title: Exploring simple, transparent, interpretable and predictive QSAR models for classification and quantitative prediction of rat toxicity of ionic liquids using OECD recommended guidelines.
abstract: The present study explores the chemical attributes of diverse ionic liquids responsible for their cytotoxicity in a rat leukemia cell line (IPC-81) by developing predictive classification as well as regression-based mathematical models. Simple and interpretable descriptors derived from a two-dimensional representation of the chemical structures along with quantum topological molecular similarity indices have been used for model development, employing unambiguous modeling strategies that strictly obey the guidelines of the Organization for Economic Co-operation and Development (OECD) for quantitative structure-activity relationship (QSAR) analysis. The structure-toxicity relationships that emerged from both classification and regression-based models were in accordance with the findings of some previous studies. The models suggested that the cytotoxicity of ionic liquids is dependent on the cationic surfactant action, long alkyl side chains, cationic lipophilicity as well as aromaticity, the presence of a dialkylamino substituent at the 4-position of the pyridinium nucleus and a bulky anionic moiety. The models have been transparently presented in the form of equations, thus allowing their easy transferability in accordance with the OECD guidelines. The models have also been subjected to rigorous validation tests proving their predictive potential and can hence be used for designing novel and "greener" ionic liquids. The major strength of the present study lies in the use of a diverse and large dataset, use of simple reproducible descriptors and compliance with the OECD norms.
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: Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India; Manchester Institute of Biotechnology, 131 Princess Street, Manchester M1 7DN, United Kingdom. Electronic address: kunal.roy@manchester.ac.uk.
authors.forename: Kunal
authors.initials: K
authors.lastname: Roy
authors.affiliation: Manchester Institute of Biotechnology, 131 Princess Street, Manchester M1 7DN, United Kingdom. Electronic address: paul.popelier@manchester.ac.uk.
authors.forename: Paul L A
authors.initials: PL
authors.lastname: Popelier
mesh_terms: D000465:Algorithms; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016002:Discriminant Analysis; D017408:Guidelines as Topic; D052578:Ionic Liquids / Q000737:chemistry* / Q000633:toxicity*; D008962:Models, Theoretical; D066150:Organisation for Economic Co-Operation and Development; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D012044:Regression Analysis
chemical_list: D052578:Ionic Liquids
keywords: Cytotoxicity modeling; Discriminant analysis; Green solvent; Ionic liquids; Partial least squares; QSAR