Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms.

The review presents a detailed discussion of the evolving field studying interactions between ionic liquids (ILs) and biological systems. Originating from molten salt electrolytes to present multiapplication substances, ILs have found usage across various fields due to their exceptional physicochemical properties, including excellent tunability. However, their interactions with biological systems and potential influence on living organisms remain largely unexplored. This review examines the cytotoxic effects of ILs on cell cultures, biomolecules, and vertebrate and invertebrate organisms. Our understanding of IL toxicity, while growing in recent years, is yet nascent. The established findings include correlations between harmful effects of ILs and their ability to disturb cellular membranes, their potential to trigger oxidative stress in cells, and their ability to cause cell death via apoptosis. Future research directions proposed in the review include studying the distribution of various ILs within cellular compartments and organelles, investigating metabolic transformations of ILs in cells and organisms, detailed analysis of IL effects on proteins involved in oxidative stress and apoptosis, correlation studies between IL doses, exposure times and resulting adverse effects, and examination of effects of subtoxic concentrations of ILs on various biological objects. This review aims to serve as a critical analysis of the current body of knowledge on IL-related toxicity mechanisms. Furthermore, it can guide researchers toward the design of less toxic ILs and the informed use of ILs in drug development and medicine.

Fast evaluation of the safety of chemical reactions using cytotoxicity potentials and bio-Strips.

We introduce new quantitative environmental metrics - "cytotoxicity potentials" - which can be used for the preliminary evaluation of the safety of chemical reactions from the viewpoint of the cytotoxicity of their components. We also elaborate the concept of bio-Profiles to be employed for fast estimation of the potential environmental dangers of chemical processes by (1) including the common cytotoxicity scale for all routes of synthesis of a particular product and (2) proposing a novel, more compact representation of the bio-Profiles themselves in the form of bio-Strips. These improvements allow direct comparisons of various synthetic routes for a particular target product, thus providing faster assessment of the reactions in question from the viewpoint of their "overall cytotoxicity". The advantages of these developments are illustrated by 36 routes of synthesizing 1,1'-biphenyl and 72 routes of synthesizing 4-methoxy-1,1'-biphenyl. The effect of incomplete conversion on bio-Strips and their metrics is also discussed. In addition, we address the impact of the selection of a particular cell line on the evaluation of the reaction safety by comparing the results obtained in three cell lines of various origins.

Ionic liquids: prospects for nucleic acid handling and delivery.

Operations with nucleic acids are among the main means of studying the mechanisms of gene function and developing novel methods of molecular medicine and gene therapy. These endeavours usually imply the necessity of nucleic acid storage and delivery into eukaryotic cells. In spite of diversity of the existing dedicated techniques, all of them have their limitations. Thus, a recent notion of using ionic liquids in manipulations of nucleic acids has been attracting significant attention lately. Due to their unique physicochemical properties, in particular, their micro-structuring impact and tunability, ionic liquids are currently applied as solvents and stabilizing media in chemical synthesis, electrochemistry, biotechnology, and other areas. Here, we review the current knowledge on interactions between nucleic acids and ionic liquids and discuss potential advantages of applying the latter in delivery of the former into eukaryotic cells.

Evaluation of phytotoxicity and cytotoxicity of industrial catalyst components (Fe, Cu, Ni, Rh and Pd): A case of lethal toxicity of a rhodium salt in terrestrial plants.

Until recently, chemical derivatives of platinum group metals have not been in a systematic direct contact with living organisms. The situation has changed dramatically due to anthropogenic activity, which has led to significant redistribution of these metals in the biosphere. Millions of modern cars are equipped with automotive catalytic converters, which contain rhodium, palladium and platinum as active elements. Everyday usage of catalytic technologies promotes the propagation of catalyst components in the environment. Nevertheless, we still have not accumulated profound information on possible ecotoxic effects of these metal pollutants. In this study, we report a case of an extraordinarily rapid development of lethal toxicity of a rhodium (III) salt in the terrestrial plants Pisum sativum, Lupinus angustifolius and Cucumis sativus. The growth stage, at which the exposure occurred, had a crucial impact on the toxicity manifestation: at earlier stages, RhCl3 killed the plants within 24 h. In contrast, the salt was relatively low-toxic in human fibroblasts. We also address phytotoxicity of other common metal pollutants, such as palladium, iron, nickel and copper, together with their cytotoxicity. None of the tested compounds exhibited phytotoxic effects comparable with that of RhCl3. These results evidence the crucial deficiency in our knowledge on environmental dangers of newly widespread metal pollutants.

Investigation of Cytotoxic Activity of Mitoxantrone at the Individual Cell Level by Using Ionic-Liquid-Tag-Enhanced Mass Spectrometry.

A novel mitoxantrone conjugate was synthesized by coupling mitoxantrone with ionic liquid tags, and cytotoxic behavior of the designed conjugate was studied in normal and cancer cell lines. The synthesized mitoxantrone conjugate was oil at physiological temperatures and demonstrated high aqueous solubility. Sensitivity of electrospray ionization mass spectrometry (ESI-MS) to the mitoxantrone conjugate was improved by an order of magnitude, in comparison with original mitoxantrone dihydrochloride. The observed ESI-MS signals were shifted to a "clearer" lower-mass region of the spectrum, which allowed investigation of the drug at the level of individual cells. The ionic liquid tags proposed in the present work consist of an easily available imidazolium salt residue and show a number of key advantages from the points of view of drug conjugate synthesis, drug delivery and analytic detection.

Facile Chemical Access to Biologically Active Norcantharidin Derivatives from Biomass.

Reductive amination of 2,5-diformylfuran (DFF) was used to implement the transition from bio-derived 5-hydroxymethylfurfural (HMF) to pharmaceuticals. The synthesized bis(aminomethyl)furans were utilized as building blocks for the construction of new derivatives with structural cores of naturally occurring biologically active compounds. Using the one-pot procedure, which included the Diels-Alder reaction followed by hydrogenation of the double bond, bio-derived analogues of the anticancer drug norcantharidin were obtained. The cyclization process was diastereoselective, and resulted in the formation of tricyclic products with the endo configuration. Analysis of cytotoxycity for the resulting tricyclic amine-containing compounds showed an increase of anticancer activity as compared with the unsubstituted norcantharimide.

Cytotoxic Activity of Salicylic Acid-Containing Drug Models with Ionic and Covalent Binding.

Three different types of drug delivery platforms based on imidazolium ionic liquids (ILs) were synthesized in high preparative yields, namely, the models involving (i) ionic binding of drug and IL; (ii) covalent binding of drug and IL; and (iii) dual binding using both ionic and covalent approaches. Seven ionic liquids containing salicylic acid (SA-ILs) in the cation or/and in the anion were prepared, and their cytotoxicity toward the human cell lines CaCo-2 (colorectal adenocarcinoma) and 3215 LS (normal fibroblasts) was evaluated. Cytotoxicity of SA-ILs was significantly higher than that of conventional imidazolium-based ILs and was comparable to the pure salicylic acid. It is important to note that the obtained SA-ILs dissolved in water more readily than salicylic acid, suggesting benefits of possible usage of traditional nonsoluble active pharmaceutical ingredients in an ionic liquid form.