Membrane interactions of ionic liquids: Possible determinants for biological activity and toxicity

Ionic liquids (Its) are a class of diverse organic salts with relatively low melting points (below 100 degrees C) which have attracted considerable interest as a promising green substitute for organic solvents. The broad solvation properties of Its and their high solubility in water, however, present health risks, in particular since it was shown that many Its exhibit cytotoxic properties. In this context, interactions of Its with the cellular membrane are believed to constitute a primary culprit for toxicity. We present a comprehensive biophysical and microscopy study of membrane interactions of a series of Its having different side-chain compositions and lengths, and cationic head-group structures and orientations. The experimental data reveal that the Its studied exhibit distinct mechanisms of membrane binding, insertion, and disruption which could be correlated with their biological activities. The results indicate, in particular, that both the side chain composition and particularly the head-groups of Its constitute determinants for membrane activity and consequent cell toxicity. This work suggests that tuning membrane interactions of Its should be an important factor for designing future compounds with benign environmental impact. (C) 2012 Elsevier B.V. All rights reserved.