Computation of chromatographic lipophilicity parameter logk0 of ionic liquid cations from “ETA” descriptors: Application in modeling of toxicity of ionic liquids to pathogenic bacteria

Lipophilicity plays a determinant role for modeling toxicity, surfactancy, biological activity and other properties of chemicals. Considering the novel applications of ionic liquids (ILs) in a wide variety of chemical operations, understanding their lipophilicity seems useful. Due to the limited availability of experimental data on lipophilicity of ionic liquids, it will be of value to develop reliable predictive models for lipophilicity of ILs using computed chemical descriptors. Such models can be of help for the prediction of lipophilicity of untested/new ILs even before commencing their synthesis. Lipophilicity is a well researched and accepted major attribute for toxicological manifestations where bio-membrane partitioning represents the central mechanism, i.e., for non-specific toxicity. Considering the growing interest on assessment of hazardous potential of ILs aiming to design environmentally more benevolent analogs, a computed lipophilicity measure can aid in modeling various toxicity responses. In a previous study, we have reported predictive models on the chromatographic lipophilicity of ionic liquid cations using topological and quantum chemical descriptors. The primary objective of the present study involves refinement of the previous model avoiding the use of computationally more demanding quantum chemical features, and to develop a model from descriptors that can be determined from two-dimensional structural representation (extended topochemical atom (ETA) indices) consuming less computational resources and using an open source platform (PaDEL-Descriptor, http://www.yapcwsoft.com/dd/padeldescriptor/). Here, we have employed partial least square (PLS) regression for the development of robust models. The model was developed in consonance with the OECD principles of QSAR model development and, it portrayed the importance of cationic bulk due to long alkyl chain substituents and the presence of polar atoms (oxygen atom of -OH, − COOH, nitrogen atom of − CN etc.) on the cationic substituent in quantifying lipophilicity of ionic liquid cations. We have additionally modeled toxicity of a second set of ionic liquids towards four species of pathogenic bacteria using the computed lipophilicity values along with different ETA indices. Encouraging results were obtained showing the importance of computed lipophilicity measure, cationic molecular bulk and hydrogen bonding propensity of anions.