这项工作中,ETA 描述符显示了分支和芳香性的重要性,而 QTMS 描述符的椭圆率有效地显示了哪些化合物对数据集中的模型有影响。虽然模型明显表明亲脂性的重要性,但最佳模型清楚地表明芳香性的重要性,这表明通过避免芳香性、氮原子和增加阳离子结构中的分支,可以设计出毒性更小的更亲脂性的 ILs。所开发的定量模型与最近关于 ILs 毒性的芳香性重要性的假设是一致的。
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