title: Quantitative structure-activity relationship for toxicity of ionic liquids to Daphnia magna: aromaticity vs. lipophilicity.
abstract: 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.
authors.affiliation: 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. Electronic address: kunal.roy@manchester.ac.uk.
authors.forename: Kunal
authors.initials: K
authors.lastname: Roy
authors.affiliation: Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India.
authors.forename: Rudra Narayan
authors.initials: RN
authors.lastname: Das
authors.affiliation: Manchester Institute of Biotechnology, 131 Princess Street, Manchester M1 7DN, Great Britain, United Kingdom. Electronic address: paul.popelier@manchester.ac.uk.
authors.forename: Paul L A
authors.initials: PL
authors.lastname: Popelier
mesh_terms: D000818:Animals; D003621:Daphnia / Q000187:drug effects*; D055772:Green Chemistry Technology; D057927:Hydrophobic and Hydrophilic Interactions; D052578:Ionic Liquids / Q000737:chemistry* / Q000633:toxicity*; D016018:Least-Squares Analysis; D015233:Models, Statistical; D021281:Quantitative Structure-Activity Relationship; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D018675:Toxicity Tests
chemical_list: D052578:Ionic Liquids; D012997:Solvents
keywords: Aromaticity; ETA; Ionic liquid; Lipophilicity; QSAR; QTMS