Detection of small differences in the hydrophilicity of ions using the LCST-type phase transition of an ionic liquid–water mixture

Abstract

The phase separation temperature of the tetrabutylphosphonium trifluoroacetate–water mixture, which undergoes a lower critical solution temperature-type phase transition, is highly sensitive to the hydrophilicity of added salts; this system can be used to compare the hydrophilicity of the added ions.

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Ionic liquids (ILs) consisting entirely of ions are increasingly proposed as alternatives to conventional organic solvents because of their unique combination of properties, such as negligible vapour pressure, less-flammability and ion diversity.^1–4 To attain desirable properties, recent studies of ILs have focused on mixed systems comprising other molecular solvents and ILs, rather than pure IL systems. In particular, IL–water mixtures are expected to be potential media for many biological and chemical processes.^5–8

In such applications, the hydrophilicity of component ions in IL–water mixtures is an important physico-chemical parameter. This is because the hydrophilicity of component ions strongly influences various fluid properties of the IL–water mixtures. Some hydrophilic ILs that contain small amounts of water, classified as hydrated ILs, are capable of dissolving proteins without significant damage to their higher-order structure.^9,10 In the interaction between an IL–water mixture and proteins, the hydrophilicity of ions is important in stabilising the higher-order structure of proteins.^11,12 Conversely, ILs with fluorinated anions such as hexafluorophosphate (PF₆⁻), and bis(trifluoromethane-sulfonyl)imide ([Tf₂N]) anions are hydrophobic, and generally provide stable liquid–liquid biphases after mixing with water.^13,14 These hydrophobic IL–water biphasic systems have been used as extraction media for various compounds including biomaterials.^15–18 Extraction using IL–water mixtures is governed by the hydrophilicity of the component ions.¹⁹ However no systematic method for comparing the hydrophilicity of component ions has yet been established.

We recently reported that a few ILs underwent a lower critical solution temperature (LCST)-type phase transition after mixing with water. In the LCST-type phase transition, the homogeneous mixture underwent phase separation upon heating, and the mixture became homogeneous again upon cooling.^20–23 The phase separation temperature (T_c) of LCST-type IL–water mixtures was found to increase with increasing hydrophilicity of the component ions. The T_c value of an LCST-type IL–water mixture changes by mixing a different kind of IL. This indicated that the LCST-type IL–water mixture could be suitable for evaluating the hydrophilicity of target ions by determining the T_c value after addition of salts containing the target ion species. This method would permit the detection of differences in the hydrophilicity of the target ions. The value of T_c is readily determined visually as the temperature at which the solution begins to become turbid upon heating. Below, we propose a novel system for comparing the hydrophilicity of target ions using an IL–water mixture that undergoes an LCST-type phase transition.

The structure of the ion species for which the hydrophilicity is to be compared is shown in Fig. 1. As a standard solution that exhibits the LCST-type phase transition, we chose tetrabutylphosphonium trifluoroacetate ([P₄₄₄₄]CF₃COO) mixed with an equal weight of water (50 wt%); this mixture undergoes phase separation at a moderate temperature (32 °C). To keep the system as simple as possible, we chose a series of added salts composed of several ion species but keeping either [P₄₄₄₄]⁺ or CF₃COO⁻ as counter ions. In that case there are only [P₄₄₄₄]⁺, CF₃COO⁻, and target ions after mixing the added salts. The value of T_c was determined visually during heating. The hydrophilicity of ions can be compared from the relation between T_c values and the concentration of the added salts.

Fig. 1 Structure of component ions used in comparing hydrophilicity.

Fig. 2 shows the T_c values of [P₄₄₄₄]CF₃COO–water mixtures after adding [P₄₄₄₄]⁺-based salts having different anion species. The value of T_c depends on both the ion species and the concentration of the added salts. When water soluble ILs, [P₄₄₄₄]CH₃SO₃, [P₄₄₄₄]Cl, [P₄₄₄₄]Br, [P₄₄₄₄]NO₃, and [P₄₄₄₄][TsO] were added to the mixture, the values of T_c were higher than that for the [P₄₄₄₄]CF₃COO–water mixture (50 wt%). When the specified salts were mixed at a concentration of 0.20 M, the T_c values were 50 °C, 47 °C, 39 °C, 34 °C, and 33 °C, respectively. Conversely, ILs with fluorinated anions such as [P₄₄₄₄]BF₄, [P₄₄₄₄]CF₃SO₃, and [P₄₄₄₄][Tf₂N] were immiscible with water, and lower values of T_c were observed than that for the [P₄₄₄₄]CF₃COO–water mixture (50 wt%). When the concentration of [P₄₄₄₄]BF₄ or [P₄₄₄₄]CF₃SO₃ was 0.20 M, the T_c values were 18 °C and 17 °C, respectively. Although [P₄₄₄₄][Tf₂N] did not dissolve in the mixture at a concentration above 0.10 M, the decrease in T_c relative to concentration was greater than that for any other salt. It is apparent that highly hydrophilic salts caused T_c to increase, and that less hydrophilic salts caused it to fall. The resulting order of hydrophilicity of the anions used in this study is as follows: CH₃SO₃⁻ > Cl⁻ > Br⁻ > [TsO]⁻ > NO₃⁻ > CF₃COO⁻ > BF₄⁻ > CF₃SO₃⁻ > [Tf₂N]⁻. Since the change in T_c from that of the [P₄₄₄₄]CF₃COO–water mixture (50 wt%) was greater when the concentration of added salts increased, it should be possible to detect small differences in the hydrophilicity of anions.

Fig. 2 Effect of added anion species on the phase separation temperature (T_c) of [P₄₄₄₄]CF₃COO–water mixtures. The black point (●) denotes the value of T_c for the mixture with no other salt.

Fig. 3 shows T_c values for the [P₄₄₄₄]CF₃COO–water mixture after mixing with CF₃COO⁻-based salts having different cation species. We chose [C4mim]CF₃COO, [C4pyr]CF₃COO, and [N₄₄₄₄]CF₃COO as water-miscible ILs. These have the same alkyl chain length, and so are useful for comparing the relation between structure and hydrophilicity of cation species. When these three water-miscible ILs were mixed into the standard solution, higher values of T_c were observed than that for the [P₄₄₄₄]CF₃COO–water mixture (50 wt%). When the concentration of [C4mim]CF₃COO, [C4pyr]CF₃COO, and [N₄₄₄₄]CF₃COO was 0.20 M, the T_c values were 41 °C, 40 °C, and 35 °C, respectively. Of the nitrogen containing cations, imidazolium and pyridinium have similar structure, but our observations suggest that the 1-butyl-3-methylimidazolium cation is more hydrophilic than the 1-butylpyridinium cation. On the other hand, [P₅₅₅₅]CF₃COO is chosen as a water-immiscible IL, and caused a fall in T_c from that of the [P₄₄₄₄]CF₃COO–water mixture (50 wt%). These observations imply the following order of hydrophilicity of the cations used in this study: [C4mim]⁺ > [C4pyr]⁺ > [N₄₄₄₄]⁺ > [P₄₄₄₄]⁺ > [P₅₅₅₅]⁺. These results indicate that the present LCST-type IL–water mixture is a simple system suitable for determining the order of hydrophilicity of ions by comparing the values of T_c of the IL–water mixture after adding the target ions.

Fig. 3 Effect of added cation species on the phase separation temperature (T_c) of [P₄₄₄₄]CF₃COO–water mixtures. The black point (●) denotes the value of T_c for the mixture with no other salt.

Although various types of ILs exist with differing hydrophilicity, only a few reports compare the degree of hydrophilicity of ions. The maximum water content in the separated IL phase is a key parameter of hydrophobic ILs in comparing the hydrophilicity of ions,^23–25 and we have estimated ion hydrophilicity from the maximum water content of hydrophobic ILs.²³ We determined the maximum water content of the separated IL phase of a series of hydrophobic ILs, all having the same counter ion. The maximum water content was greater for the IL phase in the IL–water mixture containing ions that were more hydrophilic. For IL–water mixtures that undergo the LCST-type phase transition, the maximum water content of the separated IL phase depends strongly on the temperature in comparison with the hydrophobic IL–water biphasic mixture, and increased significantly near T_c. We measured the maximum water content of the separated IL phases at 10 °C above T_c. The salts, used to depict Fig. 2 and 3, were added (0.20 M) to the [P₄₄₄₄]CF₃COO–water mixture to determine T_c. Fig. 4 shows the relation between T_c and the maximum water content of the separated IL phase at the temperature 10 °C higher than T_c. There was a clear relation between these parameters, and higher water content of the separated IL phase was found in the mixtures for which T_c was higher. It is considered that the salting out effect also influenced the maximum water content of the separated IL phase, especially in the case of hydrophilic salt addition. In general, this effect makes the maximum water content of the separated IL phase decreased. However the maximum water content of the separated IL phase increased with increasing hydrophilicity of the added salts. Considering these, the effect of salting out should be much smaller than that of the added salts on the maximum water content. These results strongly support the hypothesis that the change in the value of T_c is due to the hydrophilicity of the target ions.

Fig. 4 Relation between phase separation temperature (T_c) of the mixture and the maximum water content of the separated IL phase at the temperature 10 °C higher than T_c.

The T_c value changed linearly with increasing concentration of the added salts. Higher concentrations of the added salts changed the value of T_c considerably but sometimes made the measurements difficult; addition of hydrophobic salts lowered T_c below the freezing point of the water phase, for instance. On the other hand there was very little change in the T_c values of IL–water mixtures after mixing with a small amount of added salts. In the present study, we added 0.20 M salts to compare the hydrophilicity of the ions. However, it is necessary to fix the best concentration of other salts for comparison due to the above-mentioned reason.

Some hydrophobic salts, such as [P₄₄₄₄][Tf₂N], are almost insoluble in water, making it difficult to detect any change in the values of T_c. The solubility of hydrophobic salts can be increased by allowing the less hydrophilic system or by increasing the IL content of the system to undergo an LCST-type phase transition.

In conclusion we have developed a simple system for comparing the hydrophilicity of target ions by exploiting the temperature-sensitive LCST-type phase transition of IL–water mixtures. This system enables us to compare small differences in the hydrophilicity of ions. To determine T_c, the LCST-type phase transition was analysed visually. The LCST-type phase transition of IL–water mixtures makes it easy to study the properties of IL–water mixtures, including binary or multisystems.

This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant No. 21225007).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: The preparation method and purity of ionic liquids. See DOI: 10.1039/c2cc37006a

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