Richard A. O'Brien

The Fluid-Mosaic Model, Homeoviscous Adaptation, and Ionic Liquids: Dramatic Lowering of the Melting Point by Side-Chain Unsaturation†

Proposed by Singer and Nicolson in 1972, the fluid-mosaic model holds that the phospholipid bilayer is a dynamic twodimensional solvent milieu. Its proper function is closely tied to its “fluidity”, and that is often quantified by reference to the melting point, Tm (increased fluidity corresponds to a lower Tm value). The fluid-mosaic model is highly evocative of the emerging picture of nanoscale structuring in ionic liquids (ILs), and just as the function of phospholipid bilayers is tied to the Tm value, so too is the utility of ILs. Whereas the former often have low Tm values despite being composed of charged species with long aliphatic appendages, the fluidity of ILs generally decreases when progressively longer aliphatic appendages are used. It is a challenge to design imidazolium ILs (the most common IL class) that incorporate progressively more lipophilic structural elements while keeping their melting points below room temperature (Figure 1). Indeed, the Tm values of these ILs begin to rise dramatically once an appended Nalkyl group exceeds seven carbon atoms in length. Herein we report that by using an approach modeled on homeoviscous adaptation (HVA), ILs with very long alkyl appendages and very low Tm values can be prepared. This discovery may have significant implications for IL use in enzymatic catalysis, lubricants, heat-transfer fluids, and gas storage and separation, among other applications. Widely accepted as a mechanism by which the melting temperature of cell membranes is modulated, HVA is the incorporation into cell membranes of phospholipids with “kinked” tail structures. It is argued that the packing efficiency of the collective membrane hydrophobic components is diminished by the presence of these phospholipids and that increased fluidity results. A comparison of the Tm value of distearoylphosphatidylcholine with that of dioleylphosphatidylcholine provides a dramatic example of how much impact this seemingly trivial difference can have. The former, with its linear, saturated C18 tails has a Tm value of 58 8C; the latter, with its “kinked” C18 tails (each of which incorporates a cis-alkenyl group), has a Tm value of 22 8C. This effect is also at the heart of the Tm difference between the solid triacyl glycerols called fats, and those that are liquid at room temperature known as oils. In both instances, the effect is probably entropic in nature, as in the case of anthracene (“linear”, Tm = 217 8C) and phenanthrene (“kinked”, Tm = 99 8C). Accordingly, we hypothesized that ILs with long, unsaturated, aliphatic tail structures would, like the corresponding phospholipids, have significantly lower Tm values than their counterparts with saturated appendages. To test the validity of our hypothesis by measuring their Tm values, we prepared a series of lipid-inspired ILs in a threestep process from high-purity (99 + %) fatty-alcohol mesylates, 1-methylimidazole, NaI, and NaTf2N. [12] Each of the ILs (Scheme 1) had a long alkyl appendage identical to that in a natural fatty acid. Compounds 1, 3, and 8 feature fully saturated C16, C18, and C20 side chains, respectively, and their Figure 1. Influence of alkyl-chain length on Tm in N-alkyl N-methylimidazolium salts and the corresponding n-alkanes. The graph includes data from the literature and newly synthesized ionic liquids.

On the Formation of a Protic Ionic Liquid in Nature

The practical utility of ionic liquids (ILs) makes the absence (heretofore) of reported examples from nature quite puzzling, given the facility with which nature produces many other types of exotic but utilitarian substances. In that vein, we report here the identification and characterization of a naturally occurring protic IL. It can be formed during confrontations between the ants S. invicta and N. fulva. After being sprayed with alkaloid-based S. invicta venom, N. fulva detoxifies by grooming with its own venom, formic acid. The mixture is a viscous liquid manifestly different from either of the constituents. Further, we find that the change results as a consequence of formic acid protonation of the N centers of the S. invicta venom alkaloids. The resulting mixed-cation ammonium formate milieu has properties consistent with its classification as a protic IL.

A simple and rapid route to novel tetra(4-thiaalkyl)ammonium bromides

A simple approach for the preparation of symmetrical quaternary ammonium bromides employing thiol–ene click chemistry is used to synthesize tetra(4-thiaalkyl)ammonium bromides. This approach allows the incorporation of a variety of alkyl moieties onto the nitrogen center with a one-step synthesis involving easy work-up, no side reactions and environmentally friendly reagents. To elucidate information regarding the behaviour of this novel class of compounds, comparisons to tetraalkylammonium analogues have been made. These include melting points, activity as phase-transfer catalysts, and conformational predictions from computational modelling. All results are consistent in indicating stronger bonding between the quaternary cation and the anion for the salts with 4-thiaalkyl chains as compared to those with n-alkyl chains.

Thermally robust: triarylsulfonium ionic liquids stable in air for 90 days at 300 °C

Select triarylsulfonium salts constitute ionic liquids with outstanding long-term, high-temperature aerobic stability (no mass loss in 90 days at 300 °C in air), making them among the most thermally stable organic materials known. A detailed analysis of their thermophysical properties reveals that lowering melting points in these salts by increasing ion size or lowering ion symmetry cannot be assumed, but remains an iterative process.

Thioether-functionalized picolinium ionic liquids: synthesis, physical properties and computational studies

A series of ionic liquids containing 3- and 4-picolinium cations appended to thioether side chain moieties was constructed via the thiol–ene “click” reaction. Their structure–property relationships were comprehensively investigated by studying the temperature transition region (melting points and glass transition temperatures) and heat capacity and the experimental results were fully supported by theoretical studies. The synthesized ionic liquids are melted below 20.2 °C. Also, the impact of varying chain length, type of cations (picolinium vs. imidazolium) and the position of methyl group on the ring on their thermal and thermophysical properties were explored. According to the collected data, the glass transition temperature values of the picolinium-based ionic liquids with odd-number chains is lower than the even-number ones, which shows that the even-number moieties have more organized structures. And the miscibility of selected ionic liquids in water (polar) and heptane (nonpolar) solvents were quantified.

Click chemistry mediated synthesis of bio-inspired phosphonyl-functionalized ionic liquids†

This study focuses on the synthesis of a class of novel biologically-inspired ionic liquids coupled with a phosphonate group containing short to long side chains (C3–C11) via the Pudovic reaction. The ionic liquids exhibited very low glass transition temperatures and were hydrophobic in character. This method has the attributes of “click” chemistry with outstanding efficiency, simplicity, yields and regioselectivity. The results of their calcium(II) ligating capability are also presented.

Chapter 6 – Synthesis and Properties of Lipid-Inspired Ionic Liquids

Lipid-inspired ionic liquids are a novel class of biomaterials that utilize structural features similar to natural lipids to allow the incorporation of the lipophilic structural elements while maintaining their melting points below room temperature. In this chapter, we will primarily focus on the synthesis and thermophysical properties of new generations of lipid-inspired ionic liquids.

Biomimetic design of protic lipidic ionic liquids with enhanced fluidity

We demonstrate herein a facile synthesis of a series of highly-ordered low-melting protic ionic liquids with linear C16–C20 side chains identical to natural fatty acids, which were produced by the S-alkylation of the 2-mercapto-1-methylimidazole (methimazole) ring. There is considerable structural latitude possible when designing highly lipophilic protic ionic liquids that exhibit low Tm values due to the cumulative disruptive effects of thioether and unsaturation on their packing efficiency. Their bulk thermophysical properties, hydrophobicity and cytotoxicity were also determined.

Crystal structure of a methimazole-based ionic liquid.

The structure of 1-methyl-2-(prop-2-en-1-ylsulfanyl)-1H-imidazol-3-ium bromide, C7H11N2S+·Br−, has monoclinic (P21/c) symmetry. In the crystal, the components are linked by N—H⋯Br and C—H⋯Br hydrogen bonds. The crystal structure of the title compound undeniably proves that methimazole reacts through the thione tautomer, rather than the thiol tautomer in this system.