Room temperature ionic liquids (RTILs) and biomolecules are both paradigmatic classes of organic molecules, each consisting of a prodigious number of distinct chemical species, organized into large families of homologous compounds. Their combination is set to open new avenues for discoveries and for applications in biochemistry, biomedicine and pharmacology, food science, and nanotechnology. We provide a survey of past and current investigations of the chemical physics properties of systems made of RTILs and biomolecules, focusing on the most microscopic scales of their structure and dynamics. The primary goal of our discussion is to identify the basic principles able to organize and rationalize the vast variety of properties and phenomena displayed by these systems. We consider in turn RTILs combinations with phospholipids, with proteins and peptides, with nucleic acids (mainly DNA) and with carbohydrates from simple sugars to large polysaccharides. These basic components have a clear electrostatic signature, and Coulomb interactions represent the first ordering principle. However, because of size and complexity of both RTILs and biomolecules, dispersion interactions, steric effects, and hydrogen bonding play a secondary but certainly non-negligible role that is reflected in the sensitive dependence of RTIL/biomolecule properties on the RTIL choice. Our overview of the available results highlights both the need and the difficulty of devising general approaches able to predict properties of at least extended families of RTIL/biomolecules combinations, without having to consider them one by one in turn.

Ionic liquids (ILs) are a relatively new class of organic electrolytes composed of an organic cation and either an organic or inorganic anion, whose melting temperature falls around room-temperature. In the last 20 years, the toxicity of ILs towards cells and micro-organisms has been heavily investigated with the main aim to assess the risks associated with their potential use in (industrial) applications, and to develop strategies to design greener ILs. Toxicity, however, is synonym with affinity, and this has stimulated, in turn, a series of biophysical and chemical-physical investigations as well as few biochemical studies focused on the mechanisms of action (MoAs) of ILs, key step in the development of applications in bio-nanomedicine and bio-nanotechnology. This review has the intent to present an overview of the state of the art of the MoAs of ILs, which have been the focus of a limited number of studies but still sufficient enough to provide a first glimpse on the subject. The overall picture that emerges is quite intriguing and shows that ILs interact with cells in a variety of different mechanisms, including alteration of lipid distribution and cell membrane viscoelasticity, disruption of cell and nuclear membranes, mitochondrial permeabilization and dysfunction, generation of reactive oxygen species, chloroplast damage (in plants), alteration of transmembrane and cytoplasmatic proteins/enzyme functions, alteration of signaling pathways, and DNA fragmentation. Together with our earlier review work on the biophysics and chemical-physics of IL-cell membrane interactions (Biophys. Rev. 9:309, 2017), we hope that the present review, focused instead on the biochemical aspects, will stimulate a series of new investigations and discoveries in the still new and interdisciplinary field of “ILs, biomolecules, and cells.”

Empirical evidence and conceptual elaboration reveal and rationalise the remarkable affinity of organic ionic liquids for biomembranes. Cations of the so-called room-temperature ionic liquids (RTILs), in particular, are readily absorbed into the lipid fraction of biomembranes, causing a variety of observable biological effects, including generic cytotoxicity, broad anti-bacterial potential, and anti-cancer activity. Chemical-physics analysis of model systems made of phospholipid bilayers, RTIL ions and water confirm and partly explain this evidence, quantifying the mild destabilising effect of RTILs on structural, dynamical and thermodynamic properties of lipids in biomembranes. Our Feature Article presents a brief introduction to these systems and to their role in biophysics and in biotechnology, summarising recent experimental and computational results on their properties. More importantly, it highlights the many developments in pharmacology, bio-medicine and bio-nano technology expected from the current research effort on this topic. To anticipate future developments we speculate on: (i) potential applications of (magnetic) RTILs to affect and control the rheology of cells and biological tissues, of great relevance for diagnostics; and on: (ii) the usage of RTILs to improve the durability, reliability and output of bio-mimetic photovoltaic devices.