Control of LCST phase transition behaviour of phosphonium-based ionic liquids in water using supramolecular host–guest chemistry

Abstract

Some phosphonium-based ionic liquids exhibit LCST phase transition behaviour in water. This study demonstrates that host–guest interactions obtained by adding an α-cyclodextrin host increased their LCST phase transition temperature (T_LCST). NMR analysis confirmed the complex formation between the phosphonium cation and α-cyclodextrin that drives the drastic change of T_LCST.

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Design, System, Application

LCST phase transition behavior of ionic liquids in water has attracted attention for the development of dynamic functional materials in a variety of fields including energy and environmental sciences. Herein, supramolecular host–guest interaction has been successfully employed for controlling the LCST phase transition temperature. The LCST transition temperature of tetrabutyl phosphonium p-toluenesulfonate in water has been controlled by more than 20 °C just by the addition of 0.1 mol of α-cyclodextrin per tetrabutyl phosphonium cation. It is attributed to the formation of a supramolecular host–guest complex between the tetrabutyl phosphonium cation and α-cyclodextrin. The present design may lead to the development of new ideas for controlling the physicochemical properties of various functional ionic liquids.

Ionic liquids (ILs) are organic salts that exist in liquid states at ambient temperature.¹ ILs have attracted significant attention owing to their unique physicochemical properties such as flame retardancy and non-volatility along with high ion density and ionic conductivity.² One of the significant reasons that they have been studied in a wide area of research is that their physicochemical properties and functions can be widely modulated by designing their cations and anions.³

In 2007, our group found unique ILs showing LCST phase transition behaviour in water (Fig. 1a).⁴ For example, [P₄₄₄₄][Tf-leu] showed an LCST phase transition at 25 °C in water.⁴ A key design principle for such ILs involves combining suitable cations and anions with moderate hydrophobicity.⁵ Based on this approach, we have developed a range of ILs having LCST ability.⁵ The gelation and/or polymerization of polymerizable ILs with suitable hydrophobicity have also been investigated by our group⁶ and others.⁷ These phosphonium-based ILs and their derivatives, with or without LCST ability, have wide applications for drug delivery,⁸ selective extraction of proteins⁹ and biomaterials,¹⁰ and chemical/enzymatic catalysis.¹¹ Additionally, they are used as soft actuators,¹² cleaning agents for fouled membranes¹³ and stimuli-responsive photoluminescent materials.¹⁴ For the realization of these practical uses, one of the key points is the precise control of the LCST phase transition temperature. The control of the LCST phase transition temperature of these ILs has been achieved by modifying their cations and anions as well as employing a strategy to mix two ILs.¹⁵ The thermal behaviour of phosphonium-based ILs in water is extensively investigated through experimental techniques¹⁶ and molecular dynamics simulations.¹⁷ However, the precise control of their LCST phase transition temperature solely through ion design remains challenging. Here, we propose the tuning of hydrophilicity/hydrophobicity of ILs via host–guest chemistry to control their LCST phase transition temperature (T_LCST) in water (Fig. 1b).

Fig. 1 (a) A schematic image of LCST phase transition behaviour of some phosphonium-based ILs. (b) Phase diagram of IL/water mixtures and factors influencing the phase diagram. Structures of (c) [P₄₄₄₄][TsO] and (d) α-CD employed in the present study.

Tetrabutyl phosphonium p-toluenesulfonate ([P₄₄₄₄][TsO]) was selected as an IL showing LCST phase transition in water (Fig. 1c). As a host molecule for [P₄₄₄₄][TsO], α-cyclodextrin (α-CD) was selected (Fig. 1d). An aqueous solution of [P₄₄₄₄][TsO] ([P₄₄₄₄][TsO]_aq) was prepared by mixing 50 wt% of [P₄₄₄₄][TsO] and 50 wt% of water, which is reported to show an LCST phase transition at 54 °C.^5a To [P₄₄₄₄][TsO]_aq, x mol of α-CD per [P₄₄₄₄] cation were added, and the resultant solutions are denoted as “[P₄₄₄₄][TsO]_aq with α-CD(x)”.

Fig. 2 shows the images of [P₄₄₄₄][TsO]_aq with α-CD(x) (x = 0, 0.05 and 0.10) at various temperatures. [P₄₄₄₄][TsO]_aq with α-CD(0) shows an LCST phase transition at 55 °C, aligning with the reported literature,^5a while [P₄₄₄₄][TsO]_aq with α-CD(0.05 and 0.1) does not show LCST phase transition at 55 °C. Upon further heating, [P₄₄₄₄][TsO]_aq with α-CD(0.05) becomes turbid white at 66 °C and reaches a biphasic state at 70 °C. However, the LCST phase transition is not observed for [P₄₄₄₄][TsO]_aq with α-CD(0.10) even after heating to 70 °C. These results suggest that α-CD has the ability to effectively suppress the phase separation of [P₄₄₄₄][TsO] from water.

Fig. 2 Pictures of [P₄₄₄₄][TsO]_aq with α-CD(x) at various temperatures.

To further investigate the dependence of T_LCST on the α-CD molar ratio (x), we measured the transmittance of [P₄₄₄₄][TsO]_aq with α-CD(x) (x = 0 to 0.10) at different temperatures. The transmittance at 600 nm was measured at temperature intervals of 1 °C. In the monophasic state, where [P₄₄₄₄][TsO]_aq with α-CD(x) formed isotropic liquid solutions at 25 °C, nearly 100% transmittance was observed. Upon increasing the temperature to the LCST phase transition, the transmittance sharply decreased to 0% due to the formation of a cloudy state. The temperature at which the transmittance reached 50% was defined as the T_LCST. The temperature-dependent transmittance of [P₄₄₄₄][TsO]_aq with α-CD(x) is summarized in Fig. 3. While T_LCST is observed at 54 °C for the pristine [P₄₄₄₄][TsO]_aq solution, it is observed at higher temperatures for [P₄₄₄₄][TsO]_aq with α-CD(x). For example, [P₄₄₄₄][TsO]_aq with α-CD(0.01) shows a T_LCST at 56 °C, while [P₄₄₄₄][TsO]_aq with α-CD(0.05) exhibits a T_LCST at 64 °C. The increase in T_LCST is proportional to the α-CD concentration until x reaches a value of about 0.09. Importantly, for [P₄₄₄₄][TsO]_aq with α-CD(0.10), no LCST phase transition was observed within the temperature range of 25 to 85 °C. These results strongly suggest that the addition of α-CD significantly influences both the mixing enthalpy (ΔH_mix) and entropy (ΔS_mix).

Fig. 3 Transmittance change as a function of temperature for [P₄₄₄₄][TsO]_aq with α-CD(x) (x = 0 to 0.10) at a wavelength of 600 nm.

¹H-NMR measurements were performed for [P₄₄₄₄][TsO]_aq with α-CD(x) to investigate the host–guest interactions between [P₄₄₄₄][TsO] and α-CD. Here we denote some selected protons in the [P₄₄₄₄] cation as “A–C” the [TsO] anion as “d–f”, and α-CD as “Hn (n = 1–6)”, as shown in Fig. 4a. In general, the proton signals of H3 and H5, located inside the hydrophobic cavity of α-CD, show an upfield shift upon the incorporation of certain guest molecules.¹⁸ In this study, we analysed the changes in the ¹H-NMR spectrum of a saturated aqueous solution of α-CD with the incremental addition of [P₄₄₄₄][TsO]. The H3 and H5 peaks shifted upfield with increasing concentrations of [P₄₄₄₄][TsO], consistent with the reported trend (Fig. 4b). In contrast, the H2 and H4 protons, located outside the α-CD cavity, exhibited only slight chemical shifts, from 3.605 to 3.614 ppm and from 3.534 to 3.520 ppm, respectively. These results suggest that α-CD and [P₄₄₄₄][TsO] form host–guest complexes in water, facilitated by the incorporation of [P₄₄₄₄][TsO] to the hydrophobic cavity of α-CD. This interaction has the potential to modulate the LCST phase transition temperature.

Fig. 4 (a) Structures of [P₄₄₄₄][TsO] and α-CD. (b) ¹H-NMR spectra of a saturated aqueous solution of α-CD with/without [P₄₄₄₄][TsO]. (c) NOESY-NMR spectrum of [P₄₄₄₄][TsO]_aq with α-CD(1.0). (d) 1D NOE spectra of [P₄₄₄₄][TsO]_aq with α-CD(0.05) at various temperatures when the CH₃ group of the [P₄₄₄₄] cation is selectively excited.

Since [P₄₄₄₄][TsO] has four hydrophobic butyl groups on the [P₄₄₄₄] cation and a tosyl group on the [TsO] anion, there is a possibility that either or both of the [P₄₄₄₄] cation and the [TsO] anion act as the guest for α-CD in water. To determine the preferential guest, we performed a two-dimensional ¹H−¹H nuclear Overhauser effect spectroscopy (NOESY) measurement. It is a powerful technique for probing spatial interactions between different nuclear spins at distances of up to 0.5 nm. The NOESY-NMR spectrum of [P₄₄₄₄][TsO]_aq with α-CD(1.0) at 25 °C is shown in Fig. 4c. The spectrum shows diagonal peaks between various protons of [P₄₄₄₄][TsO] and α-CD. Additionally, weak cross-peaks between terminal protons of the alkyl chain of the [P₄₄₄₄] cation, such as “A” and “B”, and those of α-CD located inside the hydrophobic cavity, such as “H3” and “H5” are also present. The presence of these signals indicates that the [P₄₄₄₄] cation is spatially closer to α-CD, with an interatomic distance of less than 0.5 nm. Contrastingly, no cross-peaks are present between the methyl group proton (“d”) of the [TsO] anion and α-CD protons. These results suggest that the [P₄₄₄₄] cation is preferentially incorporated into α-CD compared to the [TsO] anion. This host–guest interaction should be one of the crucial driving forces for influencing the LCST phase transition behaviour of phosphonium-based ILs in water. Although there have been some precedent examples for the control of LCST phase transition behaviour of ILs in some organic solvents by the addition of some host molecules,¹⁹ there are few examples where the host–guest interaction was utilized for the control of LCST phase transition behaviour of ILs.²⁰

VT-1D NOE measurement was conducted for [P₄₄₄₄][TsO]_aq with α-CD(0.05). 1D NOE spectra, when the CH₃ group of the [P₄₄₄₄] cation is selectively excited, are shown in Fig. 4d. A NOE between the [P₄₄₄₄] cation and α-CD is clearly observed at around 3.7 ppm at 25 °C, which is consistent with the NOESY-NMR results shown in Fig. 4c. As the temperature increases, the NOE peak decreases stepwise. It disappears at around 59 °C entirely, which is equal to or lower than the LCST phase transition temperature determined by transmittance change (Fig. 3). Based on these results, we conclude as follows. α-CD makes a [P₄₄₄₄] cation more hydrophilic by including its hydrophobic alkyl chain as a guest. When the host–guest interaction is thermally weakened as temperature increases, the [P₄₄₄₄] cation recovers its intrinsic hydrophobicity, which triggers the LCST phase transition. For further understanding the effects of the host-guest interaction on the LCST phase transition, we are now exploring various experiments including dynamic light scattering, synchrotron X-ray scattering, and quasi-elastic neutron scattering measurements.

Conclusions

In summary, this study demonstrates that the LCST phase transition temperature of the phosphonium-based IL ([P₄₄₄₄][TsO]) in water can be effectively tuned through supramolecular host–guest interactions. The incorporation of [P₄₄₄₄][TsO] into the α-CD host led to a substantial increase in T_LCST by more than 20 °C. ¹H-NMR and NOESY measurements confirmed the formation of host–guest interactions between the [P₄₄₄₄] cation and α-CD. These results provide valid insights into the development of novel aquatic LCST materials with potential applications across various fields.

Author contributions

S. Y. and T. I. designed the study. S. Y. synthesised the compounds. S. Y. conducted most of the experiments. S. Y. and T. I. prepared the overall manuscript. All authors contributed to the writing of the manuscript. T. I. supervised the research.

Conflicts of interest

There are no conflicts to declare.

Data availability

Supplementary information is available. See DOI: https://doi.org/10.1039/D5ME00057B.

The data supporting this article have been included as part of the SI.

Acknowledgements

This work was supported by the Japan Science and Technology Agency (JST) FOREST (JPMJFR223C). This study was also supported by the JSPS KAKENHI grants (numbers JP22H04526, JP23K17937 and JP24K01547) from the Japan Society for the Promotion of Science.

Notes and references

1. (a) Electrochemical Aspects of Ionic Liquids, ed. H. Ohno, John Wiley & Sons, Hoboken, NJ, 2005; (b) D. R. MacFarlane, M. Forsyth, P. C. Howlett, M. Kar, S. Passerini, J. M. Pringle, H. Ohno, M. Watanabe, F. Yan, W. Zheng, S. Zhang and J. Zhang, Nat. Rev. Mater., 2016, 1, 15005.
2. M. Armand, F. Endres, D. R. MacFarlane, H. Ohno and B. Scrosati, Nat. Mater., 2009, 8, 621–629.
3. (a) H. Ohno, Bull. Chem. Soc. Jpn., 2006, 79, 1665–1680; (b) T. Ichikawa, T. Kato and H. Ohno, Chem. Commun., 2019, 55, 8205–8214.
4. K. Fukumoto and H. Ohno, Angew. Chem., Int. Ed., 2007, 46, 1852–1855.
5. (a) Y. Kohno, H. Arai, S. Saita and H. Ohno, Aust. J. Chem., 2011, 64, 1560–1567; (b) S. Saita, Y. Mieno, Y. Kohno and H. Ohno, Chem. Commun., 2014, 50, 15450–15452.
6. Y. Kohno, S. Saita, Y. Men, J. Yuan and H. Ohno, Polym. Chem., 2015, 6, 2163–2178.
7. (a) Y. Men, H. Schlaad and J. Yuan, ACS Macro Lett., 2013, 2, 456–459; (b) H.-Y. Li and Y.-H. Chu, Molecules, 2023, 28, 6817; (c) S. Montolio, L. Gonzáez, B. Altava, H. Tenhu, M. I. Burguete, E. García-Verdugo and S. V. Luis, Chem. Commun., 2014, 50, 10683–10686; (d) B. Ziółkowski and D. Diamond, Chem. Commun., 2013, 49, 10308–10310.
8. (a) S. T. Hemp, M. H. Allen Jr., M. D. Green and T. E. Long, Biomacromolecules, 2012, 13, 231–238; (b) V. L. Rose, F. Mastrotto and G. Mantovani, Polym. Chem., 2017, 8, 353–360.
9. (a) Y. Kohno, N. Nakamura and H. Ohno, Aust. J. Chem., 2012, 65, 1548–1553; (b) K. Ikeda, R. Ikari, N. Nakamura, H. Ohno and K. Fujita, J. Electrochem. Soc., 2018, 165, G96–G100.
10. L. Wang, X. Chen, J. Liu and Z. Tan, J. Mol. Liq., 2021, 340, 117295–117303.
11. Y. Qiao, W. Ma, N. Theyssen, C. Chen and Z. Hou, Chem. Rev., 2017, 117, 6881–6928.
12. A. Tudora, J. Saezb, L. Florea, F. Benito-Lopez and D. Diamond, Sens. Actuators, B, 2017, 247, 749–755.
13. H.-X. Xu, D. C. Wang, C.-H. Ho, M.-C. Chang, R.-Y. Horng, T.-M. Liang and P.-I. Liu, Desalin. Water Treat., 2022, 258, 55–63.
14. (a) W.-D. Chen, D.-W. Zhang, W.-T. Gong, Y. Lin and G.-L. Ning, Spectrochim. Acta, Part A, 2013, 110, 471–473; (b) H. Iwasawa, D. Uchida, Y. Hara, M. Tanaka, N. Nakamura, H. Ohno and T. Ichikawa, Adv. Opt. Mater., 2023, 11, 2301197.
15. S. Saita, Y. Kohno, N. Nakamura and H. Ohno, Chem. Commun., 2013, 49, 8988–8990.
16. (a) R. Wang, W. Leng, Y. Gao and L. Yu, RSC Adv., 2014, 4, 14055–14062; (b) H. Kang, D. E. Suich, J. F. Davies, A. D. Wilson, J. J. Urban and R. Kostecki, Commun. Chem., 2019, 2, 1–11.
17. (a) H. O. Mohammed, A. de Cozar and R. Zangi, J. Chem. Inf. Model., 2025, 65, 785–797; (b) Y. Zhao, L. Tian, Y. Pei, H. Wang and J. Wang, Ind. Eng. Chem. Res., 2018, 57, 12935–12941.
18. H.-J. Schneider, F. Hacket, V. Rüdiger and H. Ikeda, Chem. Rev., 1998, 98, 1755–1786.
19. (a) S. Dong, J. Heyda, J. Yuan and C. A. Schalley, Chem. Commun., 2016, 52, 7970–7973; (b) S. Dong, B. Zheng, Y. Yao, C. Han, J. Yuan, M. Antonietti and F. Huang, Adv. Mater., 2013, 25, 6864–6867.
20. S. Amajjahe and H. Ritter, Macromolecules, 2008, 41, 3250–3253.

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