Li Hsin-Yi, Chu Yen-Ho
Department of Chemistry and Biochemistry, National Chung Cheng University, Chiayi 62102, Taiwan.
Molecules. 2023 Sep 27;28(19):6817. doi: 10.3390/molecules28196817.
Ionic liquids (ILs) are a class of low-melting molten salts (<100 °C) constituted entirely of ions, and their research has gained tremendous attention in line with their remarkably growing applications (>124,000 publications dated 30 August 2023 from the Web of Science). In this review, we first briefly discussed the recent developments and unique characteristics of ILs and zwitterionic liquids (ZILs). Compared to molecular solvents and other conventional organic compounds, (zwitter) ionic liquids carry negligible volatility and are potentially recyclable and reusable. For structures, both ILs and ZILs can be systematically tailor-designed and engineered and are synthetically fine-tunable. As such, ionic liquids, including chiral, supported, task-specific ILs, have been widely used as powerful ionic solvents as well as valuable additives and catalysts for many chemical reactions. Moreover, ILs have demonstrated their value for use as polymerase chain reaction (PCR) enhancers for DNA amplification, chemoselective artificial olfaction for targeted VOC analysis, and recognition-based affinity extraction. As the major focus of this review, we extensively discussed that small-molecule thermoresponsive ILs (TILs) and ZILs (zwitterionic TILs) are new types of smart materials and can be expeditiously discovered through the structure and phase separation (SPS) relationship study by the combinatorial approach. Using this SPS platform developed in our laboratory, we first depicted the rapid discovery of N,N-dialkylcycloammonium and 1,3,4-trialkyl-1,2,3-triazolium TILs that concomitantly exhibited LCST (lower critical solution temperature) phase transition in water and displayed biochemically attractive values. Both smart IL materials were suited for applications to proteins and other biomolecules. Zwitterionic TILs are ZILs whose cations and anions are tethered together covalently and are thermoresponsive to temperature changes. These zwitterionic TIL materials can serve as excellent extraction solvents, through temperature change, for biomolecules such as proteins since they differ from the common TIL problems often associated with unwanted ion exchanges during extractions. These unique structural characteristics of zwitterionic TIL materials greatly reduce and may avoid the denaturation of proteins under physiological conditions. Lastly, we argued that both rational structural design and combinatorial library synthesis of small-molecule TIL materials should take into consideration the important issues of their cytotoxicity and biosafety to the ecosystem, potentially causing harm to the environment and directly endangering human health. Finally, we would concur that before precise prediction and quantitative simulation of TIL structures can be realized, combinatorial chemistry may be the most convenient and effective technology platform to discover TIL expeditiously. Through our rational TIL design and combinatorial library synthesis and screening, we have demonstrated its power to discover novel chemical structures of both TILs and zwitterionic TILs. Undoubtedly, we will continue developing new small-molecule TIL structures and studying their applications related to other thermoresponsive materials.
离子液体（ILs）是一类完全由离子构成的低熔点熔盐（<100°C），随着其应用的显著增长（截至2023年8月30日，来自科学网的相关出版物超过124,000篇），它们的研究受到了极大关注。在本综述中，我们首先简要讨论了离子液体和两性离子液体（ZILs）的最新进展和独特特性。与分子溶剂和其他传统有机化合物相比，（两性）离子液体的挥发性可忽略不计，并且具有潜在的可回收和再利用性。在结构方面，离子液体和两性离子液体都可以进行系统的定制设计和工程化，并且在合成上具有精细的可调性。因此，离子液体，包括手性离子液体、负载型离子液体、特定任务离子液体，已被广泛用作强大的离子溶剂以及许多化学反应的有价值的添加剂和催化剂。此外，离子液体已证明其在用作DNA扩增的聚合酶链反应（PCR）增强剂、用于靶向挥发性有机化合物分析的化学选择性人工嗅觉以及基于识别的亲和萃取方面的价值。作为本综述的主要重点，我们广泛讨论了小分子热响应离子液体（TILs）和两性离子热响应离子液体（两性离子TILs）是新型智能材料，并且可以通过组合方法对结构和相分离（SPS）关系的研究快速发现。利用我们实验室开发的这个SPS平台，我们首先描述了N，N - 二烷基环铵和1,3,4 - 三烷基 - 1,2,3 - 三唑鎓TILs的快速发现，它们在水中同时表现出低临界溶液温度（LCST）相变，并显示出具有生物化学吸引力的值。这两种智能离子液体材料都适用于蛋白质和其他生物分子的应用。两性离子TILs是阳离子和阴离子通过共价键连接在一起并且对温度变化具有热响应性的两性离子液体。这些两性离子TIL材料可以通过温度变化用作蛋白质等生物分子的优良萃取溶剂，因为它们不同于常见的TIL问题，这些问题通常与萃取过程中不需要的离子交换有关。两性离子TIL材料的这些独特结构特征极大地减少并且可能避免蛋白质在生理条件下的变性。最后，我们认为小分子TIL材料的合理结构设计和组合库合成都应考虑其对生态系统的细胞毒性和生物安全性等重要问题，这可能对环境造成危害并直接危及人类健康。最后，我们同意在能够实现TIL结构的精确预测和定量模拟之前，组合化学可能是快速发现TIL的最方便和有效的技术平台。通过我们合理的TIL设计、组合库合成和筛选，我们已经展示了其发现TILs和两性离子TILs新型化学结构的能力。毫无疑问，我们将继续开发新的小分子TIL结构并研究它们与其他热响应材料相关的应用。
