Probing ionic liquid toxicity through biophysical and computational methods

Ionic liquids (ILs) have emerged as a promising class of materials due to their unique physicochemical and solvation properties. As a result of their ionic nature, ILs have been labeled "green" as these materials could potentially replace more harmful compounds, especially organic solvents. However, the past decade has revealed that ILs have a diverse toxicity profile and thus the "green" moniker may be misleading or even inaccurate, especially as certain ILs have been found to be exceptionally toxic to mammalian and aquatic species. Most studies involving IL toxicity measure the LC50 and adjacent parameters on one or more organisms. While these studies have been instrumental in revealing the harmful nature of ILs, they often do not uncover the mechanism behind the toxicity. More recently, biophysical and molecular dynamic (MD) methods have been employed to probe IL toxicity. These studies typically involve analyzing the interactions of ILs with lipid bilayers, as ILs mainly induce toxicity by manipulating the plasma membrane. These strategies have provided important discoveries and insights that allow for the design of more environmentally-benign ILs. This review provides a comprehensive description and analysis of the biophysical and MD techniques that are currently being used to understand IL toxicity as it relates to their impact on lipid bilayers, and in some cases, cells. Specific studies are described that showcase and exemplify each technique, and the review concludes with a perspective on the remaining challenges in the field of IL toxicity.