Cation-anion-water interactions in aqueous mixtures of imidazolium based ionic liquids

We have examined the cation-anion-water interactions in aqueous mixtures of imidazolium ionic liquids (ILs) over the whole composition range using FTIR spectroscopy. Changes in the peak positions or band areas of OH vibrational modes of water and CH vibrational modes of imidazolium cation as a function of IL concentration indicated a diminishing trend in hydrogen-bonding network of water and qualitative changes in solution structures. ¹H NMR chemical shifts of C(2)H, HC(4)C(5)H and alkyl chain protons of imidazolium cation provided useful information about the comparative strength of cation-anion-water interactions.     

The Influence of Ionic Liquids Adsorption on the Electronic and Optical Properties of Phosphorene and Arsenene with Different Phases: A Computational Study

Density functional theory (DFT) calculations have been performed to investigate the interfacial interactions of ionic liquids (ILs) on the α- and β-phases of phosphorene (P) and arsenene (As). Nine representative ILs based on the combinations of 1-ethyl-3-methylimidazolium ([EMIM]⁺), N-methylpyridinium ([MPI]⁺), and trimethylamine ([TMA]⁺) cations paired to tetrafluoroborate ([BF₄]⁻), trifluoromethanesulfonate ([TFO]⁻), and chloridion (Cl⁻) anions were used as adsorbates on the 2D P and As nanosheets with different phases to explore the effect of IL adsorption on the electronic and optical properties of 2D materials. The calculated structure, adsorption energy, and charge transfer suggest that the interaction between ILs and P and As nanosheets is dominated by noncovalent forces, and the most stable adsorption structures are characterized by the simultaneous interaction of the cation and anion with the surface, irrespective of the types of ILs and surfaces. Furthermore, the IL adsorption leads to the larger change in the electronic properties of β-phase P and As than those of their α-phase counterparts, which demonstrates that the adsorption properties are not only related to the chemical elements, but also closely related to the phase structures. The present results provide insight into the further applications of ILs and phosphorene (arsenene) hybrid materials.     

Novel Phosphonium-Based Ionic Liquid Electrolytes for Battery Applications

In this study, we address the fundamental question of the physicochemical and electrochemical properties of phosphonium-based ionic liquids containing the counter-ions bis(trifluoromethanesulfonyl)imide ([TFSI]⁻) and bis(fluorosulfonyl)imide ([FSI]⁻). To clarify these structure–property as well as structure–activity relationships, trimethyl-based alkyl- and ether-containing phosphonium ILs were systematically synthesized, and their properties, namely density, flow characteristics, alkali metal compatibility, oxidative stability, aluminum corrosivity as well as their use in Li-ion cells were examined comprehensively. The variable moiety on the phosphonium cation exhibited a chain length of four and five, respectively. The properties were discussed as a function of the side chain, counter-ion and salt addition ([Li][TFSI] or [Li][FSI]). High stability coupled with good flow characteristics were found for the phosphonium IL [P1114][TFSI] and the mixture [P1114][TFSI] + [Li][TFSI], respectively.     

DNA小沟结合药物DB818的分子动力学模拟和结合自由能分析

采用分子动力学模拟了DNA小沟结合芳香二脒药物DB818形成的复合物. 通过5 ns的模拟研究表明: DB818药物分子可紧密结合在DNA的AATTC小沟区域, 和双螺旋d[CGCGAATTCGCG]2形成稳定的复合物. 由于噻吩硫原子的弱电负性, 使DB818能够以更大的伸展程度与DNA的小沟结合, 形成更强的结合力. DB818苯并咪唑的氮原子能够与DNA 7位和19位T碱基上的氧原子形成两个稳定的氢键, 同时, DB818末端氨基氮原子分别与DNA 的20位T碱基的氧原子和9位C碱基的氧原子形成两个氢键. 另外, 运用MM_PBSA方法计算了DB293-DNA和DB818-DNA复合物的结合自由能, 计算结合能与实验值能较好的吻合, 通过比较其结合自由能, 从热力学能量角度说明了DB818有较大的熵值与较小的焓值贡献, 从而与DNA小沟结合的结合力比DB293强. 本文在分子水平上提供了DB818直接与双螺旋DNA相互作用的结构及复合物的动态变化情况, 为设计出更高生物活性的DNA小沟结合剂提供一定的理论依据.     

Origin of Salt Effects in SN2 Fluorination Using KF Promoted by Ionic Liquids: Quantum Chemical Analysis

Quantum chemical analysis is presented, motivated by Grée and co-workers’ observation of salt effects [Adv. Synth. Catal. 2006, 348, 1149–1153] for S_N2 fluorination of KF in ionic liquids (ILs). We examine the relative promoting capacity of KF in [bmim]PF₆ vs. [bmim]Cl by comparing the activation barriers of the reaction in the two ILs. We also elucidate the origin of the experimentally observed additional rate acceleration in IL [bmim]PF₆ achieved by adding KPF₆. We find that the anion PF₆⁻ in the added salt acts as an extra Lewis base binding to the counter-cation K⁺ to alleviate the strong Coulomb attractive force on the nucleophile F⁻, decreasing the Gibbs free energy of activation as compared with that in its absence, which is in good agreement with experimental observations of rate enhancement. We also predict that using 2 eq. KF together with an eq. KPF₆ would further activate S_N2 fluorination     

Self‐diffusion and interactions in mixtures of imidazolium bis(mandelato)borate ionic liquids with polyethylene glycol: 1H NMR study

We used ¹H nuclear magnetic resonance pulsed‐field gradient to study the self‐diffusion of polyethylene glycol (PEG) and ions in a mixture of PEG and imidazolium bis(mandelato)borate ionic liquids (ILs) at IL concentrations from 0 to 10 wt% and temperatures from 295 to 370 K. PEG behaves as a solvent for these ILs, allowing observation of separate lines in ¹H NMR spectra assigned to the cation and anion as well as to PEG. The diffusion coefficients of PEG, as well as the imidazolium cation and bis(mandelato)borate (BMB) anion, differ under all experimental conditions tested. This demonstrates that the IL in the mixture is present in at least a partially dissociated state, while the lifetimes of the associated states of the ions and ions with PEG are less than ~30 ms. Generally, increasing the concentration of the IL leads to a decrease in the diffusion coefficients of PEG and both ions. The diffusion coefficient of the anion is less than that of the cation; the molecular mass dependence of diffusion of ions can be described by the Stokes–Einstein model. NMR chemical shift alteration analysis showed that the presence of PEG changes mainly the chemical shifts of protons belonging to imidazole ring of the cation, while chemical shifts of protons of anions and PEG remain unchanged. This demonstrated that the imidazolium cation interacts mainly with PEG, which most probably occurs through the oxygen of PEG and the imidazole ring. The BMB anion does not strongly interact with PEG, but it may be indirectly affected by PEG through interaction with the cation, which directly interacts with PEG. Copyright © 2015 John Wiley & Sons, Ltd.     

DFT Study of the Geometrical and Electronic Structures of Geminal Dicationic Ionic Liquids 1,3‐Bis[3‐methylimidazolium‐1‐yl]hexane Halides

In this work, the geometrical and electronic properties of the mono cationic ionic liquid 1‐hexyl‐3‐methylimidazolium halides ([C₆(mim)]⁺_X^?, X=Cl, Br and I) and dicationic ionic liquid 1,3‐bis[3‐methylimidazolium‐1‐yl]hexane halides ([C₆(mim)₂X₂], X=Cl, Br and I) were studied using the density functional theory (DFT). The most stable conformer of these two types ionic liquids (IL) are determined and compared with each other. Results show that in the most stable conformers, in both monocationic ILs and dicationic ILs, the Cl^? and Br^? anions prefer to locate almost in the plane of the imidazolium ring whereas the I^? anion prefers nearly vertical location respect to the imidazolium ring plan. Comparison of hydrogen bonding and ionic interactions in these two types of ionic liquids reveals that these ionic liquids can be formed hydrogen bond by Cl^? and Br^? anion. The calculated thermodynamic functions show that the interaction of cation — anion pair in the dicationic ionic liquids are more than monocationic ionic liquids and these interactions decrease with increasing the halide anion atomic weight.     

Adsorption and Purification of Baicalin from Scutellaria baicalensis Georgi Extract by Ionic Liquids (ILs) Grafted Silica

Baicalin which has multiple biological activities is the main active component of the root of Scutellaria baicalensis Georgi (SBG). Although its isolation and purification by adsorption methods have aroused much interest of the scientific community, it suffered from the poor selectivity of the adsorbents. In this work, an environmentally benign method was developed to prepare ionic liquids (ILs) grafted silica by using IL 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C₄mim]NTf₂) and ethanol as reaction media. The IL 1-propyl-3-methylimidazolium chloride ([C₃mim]Cl) grafted silica ([C₃mim]⁺Cl⁻@SiO₂) was used to adsorb and purify baicalin from the root extract of Scutellaria baicalensis Georgi (SBG). Experimental results indicated that the adsorption equilibrium can be quickly achieved (within 10 min). The adsorption behavior of [C₃mim]⁺Cl⁻@SiO₂ for baicalin was in good agreement with Langmuir and Freundlich models and the adsorption was a physisorption process as suggested by Dubinin–Radushkevich model. Compared with commercial resins, [C₃mim]⁺Cl⁻@SiO₂ showed the strongest adsorption ability and highest selectivity. After desorption and crystallization, a purity of baicalin as high as 96.5% could be obtained. These results indicated that the ILs grafted silica materials were promising adsorbents for the adsorption and purification of baicalin and showed huge potential in the purification of other bioactive compounds from natural sources.     

On the different roles of anions and cations in the solvation of enzymes in ionic liquids

The solvation of the enzyme Candida antarctica lipase B (CAL-B) was studied in eight different ionic liquids (ILs). The influence of enzyme-ion interactions on the solvation of CAL-B and the structure of the enzyme-IL interface are analyzed. CAL-B and ILs are described with molecular dynamics (MD) simulations in combination with an atomistic empirical force field. The considered cations are based on imidazolium or guanidinium that are paired with nitrate, tetrafluoroborate or hexafluorophosphate anions. The interactions of CAL-B with ILs are dominated by Coulomb interactions with anions, while the second largest contribution stems from van der Waals interactions with cations. The enzyme-ion interaction strength is determined by the ion size and the magnitude of the ion surface charge. The solvation of CAL-B in ILs is unfavorable compared to water because of large formation energies for the CAL-B solute cages in ILs. The internal energy in the IL and of CAL-B increases linearly with the enzyme-ion interaction strength. The average electrostatic potential on the surface of CAL-B is larger in ILs than in water, due to a weaker screening of charged enzyme residues. Ion densities increased moderately in the vicinity of charged residues and decreased close to non-polar residues. An aggregation of long alkyl chains close to non-polar regions and the active site entrance of CAL-B are observed in one IL that involved long non-polar decyl groups. In ILs that contain 1-butyl-3-methylimidazolium cations, the diffusion of one or two cations into the active site of CAL-B occurs during MD simulations. This suggests a possible obstruction of the active site in these ILs. Overall, the results indicate that small ions lead to a stronger electrostatic screening within the solvent and stronger interactions with the enzyme. Also a large ion surface charge, when more hydrophilic ions are used, increases enzyme-IL interactions. An increase of these interactions destabilizes the enzyme and impedes enzyme solvation due to an increase in solute cage formation energies.     

Study of the Alkyl Chain Length on Laccase Stability and Enzymatic Kinetic with Imidazolium Ionic Liquids

The activity and stability of laccase and their kinetic mechanisms in water soluble ionic liquids (ILs): 1-butyl-3-methyl imidazolium chloride [C₄mim][Cl], 1-octyl-3-methyl imidazolium chloride [C₈mim][Cl], and 1-decyl-3-methyl imidazolium chloride [C₁₀mim][Cl] were investigated. The results show that an IL concentration up to 10% is satisfactory for initial laccase activity at pH 9.0. The laccase stability was well maintained in [C₄mim][Cl] IL when compared to the control. The inactivation of laccase increases with the length of the alkyl chain in the IL: [C₁₀mim][Cl] > [C₈mim][Cl] > [C₄mim][Cl]. The kinetic studies in the presence of ABTS as substrate allowed calculating the Michaelis–Menten parameters. Among the ILs, [C₄mim][Cl] was the suitable choice attending to laccase activity and stability. Alkyl chains in the ions of ILs have a deactivating effect on laccase, which increases strongly with the length of the alkyl chain.     

Synthesis of ricinoleate anion based ionic liquids and their application as green lubricating oil additives

Ricinoleate anion based ionic liquids (ILs) were synthesized from four different nitrogen containing cationic counterparts such as tetrabutylammonium, tetrapropylammonium, cetyltrimethylammonium, imidazolium. Tribological performance of synthesized ILs were evaluated using four ball tribo tester by blending with two lubricant base oils namely epoxy2-ethylhexyl esters of karanja fatty acids (EKE) and dioctyl sebacate (DOS). Antiwear behaviour was explored by varying different factors including concentration, applied load and rotation speed. It was found that the synthesized ILs in base oil significantly reduced the wear scar diameter by 17–25% at 0.8 wt% and a remarkable reduction in wear scar diameter was observed for all the tested applied load (40 to 80 kg) and rotation speed (1200 to 1742 rpm). Further, the load carrying capacity of base oil was improved by 25–43% at 1.25 wt% of IL dosage. The imidazolium cation containing IL outperform tribological performance among all the ILs being studied. The morphology of worn surface after the wear tests and deposition of elementals on the worn surface lubricated with neat base oil and IL blended base oil was studied by scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX).     

A Comparative Study of Pyrolysis Liquids by Slow Pyrolysis of Industrial Hemp Leaves,Hurds and Roots

This study assessed the pyrolysis liquids obtained by slow pyrolysis of industrial hemp leaves, hurds, and roots. The liquids recovered between a pyrolysis temperature of 275–350 °C, at two condensation temperatures 130 °C and 70 °C, were analyzed. Aqueous and bio-oil pyrolysis liquids were produced and analyzed by proton nuclear magnetic resonance (NMR), gas chromatography–mass spectrometry (GC-MS), and atmospheric pressure photoionization Fourier transform ion cyclotron resonance mass spectrometry (APPI FT-ICR MS). NMR revealed quantitative concentrations of the most abundant compounds in the aqueous fractions and compound groups in the oily fractions. In the aqueous fractions, the concentration range of acetic acid was 50–241 gL⁻¹, methanol 2–30 gL⁻¹, propanoic acid 5–20 gL⁻¹, and 1-hydroxybutan-2-one 2 gL⁻¹. GC-MS was used to compare the compositions of the volatile compounds and APPI FT-ICR MS was utilized to determine the most abundant higher molecular weight compounds. The different obtained pyrolysis liquids (aqueous and oily) had various volatile and nonvolatile compounds such as acetic acid, 2,6-dimethoxyphenol, 2-methoxyphenol, and cannabidiol. This study provides a detailed understanding of the chemical composition of pyrolysis liquids from different parts of the industrial hemp plant and assesses their possible economic potential.     

Berberrubine Phosphate: A Selective Fluorescent Probe for Quadruplex DNA

A phosphate-substituted, zwitterionic berberine derivative was synthesized and its binding properties with duplex DNA and G4-DNA were studied using photometric, fluorimetric and polarimetric titrations and thermal DNA denaturation experiments. The ligand binds with high affinity toward both DNA forms (K_b = 2–7 × 10⁵ M⁻¹) and induces a slight stabilization of G4-DNA toward thermally induced unfolding, mostly pronounced for the telomeric quadruplex 22AG. The ligand likely binds by aggregation and intercalation with ct DNA and by terminal stacking with G4-DNA. Thus, this compound represents one of the rare examples of phosphate-substituted DNA binders. In an aqueous solution, the title compound has a very weak fluorescence intensity (Φ_fl < 0.01) that increases significantly upon binding to G4-DNA (Φ_fl = 0.01). In contrast, the association with duplex DNA was not accompanied by such a strong fluorescence light-up effect (Φ_fl < 0.01). These different fluorimetric responses upon binding to particular DNA forms are proposed to be caused by the different binding modes and may be used for the selective fluorimetric detection of G4-DNA.     

Head-Space SPME for the Analysis of Organophosphorus Insecticides by Novel Silica IL-Based Fibers in Real Samples

This work demonstrates the suitability of a newly developed ionic liquid (IL)-based silica SPME fiber for the determination of seven organophosphorus insecticides in cucumber and grapefruit samples by headspace solid-phase microextraction (HS-SPME) with a gas chromatography–flame ionization detector (FID). The sol-gel method released four different sorbent coatings, which were obtained based on a silica matrix containing ILs immobilized inside its pores. In order to obtain ionogel fibers, the following ionic liquids were utilized: 1-Butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide; Butyltriethyl ammonium bis(trifluoromethylsulfonyl)imide; 1-(2-Methoxyethyl)-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, and 1-Benzyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide. The developed fibers were applied for the extraction of seven different insecticides from liquid samples. The most important extraction parameters of HS-SPME coupled with the GC-FID method were optimized with a central composite design. The new SPME fiber demonstrated higher selectivity for extracting the analyzed insecticides compared with commercially available fibers. The limit of detection was in the range of 0.01–0.93 μg L⁻¹, the coefficients of determination were >0.9830, and 4.8–10.1% repeatability of the method was found. Finally, the obtained ionogel fibers were utilized to determine insecticides in fresh cucumber and grapefruit juices.     

Understanding the mechanism of cellulose dissolution in 1-butyl-3-methylimidazolium chloride ionic liquid via quantum chemistry calculations and molecular dynamics simulations

While N,N′-dialkylimidazolium ionic liquids (ILs) have been well-established as effective solvents for dissolution and processing of cellulose, the detailed mechanism at the molecular level still remains unclear. In this work, we present a combined quantum chemistry and molecular dynamics simulation study on how the ILs dissolve cellulose. On the basis of calculations on 1-butyl-3-methylimidazolium chloride, one of the most effective ILs dissolving cellulose, we further studied the molecular behavior of cellulose models (i.e. cellulose oligomers with degrees of polymerization n = 2, 4, and 6) in the IL, including the structural features and hydrogen bonding patterns. The collected data indicate that both chloride anions and imidazolium cations of the IL interact with the oligomer via hydrogen bonds. However, the anions occupy the first coordination shell of the oligomer, and the strength and number of hydrogen bonds and the interaction energy between anions and the oligomer are much larger than those between cations and the oligomer. It is observed that the intramolecular hydrogen bond in the oligomer is broken under the combined effect of anions and cations. The present results emphasize that the chloride anions play a critically important role and the imidazolium cations also present a remarkable contribution in the cellulose dissolution. This point of view is different from previous one that only underlines the importance of the chloride anions in the cellulose dissolution. The present results improve our understanding for the cellulose dissolution in imidazolium chloride ILs.     

Effects of Cationic Structure on Cellulose Dissolution in Ionic Liquids: A Molecular Dynamics Study

In recent years, great progress has been made in the dissolution of cellulose with ionic liquids (ILs). However, the mechanism of cellulose dissolution, especially the role the IL cation played in the dissolution process, has not been clearly understood. Herein, the mixtures of cellulose with a series of imidazolium‐based chloride ionic liquids and 1‐butyl‐3‐methyl pyridinium chloride ([C₄mpy]Cl) were simulated to study the effect that varying the heterocyclic structure and alkyl chain length of the IL cation has on the dissolution of cellulose. It was shown that the dissolution of cellulose in [C₄mpy]Cl is better than that in [C₄mim]Cl. For imidazolium‐based ILs, the shorter the alkyl chain is, the higher the solubility will be. In addition, an all‐atom force field for 1‐allyl‐3‐methyl imidazolium cation ([Amim]⁺) was developed, for the first time, to investigate the effect the electron‐withdrawing group within the alkyl chain of the IL cation has on the dissolution of cellulose. It was found that the interaction energy between [Amim]⁺ and cellulose was greater than that between [C₃mim]⁺ and cellulose, indicating that the presence of electron‐withdrawing group in alkyl chain of the cation enhanced the interaction between the cation and cellulose due to the increase of electronegativity of the cations. These findings are used to assess the cationic effect on the dissolution of cellulose in ILs. They are also expected to be important for rational design of novel ILs for efficient dissolution of cellulose.     

In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (Mpro) Inhibitors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug leads, marine-derived metabolites are reported here as prospective SARS-CoV-2 inhibitors. Two hundred and twenty-seven terpene natural products isolated from the biodiverse Red-Sea ecosystem were screened for inhibitor activity against the SARS-CoV-2 main protease (M^pro) using molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area binding energy calculations. On the basis of in silico analyses, six terpenes demonstrated high potency as M^pro inhibitors with ΔG_binding ≤ −40.0 kcal/mol. The stability and binding affinity of the most potent metabolite, erylosides B, were compared to the human immunodeficiency virus protease inhibitor, lopinavir. Erylosides B showed greater binding affinity towards SARS-CoV-2 M^pro than lopinavir over 100 ns with ΔG_binding values of −51.9 vs. −33.6 kcal/mol, respectively. Protein–protein interactions indicate that erylosides B biochemical signaling shares gene components that mediate severe acute respiratory syndrome diseases, including the cytokine- and immune-signaling components BCL2L1, IL2, and PRKC. Pathway enrichment analysis and Boolean network modeling were performed towards a deep dissection and mining of the erylosides B target–function interactions. The current study identifies erylosides B as a promising anti-COVID-19 drug lead that warrants further in vitro and in vivo testing.     

Unravelling the Interactions of Magnetic Ionic Liquids by Energy Decomposition Schemes: Towards a Transferable Polarizable Force Field

This work aims at unravelling the interactions in magnetic ionic liquids (MILs) by applying Symmetry-Adapted Perturbation Theory (SAPT) calculations, as well as based on those to set-up a polarisable force field model for these liquids. The targeted MILs comprise two different cations, namely: 1-butyl-3-methylimidazolium ([Bmim]⁺) and 1-ethyl-3-methylimidazolium ([Emim]⁺), along with several metal halides anions such as [FeCl₄]⁻, [FeBr₄]⁻, [ZnCl₃]⁻ and [SnCl₄]²⁻ To begin with, DFT geometry optimisations of such MILs were performed, which in turn revealed that the metallic anions prefer to stay close to the region of the carbon atom between the nitrogen atoms in the imidazolium fragment. Then, a SAPT study was carried out to find the optimal separation of the monomers and the different contributions for their interaction energy. It was found that the main contribution to the interaction energy is the electrostatic interaction component, followed by the dispersion one in most of the cases. The SAPT results were compared with those obtained by employing the local energy decomposition scheme based on the DLPNO-CCSD(T) method, the latter showing slightly lower values for the interaction energy as well as an increase of the distance between the minima centres of mass. Finally, the calculated SAPT interaction energies were found to correlate well with the melting points experimentally measured for these MILs.     

Exploring conformational preferences of proteins: ionic liquid effects on the energy landscape of avidin

In this work we experimentally investigate solvent and temperature induced conformational transitions of proteins and examine the role of ion–protein interactions in determining the conformational preferences of avidin, a homotetrameric glycoprotein, in choline-based ionic liquid (IL) solutions. Avidin was modified by surface cationisation and the addition of anionic surfactants, and the structural, thermal, and conformational stabilities of native and modified avidin were examined using dynamic light scattering, differential scanning calorimetry, and thermogravimetric analysis experiments. The protein-surfactant nanoconjugates showed higher thermostability behaviour compared to unmodified avidin, demonstrating distinct conformational ensembles. Small-angle X-ray scattering data showed that with increasing IL concentration, avidin became more compact, interpreted in the context of molecular confinement. To experimentally determine the detailed effects of IL on the energy landscape of avidin, differential scanning fluorimetry and variable temperature circular dichroism spectroscopy were performed. We show that different IL solutions can influence avidin conformation and thermal stability, and we provide insight into the effects of ILs on the folding pathways and thermodynamics of proteins. To further study the effects of ILs on avidin binding and correlate thermostability with conformational heterogeneity, we conducted a binding study. We found the ILs examined inhibited ligand binding in native avidin while enhancing binding in the modified protein, indicating ILs can influence the conformational stability of the distinct proteins differently. Significantly, this work presents a systematic strategy to explore protein conformational space and experimentally detect and characterise ‘invisible’ rare conformations using ILs.

Revealing solvent and temperature induced conformational transitions of proteins and the role of ion–protein interactions in determining the conformational preferences of avidin in ionic liquids.