Ionic liquids are remarkable chemical compounds, which find applications in many areas of modern science. Because of their highly tunable nature and exceptional properties, ionic liquids have become essential players in the fields of synthesis and catalysis, extraction, electrochemistry, analytics, biotechnology, etc. Apart from physical and chemical features of ionic liquids, their high biological activity has been attracting significant attention from biochemists, ecologists, and medical scientists. This Review is dedicated to biological activities of ionic liquids, with a special emphasis on their potential employment in pharmaceutics and medicine. The accumulated data on the biological activity of ionic liquids, including their antimicrobial and cytotoxic properties, are discussed in view of possible applications in drug synthesis and drug delivery systems. Dedicated attention is given to a novel active pharmaceutical ingredient-ionic liquid (API-IL) concept, which suggests using traditional drugs in the form of ionic liquid species. The main aim of this Review is to attract a broad audience of chemical, biological, and medical scientists to study advantages of ionic liquid pharmaceutics. Overall, the discussed data highlight the importance of the research direction defined as "Ioliomics", studies of ions in liquids in modern chemistry, biology, and medicine.
Organometallic reagents and metal catalysts are used ubiquitously in academia and industry. Not surprisingly, the biological activity and environmental danger of metal compounds have become topics of outstanding importance. In spite of the rapid development of toxicology during the last decades, several common historically established “beliefs” are still frequently circulating in the organometallic community. In this Tutorial, we discuss existing opinions concerning (1) possibilities of toxicity measurements, (2) high toxicities of heavy-metal compounds, (3) correlation between the structure of a metal compound and its toxicity, (4) biological effect of direct/indirect contacts with metal compounds, and (5) dangers of metal nanoparticles. Basic concepts of toxicity studies and known data are described in the Tutorial step by step upon discussion of these issues. The main goal of this Tutorial is to demonstrate that the toxicity of a metal cannot be regarded as a constant property, since it depends on the oxidation state, ligands, solubility, morphology of particles, properties of the environment, and several other factors. As far as such chemically labile species as metal compounds are concerned, the nature of biological effects should not be assumed or taken for granted; indeed, reliable conclusions cannot be made without dedicated measurements.
Environmental profiles for the selected metals were compiled on the basis of available data on their biological activities. Analysis of the profiles suggests that the concept of toxic heavy metals and safe nontoxic alternatives based on lighter metals should be re-evaluated. Comparison of the toxicological data indicates that palladium, platinum, and gold compounds, often considered heavy and toxic, may in fact be not so dangerous, whereas complexes of nickel and copper, typically assumed to be green and sustainable alternatives, may possess significant toxicities, which is also greatly affected by the solubility in water and biological fluids. It appears that the development of new catalysts and novel applications should not rely on the existing assumptions concerning toxicity/nontoxicity. Overall, the available experimental data seem insufficient for accurate evaluation of biological activity of these metals and its modulation by the ligands. Without dedicated experimental measurements for particular metal/ligand frameworks, toxicity should not be used as a "selling point" when describing new catalysts.
Rapid progress in the field of ionic liquids in recent decades led to the development of many outstanding energy-conversion processes, catalytic systems, synthetic procedures, and important practical applications. Task-specific optimization emerged as a sharpening stone for the fine-tuning of structure of ionic liquids, which resulted in unprecedented efficiency at the molecular level. Ionic-liquid systems showed promising opportunities in the development of green and sustainable technologies; however, the chemical nature of ionic liquids is not intrinsically green. Many ionic liquids were found to be toxic or even highly toxic towards cells and living organisms. In this Review, we show that biological activity and cytotoxicity of ionic liquids dramatically depend on the nature of a biological system. An ionic liquid may be not toxic for particular cells or organisms, but may demonstrate high toxicity towards another target present in the environment. Thus, a careful selection of biological activity data is a must for the correct assessment of chemical technologies involving ionic liquids. In addition to the direct biological activity (immediate response), several indirect effects and aftereffects are of primary importance. The following principal factors were revealed to modulate toxicity of ionic liquids: i) length of an alkyl chain in the cation; ii) degree of functionalization in the side chain of the cation; iii) anion nature; iv) cation nature; and v) mutual influence of anion and cation.
Inorganic and organic "solvent-in-salt" (SIS) systems have been known for decades but have attracted significant attention only recently. Molten salt hydrates/solvates have been successfully employed as non-flammable, benign electrolytes in rechargeable lithium-ion batteries leading to a revolution in battery development and design. SIS with organic components (for example, ionic liquids containing small amounts of water) demonstrate remarkable thermal stability and tunability, and present a class of admittedly safer electrolytes, in comparison with traditional organic solvents. Water molecules tend to form nano- and microstructures (droplets and channel networks) in ionic media impacting their heterogeneity. Such microscale domains can be employed as microreactors for chemical and enzymatic synthesis. In this review, we address known SIS systems and discuss their composition, structure, properties and dynamics. Special attention is paid to the current and potential applications of inorganic and organic SIS systems in energy research, chemistry and biochemistry. A separate section of this review is dedicated to experimental methods of SIS investigation, which is crucial for the development of this field.
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