Ionic liquids in separation techniques

Ionic liquids in separation techniques

Available online at www.sciencedirect.com Journal of Chromatography A, 1184 (2008) 6–18 Review Ionic liquids in separation techniques b , S. Carda-...

573KB Sizes 0 Downloads 79 Views

Available online at www.sciencedirect.com

Journal of Chromatography A, 1184 (2008) 6–18

Review

Ionic liquids in separation techniques b , S. Carda-Broch c ´ A. Berthod a,∗ , M.J. Ruiz-Angel a

Laboratoire des Sciences Analytiques, Universit´e de Lyon, CNRS, Bat. CPE, 69622 Villeurbanne, France b Departament de Qu´ımica Anal´ıtica, Universitat de Val` encia, c/ Dr. Moliner 50, 46100 Burjassot, Spain c Departament de Qu´ımica F´ısica i Anal´ıtica, Universitat Jaume I, Campus de Riu Sec, s/n, 12080 Castell´o, Spain Available online 8 December 2007

Abstract The growing interest in ionic liquids (ILs) has resulted in an exponentially increasing production of analytical applications. The potential of ILs in chemistry is related to their unique properties as non-molecular solvents: a negligible vapor pressure associated to a high thermal stability. ILs found uses in different sub-disciplines of analytical chemistry. After drawing a rapid picture of the physicochemical properties of selected ILs, this review focuses on their use in separation techniques: gas chromatography (GC), liquid chromatography (LC) and electrophoretic methods (CE). In LC and CE, ILs are not used as pure solvents, but rather diluted in aqueous solutions. In this situation ILs are just salts. They are dual in nature. Too often the properties of the cations are taken as the properties of the IL itself. The lyotropic theory is recalled and the effects of a chaotropic anion are pointed out. Many results can be explained considering all ions present in the solution. Ion-pairing and ion-exchange mechanisms are always present, associated with hydrophobic interactions, when dealing with IL in diluted solutions. Chromatographic and electrophoretic methods are also mainly employed for the control and monitoring of ILs. These methods are also considered. ILs will soon be produced on an industrial scale and it will be necessary to develop reliable analytical procedures for their analysis and control. © 2007 Elsevier B.V. All rights reserved. Keywords: Room-temperature ionic liquids; Chromatographic techniques; Mobile phase additives; Capillary electrophoresis; Monitoring; Reviews

Contents 1. 2. 3.

4.

5.



Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Physicochemical properties of ionic liquids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Gas chromatography and ionic liquids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Classical coated stationary phases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Special ionic liquid-based gas chromatography stationary phases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Liquid chromatography and ionic liquids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Ionic liquids as reversed-phase liquid chromatography organic modifiers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Ionic liquids as mobile phase additives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Ionic liquids as liquid chromatography stationary phases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4. Use of ionic liquids in counter-current chromatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ionic liquids in capillary electrophoresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. Ionic liquids as capillary wall covalent coating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2. Ionic liquids as background electrolyte and dynamic wall coating in aqueous capillary electrophoresis . . . . . . . . . . . . . . . . . . . . . . 5.3. Ionic liquids as background electrolytes in non-aqueous capillary electrophoresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4. Use of chiral ionic liquids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5. Micellar electrokinetic chromatography with ionic liquids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Corresponding author. Tel.: +33 472 431 434; fax: +33 472 431 078. E-mail address: [email protected] (A. Berthod).

0021-9673/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.chroma.2007.11.109

7 7 10 10 10 10 11 11 13 13 14 14 14 14 14 14

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

6.

7.

Separation methods for ionic liquid analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.1. Reversed-phase liquid chromatography of ionic liquids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2. Analytical methods for ion determination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction Ionic liquids (ILs) are very simply molten salts. As salts they are by essence made of cations and anions. Inorganic salts such as the sodium halogens are solid with melting point well above 500 ◦ C (Table 1). The novelty of the new non-molecular class of IL solvents is the low melting temperature of these salts. To be part of the IL family, a given salt must have a melting point arbitrarily fixed at or below 100 ◦ C. If the salt melting point is below room temperature (∼25 ◦ C), the IL is called room-temperature ionic liquid (RTIL) [1]. The term ionic liquid covers inorganic as well as organic molten salts. However, the recent literature deals with RTILs made of a bulky nitrogenor phosphorous-containing dissymmetrical organic cation such as alkyl-imidazolium, pyridinium or pyrrolidinium, ammonium or phosphonium cations, and a variety of organic, triflate, dicyanamide, acetate, trifluoroacetate, trifluoromethylsulfate or inorganic, bromide, chloride, nitrate, perchlorate, chloroaluminate, tetrafluoroborate, or hexafluorophosphate anions [2,3]. Kenneth R. Seddon of Queen University (Belfast, Northern Ireland) recently stated: “Years ago, I predicted that ionic liquids would change the face of organic chemistry. It is clear now that they have the potential to revolutionize all activities where liquids can be used” [4]. The main advantage of ionic liquids is that they are a new class of solvents by their non-molecular nature. The ionic liquid environment is very different of that of all molecular polar or non-polar organic solvents [5]. Beside the intrinsic non-molecular nature of ILs giving them unique solvent properties, the major advantages of ILs are their extremely low vapor pressure and their several hundredths degrees liquid range [1–6]. Analytical chemistry and especially chromatography must find practical uses of such solvents. This review will rapidly list the physico-chemical properties of some ionic liquids. Then, their uses in gas chromatography (GC), capillary electrophoresis (CE) and liquid chromatography (LC) will be reviewed. The problem of the IL analysis and quantitation will also be discussed in the review.

15 15 16 16 17 17

possible low temperature melting salts and more than two thousands ILs are known today. Beside their low melting point, they have a wide range of solubility, viscosity or density as illustrated in Table 1 [7,8]. The IL acronyms are also listed in Table 1. ILs were dubbed “designer” solvents since it is almost possible to tailor a particular IL associating an anion with a cation adapted for a specific reaction [5]. The polarity of some ionic liquids is given in Table 1 as the ETN parameter of Reichardt and Harbusch-Gornert [9]. Water has a value of 100 in that scale. Methanol, acetonitrile, acetone and heptane have respectively the decreasing values 77, 47, 36 and 5. Most ILs have ETN values between 50 and 70 or a polarity close to that of ethanol [10]. ILs with nitrate and/or thiocyanate anions seem to have an even higher polarity approaching that of water (Table 1). The extremely low vapor pressure of most ILs is the main reason that renders them useful in green chemistry. In chemical processes, they are easily recyclable and produce minimum pollution by volatile organic compounds if no organic solvent are used to recycle them [5,6]. IL vapor pressure is most often non-measurable at room temperature. Fig. 1 compares the vapor pressure of two ILs, 1-ethyl-3-methyl imidazolium bis(trifluoromethylsulfonyl) amide (EMIM NTfO2 ) (mp −9 ◦ C) and 1-butyl-3-methyl imidazolium dicyanamide (BMIM DCA) (mp −6 ◦ C) with three liquids: mercury (mp −39 ◦ C), the liquid metal used in barometers, nonacosane (C29 H60 , mp 64 ◦ C), the less volatile alkane with full documented data [11] and water as the classical reference liquid. The vapor pressures of the two ILs were determined between 180 and 260 ◦ C [12]. The thermochemical measurements were used to calculate the parameters of the equation for the IL molar enthalpy of vaporization. This equation allows estimating the vapor pressure of the ILs at room temperature [12]. The calculated vapor pressures of

2. Physicochemical properties of ionic liquids The reasons for the low melting point of a particular IL are not clear. It was stated that this characteristic has little to do with any fundamental property of the salts. Selected properties, such as thermal stability and miscibility, mainly depend on the anion, while others, such as viscosity, surface tension and density, depend on the length of the alkyl chain in the cation and/or shape or symmetry [1,5]. The combination of the cited different anions and cations has expanded considerably the number of

7

Fig. 1. Vapor pressure of molecular liquids compared to ionic liquids.

8

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

Table 1 Physicochemical properties of selected ionic liquids sorted by the anion Code

Cation name

m.w. (Da)

Melting point (◦ C)

Density (25 ◦ C)

Refrac. index

Viscosity (25 ◦ C) (cP)

Sol. in water

377 391 405 405

22 −17 14 20

1.559 1.52 1.452 1.495

1.422 1.4231 1.426 1.4305

44 18 35 88

n n

405

−39

1.47

1.4275

37

416 419 419

0 −4 −22

1.44 1.429 1.432

39 80 36

n

1.4271 1.43

419

15

1.46

41

n

422

−50

1.4

71

n

433 578 634 648 690

−8 25.2 −7 −50 11.2

1.404 1.16 1.11 1.1 1.1

1-Ethyl-3-methyl imidazolium 1-Butyl-3-methyl imidazolium N-Butyl-N-methyl pyrrolidinium Triethylhexyl ammonium

177 205 208

−21 −6 −55

1.06 1.06 0.93

252

−43

1-Ethyl-3-methyl imidazolium 1-Butyl-3-methyl imidazolium 1-Butyl-2,3-dimethyl imidazolium 1-Hexyl-3-methyl imidazolium 1-Octyl-3-methyl imidazolium 1-Decyl-3-methyl imidazolium Sodium

197.8 225.8 239.8

6 −82 37

1.248 1.208 1.2

253.8

−82

281.8 309.8

−79 −25

109.8

384

1-Butyl-3-methyl imidazolium 1-Hexyl-3-methyl imidazolium 1-Octyl-3-methyl imidazolium Potassium

284 312

10 −61

1.373 1.304

340 184

−40 575

1.2

1-Ethyl-3-methyl imidazolium 1-Hexyl-3-methyl imidazolium 1-Octyl-3-methyl imidazolium Tetraheptyl ammonium 1-Butyl-3-methyl imidazolium chloride 1-Butyl-3-methyl imidazolium bromide 1-Butyl-3-methyl imidazolium iodide Sodium Sodium Sodium Sodium

146.5 202.5

89 −75

1.12* 1.05

230.5 445.5 174.5

0 −9 65

1 0.882 1.10*

Bis(trifluoromethylsulfonyl) amide MMIM NTfO2 1,3-Dimethyl imidazolium EMIM NTfO2 1-Ethyl-3-methyl imidazolium 1,3-Diethyl imidazolium EEIM NTfO2 1-Ethyl-2,3-dimethyl EM2MIM NTfO2 imidazolium EMM5IM NTfO2 1-Ethyl-3,5-dimethyl imidazolium MPPyr NTfO2 Methylpropyl pyridinium BMIM NTfO2 1-Butyl-3-methyl imidazolium EEMIM NTfO2 1,3-Diethyl-2-methyl imidazolium 1,2-Dimethyl-3-propyl MM2PMIM NTfO2 imidazolium BMPyrrol NTfO2 N-Butyl-N-methyl pyrrolidinium BEIM NTfO2 1-Butyl-3-ethyl imidazolium Tetrapentyl ammonium (C5 )4 N NTfO2 (C6 )4 N NTfO2 Tetrahexyl ammonium MTOA NTfO2 Methyl trioctylammonium Tetraheptyl ammonium (C7 )4 N NTfO2 Dicyanamide EMIM DCA BMIM DCA BMPyrrol DCA C6 (C2 )3 N DCA Tetrafluoroborate EMIM BF4 BMIM BF4 BMMIM BF4 HMIM BF4 OMIM BF4 DMIM BF4 Na BF4 Hexafluorophosphate BMIM PF6 HMIM PF6 OMIM PF6 K PF6 Halogenate EMIM Cl HMIM Cl OMIM Cl (C7 )4 N Cl BMIM Cl BMIM Br BMIM I Na F Na Cl Na Br Na I

1.4285

48 430 435 800 453

64

51 n

21 37 50

s

66 233 780

s s s

1.208

310

p

1.11 1.072

440 930

p

1.429

2,47*

54

1.411

Solid

Solid

400 800

18 g L−1 n

810

n 90 g L−1

Solid 7500

s s

16,000 598 Solid

s s s s

−72

42 58.5 103 150

993 801 747 661

1110 2.56* 2.16* 2.17* 3.66*

67

54 63

s

218.9 265.9

ETN (×100)

s s s s

67

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

9

Table 1 (Continued ) Cation name

m.w.

Melting point (◦ C)

Density (25 ◦ C)

Refrac. index

Viscosity (25 ◦ C) (cP)

Sol. in water

1-Ethyl-3-methyl imidazolium 1,3-Diethyl imidazolium 1-Butyl-3-methyl imidazolium 1-Butyl-3-ethyl imidazolium 1-Hexyl-3-methyl imidazolium 1-Ethyl-3-methyl imidazolium 1-Butyl-3-methyl imidazolium 1-Butyl-3-ethyl imidazolium

260 274 288 302 316

−9 23 16 2 29

1.39 1.33 1.29 1.18 1.20

1.4332 1.4367 1.438 1.441

45 53 90 90 160

s

220 438 452

−65 20 21

1.24 1.473 1.427

Formate (methanoate) EAF Ethyl ammonium PAF Propyl ammonium BAF Butyl ammonium

91 105 119

−10 −10 −10

Acetate (ethanoate) EMIM Act BMIM Act EMIM TFAct

1-Ethyl-3-methyl imidazolium 1-Butyl-3-methyl imidazolium 1-Ethyl-3-methyl imidazolium

170 198 224

−20 −20 −14

Thiocyanate BA SCN secBA SCN DPA SCN EMIM SCN

Butylammonium Sec-butylammonium Dipropylammonium 1-Ethyl-3-methyl imidazolium

132 132 160 169

Nitrate EA NO3 PA NO3 TBA NO3

Ethylammonium Propylammonium Tributylammonium 1-Ethyl-3-methyl imidazolium methylsulfate 1-Butyl-3-methyl imidazolium methyl sulfate Tetrahexylammonium benzoate 1-Ethyl-3-methyl imidazolium methylsulfate 1-Butyl-3-methyl imidazolium methyl sulfate

Code Perfluoroalkylsulfate EMIM TfO EEIM TfO BMIM TfO BEIM TfO HMIM TfO EMIM PFES BMIM PFBS BEIM PFBS

Other anions EMIM MS BMIM MS (C6 )4 N Bzt EMIM AlCl4 BMIM AlCl4

s

ETN (×100)

67

n

99 373 320

s

0.990 0.979 0.973

11.5 18 22.2

s s s

1.03 1.06 1.285

s s

1.4405

91 525 35

20.5 22.5 5.5 −6

0.949 1.013 0.964

1.5264 1.5262 1.5062

97 196 86

s s s

95 101

108 122 248

12.5 4 21.5

1.122 1.157 0.918

1.4537 1.4561 1.4627

32 67 640

s s s

95 92 80

206

5

1.24

80

s

234

−20

1.2

180

s

476

−50

0.938

895

n

280

9

1.3

20

Decompose

308

−10

1.24

26

Decompose

1.4052 1.4025

79 76 74

42

ETN is the Reichardt polarity index (×100 so that ETN water = 100). Density and viscosity values at 25 ◦ C except when an asterisk (*) indicates that the given value corresponds to the salt melting temperature. Solubility in water at room temperature: n = non-soluble (two phases form); s = soluble; p = partly soluble. TfO = triflate anion or trifluoromethyl sulfate; PFES = perfluoroethyl sulfate; PFBS = perfluorobutyl sulfate; TFAct = trifluoroacetate or trifluoro ethanoate anion. Data selected from ref. [1–3,6–8].

EMIM NTfO2 and BMIM DCA at room temperature (25 ◦ C) are respectively 12 and 2 ␮Pa. For comparison, the corresponding vapor pressure of water, mercury and nonacosane are respectively 2500, 0.27 and 0.01 Pa. To illustrate the volatility of the liquids, it is interesting to calculate the volume of gas (P = 1 atm) needed to evaporate 1 mg of liquid at 25 ◦ C. 50 mL of dry gas will evaporate 1 mg of water at 25 ◦ C. This volume becomes 43 L for mercury, 560 L for nonacosane (a calculated value since nonacosane is solid at room temperature) and 600,000 L or 600 m3 for EMIM TfO2 and 5.6 billion L or 5600 m3 for BMIM DCA. These examples clearly show the remarkably low volatility of ILs. It also shows that two ILs may have widely differing volatilities and/or volatility behavior. In our example, BMIM DCA is ten times more volatile than EMIM TfO2 at 200 ◦ C (Fig. 1) and

six times less volatile at 25 ◦ C. It was recently demonstrated that some aprotic ILs could be distilled under reduced pressure at 200–300 ◦ C [13]. The extremely low volatility of ILs renders them little flammable so they could candidate to replace organic pollutant solvents [14,15]. ILs were quickly considered as benign or green solvents when full toxicity studies are not completed. It seems that many ILs have a significant ecotoxicity [16]. For example, the slow hydrolysis of the hexafluorophosphate anions released in water produces free toxic fluoride anions [17]. The other physico-chemical properties of ILs, not listed in Table 1 because too few data were found and however very important when the IL is used in separation science, include (i) their electrical conductivity which is important when ILs are

10

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

used as electrolytes in CE, (ii) their viscosity and surface tension that are related to their coating properties in GC, (iii) their absorbance spectrum in UV that is important to detect them, and (iv) their solubility in non-aqueous solvent and solvating properties and ability to dissolve compounds, important properties in liquid extraction and headspace preconcentration [18]. The purity of a particular IL is very linked to its physico-chemical properties. For example, trace amounts of chloride ion impurities were found to change the BMIM PF6 viscosity drastically [6,10]. 3. Gas chromatography and ionic liquids The low volatility and thermal stability of IL makes them ideal candidates for GC stationary phases. The association of ILs and GC has a great interest in chemical separation. It was also used to measure physicochemical parameters and to quantify solute–IL interactions [7]. 3.1. Classical coated stationary phases The GC stationary phase material is classically deposited on support particles, mainly silica particles, that will packed in relatively short columns (few meters). It can also be coated on the internal wall of capillary columns (50–200 ␮m i.d. silica tubing) or macrobore columns (530 ␮m i.d. silica tubing) that can be as long as 30 m. ILs were mainly used in capillary columns but there is no objection to use them in packed columns. The use of salts as stationary phases in GC was reported as early as 1959 by Barber et al. [19]. He used stearates of divalent cations such as manganese, cobalt, nickel, copper and zinc to separate alcohols, amines and ketones with a low but acceptable efficiency at the time. Later, Poole and coworkers examined the stationary phase characteristics of early ILs such as ethylammonium nitrate [20] and ethylpyridinium bromide [21]. The columns showed an interesting selectivity for polar and H-bond capable solutes, but they had a low efficiency and the results were not acceptable for non-polar solutes with columns degrading above 170 ◦ C [20,21]. Imidazolium-based ILs showed a better efficiency and confirmed the very different selectivities obtained with polar and non-polar solutes [22]. BMIM TfO and methoxyphenyl MIM TfO ILs were tested as GC stationary phase with elevated thermal stability and good film forming capability [23]. Fig. 2 compare the separation of polychlorinated biphenyls (PCBs) on a 10-m 1-methyl-3-(4-methoxyphenyl) imidazolium triflate capillary column and on a 10-m commercial DB-17 (50% phenyl dimethyl polysiloxane) column. With exactly the same temperature program, the separation is 4 min (30%) faster with the IL column (Fig. 2A). The observed selectivity is very similar, being even better on the IL column with the closely related 2,3 - and 2,4 -dichloro biphenyls (peaks 5 and 6 in Fig. 2). Capillary GC columns containing coated IL stationary phases could work up to temperatures approaching the 300 ◦ C mark [22,23]. 3.2. Special ionic liquid-based gas chromatography stationary phases Recently new dicationic ILs showed a thermal stability reaching 400 ◦ C [24]. PAHs and PCBs could be separated on a

Fig. 2. Separation of PCBs on (A) a 10-m 1-methyl-3-(4-methoxyphenyl) imidazolium triflate capillary column and (B) a 10-m DB-17 commercial capillary column. Temperature program: 155 ◦ C for 3 min next 3 ◦ C/ min to 200 ◦ C. Solutes: (1) solvent hexane; (2) biphenyl; (3) chlorobiphenyl; (4) 2,2 -dichlorobiphenyl; (5) 2,3 -dichlorobiphenyl; (6) 2,4 -dichlorobiphenyl; (7) 2,2 ,6-trichlorobiphenyl; (8) 2,2 ,3-trichlorobiphenyl; (9) 2,2 ,4,4 tetrachlorobiphenyl; (10) 2,2 ,4,4 ,6,6 -hexachlorobiphenyl. Adapted from Ref. [23].

capillary column coated with a cross-linked dicationic IL using gradient temperatures reaching 335 ◦ C with little column bleed [25]. These IL-based stationary phase also presented a very different selectivity for the polar compounds and for the apolar one. It is almost possible to consider a IL-based capillary column as a polar column for polar compounds and, at the same time, as an apolar column dedicated to apolar compounds [22–25]. The IL solvent properties were used to prepare GC capillary columns coated with an IL containing cyclodextrins (CDs) as chiral selectors. BMIM Cl was found suitable to dissolve diand/or per-methylated CDs [26]. However, it was demonstrated that the chiral cavity of the CDs was occupied by the IL imidazolium ring, blocking it for solute–CD inclusion complexation. The external part of the CD was still able to give partial enantioselectivity with selected enantiomeric pairs [26]. Chiral ILs were soon developed to prepare chiral GC capillary columns [27]. Ephedrinium ILs were able to resolve the enantiomers of a variety of chiral alcohols, diols, sulfoxides, epoxides and acetylated amines. GC has been also a widely employed tool for determining thermodynamic properties of ILs [28–31]. ILs are often used as new solvents in sample preconcentration or treatment. ILs were used as solvents in headspace GC [18] and coated bars used in solid phase microextraction followed by GC analyses [32,33]. They are promising phases in GC-2D [34,35]. 4. Liquid chromatography and ionic liquids Liquid chromatography is defined as a separation method using a liquid mobile phase. The liquid mobile phase can be a pure solvent or, most often, a mixture of different solvents. The very low volatility of ILs may not be of critical importance in LC.

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

The non-molecular nature of ILs could give original selectivities or solubility properties that should be evaluated. 4.1. Ionic liquids as reversed-phase liquid chromatography organic modifiers The main problem in considering IL as possible organic modifiers in RPLC is their very high viscosity (Table 1) at least one order of magnitude higher than that of methanol or acetonitrile, the two most employed RPLC organic modifiers. The less viscous ILs in Table 1 are the monoalkylammonium nitrate, formate or acetate with viscosities at room temperature still higher than 10 cP. Poole et al. were the first to use ILs as mobile phase in RPLC as soon as 1987 [36]. They separated some aromatic test solutes working with a 1 mm i.d. column filled with 10 ␮m C18 particles and a 0.05 mL/min flow rate [36]. Even with these experimental conditions, the back pressure was extremely high. Thiocyanate ILs corroded rapidly the metallic parts of the HPLC system and their use had to be discontinued [36]. Waichigo et al. used alkylammonium RTILs as solvent in water-IL mobile phases with classical C18 or polystyrenedivinylbenzene RPLC stationary phases [37–39]. They demonstrated that different compositions of alkylammonium acetate or formate, between 20 and 60% (w/v), with water could separate selected test aromatic solutes. The chromatograms obtained approached those achieved with methanol or acetonitrile mobile phases and the same columns. Fig. 3 compares the separation of a vitamin mixture on the same PRP-1 15-cm column. Fig. 3A

Fig. 3. Separation of water-soluble vitamins on a 15-cm polystryrene divinylbenzene PRP-1 column (5 ␮m particle, 4 mm i.d.). (A) Mobile phase 20% (v/v) ethylammonium formate–80% 0.02 M acetate buffer pH 6.4, 1 mL/min. (B) mobile phase 20% methanol–80% 0.02 M acetate buffer pH 6.4, 1 mL/min. Solutes: (1) ascorbic acid (vitamin C); (2) nicotinic acid (vitamin PP); (3) thiamine (vitamin B1); (4) pyridoxine (vitamin B6); (5) niacinamide (vitamin B3). Detection UV 254 nm. Adapted from Ref. [37].

11

is the chromatogram obtained with an IL containing mobile phase. Fig. 3B is the chromatogram obtained with a classical methanol/water mobile phase. The retention order is the same. The analysis duration is slightly shorter with the classical mobile phase. The efficiency is comparable, the plate numbers counted with the classical mobile phase are 20% higher than that counted with the IL mobile phase. The major difference is not seen in Fig. 3: it was with the experimental back pressure that was twice higher (11 MPa or 1.6 kpsi) with the IL mobile phase at 1 mL/min and room temperature than with the classical methanol/water mobile phase. All published works demonstrated that the studied particular alkylammonium salts were inferior to the classical RPLC methanol or acetonitrile solvents in that they had inferior UV transparency, dramatically higher viscosity producing high pressure drops, and inferior peak efficiencies. They also had somewhat lower elution strength at similar concentrations [36–39]. Since these ILs have clearly inferior chromatographic capabilities being as polluting as methanol or acetonitrile when released in the environment, since they are also much more costly, they do not have, at the moment, any future as possible organic modifier replacements in RPLC. Considering that most ILs listed in Table 1 have an even higher viscosity than the studied alkylammonium ILs, it is unlikely that any ILs will ever replace methanol and/or acetonitrile as organic modifiers in routine RPLC. 4.2. Ionic liquids as mobile phase additives Basic compounds are difficult to separate in RPLC on silicabased stationary phases due to interaction between the cationic sites of the compounds with anionic silanols of the stationary phase. These interactions produce peak tailing and lengthy retention of the basic compounds. Amines or divalent cations were demonstrated to be useful silanol-blocking agents [40–42]. Jiang proposed to add selected ILs as silanol screening agents in totally aqueous mobile phases in the separation of ephedrines [43] and catecholamines [44]. The addition of 2–50 mM IL to aqueous mobile phases did improve the basic compound peak shapes. However, these improvements were associated with changes in retention factors. A wide variety of ILs was investigated [45] and a model involving ion-pairing and a layer of IL adsorbed on the C18 surface was proposed [45]. Kaliszan et al. confirmed the significant improvement on basic compound peak shape obtained adding small amounts of ILs to mobile phases [46,47]. The ILs had a better silanol blocking activity than classical ternary amines [48,49]. However, they also observed that peak shape improvements were associated with significant changes in retention factors. Depending on the IL used, the retention factors could increase or decrease [47–49]. When added as additives in low concentrations in aqueous solutions, ILs become just regular salts. Their specific properties: a low melting point, a high thermal stability and an extremely low vapor pressure are lost and/or not important. As salts, ILs have a dual nature that should never be forgotten: they are obviously made by cations associated with an equal amount of anions. Both species can affect the chromatographic

12

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

results. The inclusive effect of the two oppositely charged ions may be synergistic or antagonist [50]. It was demonstrated that anions could adsorb on hydrophobic stationary phase in amount depending on the Hofmeister anion series [51,52]:

effect decreases the polar character of the imipramine cation. The ion-pair is more retained by the C18 stationary phase. If NaCl is replaced by the BMIM Cl IL, a 30% decrease in retention factor is observed associated with a dramatic peak shape enhancement.

25 ␮mol, 10 ␮mol and only less than 1 ␮mol of hexafluorophosphate, tetrafluoroborate and chloride anions were respectively adsorbed on a Kromasil C18 stationary phase when 30 mM solution of the corresponding sodium salts were present in the acetonitrile/water 30/70% (v/v) mobile phase [50]. Similarly, IL cations also can adsorb on C18 stationary phases following a lyotropic series directly related to alkyl chain lengths. 40 ␮mol, 80 ␮mol, 200 ␮mol and 500 ␮mol of 1-ethyl-, 1-butyl-, 1-hexyl- and 1-octyl-3-methylimidazolium cations were respectively adsorbed on the Kromasil C18 stationary phase when 30 mM of the corresponding hexafluorophosphate ILs were present in the acetonitrile/water 30/70% (v/v) mobile phase [50]. Obviously, the later adsorption quantities cumulate the synergistic effect of the PF6 − anion with the cation lyotropy. In other words, the major part of the 40 ␮mol adsorbed EMIM PF6 is due to PF6 − anion adsorption. The major part of the adsorbed 500 ␮mol of OMIM PF6 is due to C8 (OMIM cation)–C18 chain (stationary phase) hydrophobic interaction. Basic compounds most often bear amine groups positively charged in low pH mobile phases. Consequently they are necessarily retained by a combination of electrical (charge–charge) and hydrophobic interactions with the stationary phase and with the ions of the mobile phase. The mixed mechanism involves ion-pairing, ion-exchange and hydrophobic partitioning. The basic compound peak position depends on the overall strength of combined solute–stationary phase interactions. The basic compound peak shape depends on the kinetics of the interaction. In aqueous mobile phases, charge–charge interactions are usually stronger and slower than hydrophobic interactions. Table 2 lists all ion-mobile and ion-stationary phase possible effects on both interactions and the resulting effect on the chromatograms. Fig. 4 illustrates the effects in the case of a mixture of basic compounds. Focusing on the imipramine peak, the replacement of 0.01 M NaCl by 0.01 M NaBF4 in the mobile phase produces a doubling of the retention factor associated to a small improvement of the peak shape. The BF4 − anions adsorb on the C18 stationary phase and associate with the imipramine cation. The first effect increases the negative charge of the stationary phase increasing the retention factor of all positively charged solute. The second

In this situation, the BMIM+ cation adsorbs on the C18 stationary phase without associating with the imipramine solute. Charge–charge repulsion occurs between the BMIM covered stationary phase and imipramine; the retention factor is lower, the peak shape is better imipramine being mainly retained by hydrophobic fast interactions. Fig. 4 bottom chromatogram is obtained with 0.01 M BMIM BF4 IL in the mobile phase. In that case, the two IL ions adsorb on the C18 surface and the chaotropic BF4 − anion can associate with the imipramine cation forming less polar ion-pairs. Consequently, the imipramine retention factor is increased as well as the peak shape since fast hydrophobic interactions are mostly involved in the retention mechanism of the ion-pair. The studied Fig. 4 mixture contained o-toluidine that was in a molecular state in the experimental conditions (pKa = 4). As such, o-toluidine is not sensitive to charges on the stationary phase and cannot form any ion-pair association with mobile phase ions. Its peak is not sensitive to the mobile phase salts as shown by the vertical dotted line in Fig. 4, confirming the ion-pairing, ion-exchange, hydrophobic mixed mechanism for cationic solutes. The recently proposed separation of adrenergic amines [53] or beta-blockers [54] with mobile phase containing IL additives obeyed the mixed mechanism as well as the previously proposed works [43–48,55]. In conclusion of the use of ILs as efficient silanol screening agents in the separation of basic compounds, it can be said that there is no “best” IL. If the basic compounds are polar and lightly retained, a polar IL additive with a strongly chaotropic anion such as MMIM PF6 , EMIM PF6 or EMIM ClO4 is recommended. With less polar and hydrophobic amines, a less polar IL additive with a cosmotropic anion such as BMIM Cl or HMIM Cl is likely a good choice. ILs as silanol screening agents may be considered as “green” additives in that they allow for peak shape improvement and reduced retention without increasing the mobile phase organic modifier content [47,54]. However, ILs are certainly not the additive of choice with a MS detector. The non-volatility of ILs will be responsible for IL condensation and pollution in the electron-spray or atmospheric pressureionization sources.

Table 2 Possible interactions of the IL ions in the case of basic compounds (positively charged) Interactions in

IL anion−

IL cation+

Mobile phase

Ion-pairing with solute+ Decreases electrostatic interaction = better solute peak shape, increases hydrophobic interaction = higher solute k Anion adsorption increases ion-exchange interaction with cationic solute = higher solute k and little effect on peak shape

Repulsion with solute+ May interact with the anion associated with the solute

Stationary phase

Cation adsorption decreases charge–charge interaction with cationic solute, silanol screening = lower solute k and better peak shape

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

13

on silica particle in order to obtain an imidazolium anion exchange stationary phase [57]. 1-Methyl- and imidazole anion exchange stationary phases were able to separate up to 11 different anions in one run [58]. More work is needed to obtain peak efficiencies comparable to those given by long term established ion-exchange composite stationary phases. Stalcup et al. prepared a butylimidazolium bromide stationary phase via hydrosilylation of the alkenylbromide followed by immobilization of the silane on 5 ␮m Nucleosil particle. The obtained column was used to separate a variety of solutes wide enough to make linear solvation energy relationship studies [59]. It was found that the 1-butyl-3-heptylimidazolium bromide stationary phase was similar to conventional phenyl-based stationary phases under reversed-phase conditions for the separation of a group of neutral aromatic solutes. More recently, two new stationary phases based on PMIM Br and BMIM Br ILs were studied for the separation of a group of organic acids [60]. The hydrophobic interactions and ion-exchange seemed to be the major factors that contributed to the retention. One of the main advantages of the use of surface-immobilized IL stationary phases is that effective separations are achieved with aqueous mobile phases without organic solvent or containing very small amounts of the solvent (∼1%). 4.4. Use of ionic liquids in counter-current chromatography

Fig. 4. Effect of selected additives on the separation of five basic compounds. Column: Kromasil C18 15 cm, 4.6 mm i.d.; mobile phase: acetonitrile/water 30/70% (v/v) pH 4 with 10 mM ammonium acetate plus the mentioned salt additive, 1 mL/min. Retention factor, k, peak efficiency, N, and asymmetry, As, indicated for the last eluted compound: imipramine. The vertical dotted line covers the o-toluidine peak not affected by the salt additions. Detection UV 254 nm. Retention times in min. Data and figures adapted from Ref. [50].

4.3. Ionic liquids as liquid chromatography stationary phases Considering the effect of ILs added to the mobile phase in RPLC, it was soon thought that IL stationary phases should be evaluated. Jiang et al. confined a vinyl-hexylimidazolium tetrafluorobarate IL at the surface of porous silica particles activated with a silane-coupling agent (mercaptopropyl trimethoxyxilane). The IL-bonded silica particles were packed in a 15-cm 4.6 mm i.d. column tested with methanol/water mobile phases to separate an ephedrine mixture [56]. The results were not as good as those obtained using IL as additives with a commercial column [43]. Later, they bound 1-methylimidazole

Another chromatographic technique where RTILs have found application is counter-current chromatography (CCC). In CCC, the mobile and stationary phases are two immiscible liquids; the liquid stationary phase being maintained in place inside the column by centrifugal fields [61]. RTILs may form biphasic liquid systems with numerous solvents, including water, which makes them possible candidates in CCC [62]. However, very little work has been reported on the use of RTILs in CCC. Application of BMIM PF6 in CCC was investigated for a group of 38 aromatic derivatives with different acid–base behavior [63]. A previous report had explored the possibilities of the BMIM PF6 –water system in the separation of a large variety of compounds with different functionalities [10]. Due to the high viscosity of BMIM PF6 , acetonitrile was added with a final selected composition of 40/20/40 (v/v) water/acetonitrile/BMIM PF6 biphasic liquid system. The fully water-soluble IL BMIM Cl is able to form two immiscible aqueous phases when dibasic potassium phosphate (K2 HPO4 ) is added to the solution [64]. The aqueous two phase system (ATPS) based on BMIM Cl, K2 HPO4 and water was tested in CCC and compared with the classical ATPS made by polyethylene glycol (PEG) with an average molecular mass of 1000, K2 HPO4 and water in terms of polarity, density and ability to separate a group of polar proteins [65]. The discrimination factor of the ionic liquid system and its intrinsic hydrophobicity were respectively found 3 times higher and 10 times lower than the respective values of the PEG 1000 ATPS. It was found that the BMIM Cl/phosphate ATPS could be used to extract short chain alcohols (e.g. ethanol) in the IL-rich aqueous phase [65].

14

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

5. Ionic liquids in capillary electrophoresis Capillary electrophoresis (CE) makes use of support electrolytes that are salts. Since ILs are viscous conductive salts, they may not be directly used as solvent in capillaries: the current would be high and/or the applied voltage and electric field would be low. ILs could be used as capillary wall coating as in GC. They are also possible candidates as running electrolytes in aqueous solutions or in polar organic solvents (non-aqueous capillary electrophoresis, NACE). Modified ILs were used to perform chiral and micellar electrokinetic chromatography (MEKC) separations. 5.1. Ionic liquids as capillary wall covalent coating ILs were used to reduce interaction between analytes and the capillary wall. The first attempt was done by Qin and Li that covalently bonded propyl methyl imidazolium chloride (PMIM Cl) to a silica capillary [66]. They were able to separate sildefanil (Viagra) from its metabolites and to use mass spectrometry as the detector. They observed a reversal of the electroosmotic flow (EOF) due to the positive character of the bonded PMIM moieties [66]. Using similarly modified capillaries, DNA fragments [67] and alkyl phosphonic acids and esters [68] were separated. Cations were successfully separated with IL bonded capillaries [69,70]. However, the separation also required ILs added in the background electrolyte mixture which precluded MS detection. 5.2. Ionic liquids as background electrolyte and dynamic wall coating in aqueous capillary electrophoresis ILs are electrolytes that can be used as background electrolytes in CE. The hydrophobic character of their cationic part is responsible for a significant adsorption on the capillary wall. The immobilized adsorbed IL cations produce a change in the EOF direction that can be used for separations. Since the hydrophobicity of the IL cation strongly depends on its alkyl chain length, the dynamic wall coating can be adjusted at will playing with the nature of the IL cation and with its concentration [66,67,69,70]. Stalcup and coworkers [71] analyzed the polyphenolic compounds found in grape seed extracts by employing different 1,3-dialkylimidazolium ionic liquids. A mechanism based on dynamic wall coating and the association between the free imidazolium cations and the polyphenols was proposed. They also reported the separation of monohalogenated phenols in the presence of EMIM BF4 and compared the results with those obtained with TEA BF4 electrolytes [72]. In both cases, increased halogen size correlated with increased affinity for the electrolyte cation. The dynamic IL coating is very easy and it has been widely employed. Jiang et al. dynamically coated capillary with imidazolium-based RTILs to separate basic proteins, such as lysozyme, cytochrome C, trypsinogen and ␣-chymotrypsinogen [73]. Baseline separations, high efficiencies and symmetrical peaks were obtained. Laamanen et al. developed two CE methods based on aqueous phosphate running buffers with tetradecyltrimethylammonium bromide and the IL

dimethyldinonylammonium bromide as modifiers for the separation of eight carboxylates [74]. Better separation was achieved when the IL was present as the flow modifier. Other applications were reported by Qi et al. which used the ionic liquid BMIM BF 4 for the determination of five anthraquinones in Chinese herbs [75]. ␤-Cyclodextrin was also added as a modifier. Further investigation by the same group developed novel CE methods which used EMIM BF4 and BMIM BF4 to separate and determine some bioactive flavone derivatives [76] or again, anthraquinones [77], in similar samples. Flavonoids [78] and nicotinic acids and related compounds [79] were also separated. 5.3. Ionic liquids as background electrolytes in non-aqueous capillary electrophoresis In NACE, the CE liquid phase is much less polar than water. The dynamic coating of the capillary wall is greatly decreased and/or inexistent. The EOF direction is not changed by IL additions and the solute/IL interaction is the main mechanism responsible for enhanced separation. Vaher et al. were the first to use ILs in NACE working with pure acetonitrile to separate water-insoluble dyes [80]. Similar non-aqueous systems with various types of RTILs with different anions and cations were reported by the same authors for separation of phenols and aromatic acids [81] and polyphenols [82]. Significant changes in the electrophoretic mobility of the system were observed and attributed to the anionic part of the RTIL. The interactions of ILs and chiral propionic acid derivatives (the analgesic and anti-inflamatory “profen” compounds) were fully studied in NACE with acetonitrile–alcohol mixtures showing a significant interaction of the IL with the capillary wall [83]. 5.4. Use of chiral ionic liquids The analgesic compounds separated with acetonitrile– alcohol electrolyte solution in [83] were chiral compounds. The two enantiomers of a chiral pairs could be separated using chiral ionic liquids. Chiral ionic liquid based on quaternary ammonium were synthesized [84]. All NACE experiments with the chiral ILs were unsuccessful. Some enantioselectivity for the “profen” enantiomers was obtained working with running buffers containing water and associating the chiral ILs with cyclodextrins [84]. A chiral IL based on a quaternary aminobutanol derivative showed some capability to resolve amino acid enantiomers with aqueous electrolyte phases [85]. More work is needed to obtain reliable chiral selectors based on ILs. 5.5. Micellar electrokinetic chromatography with ionic liquids If the alkyl tail of the IL cation is long enough, micelles can be formed in aqueous medium. Such RTILs were used to perform MEKC for the separation of two achiral mixtures (alkyl aryl ketones) and one chiral mixture (binaphthyl derivatives)

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

[86]. Polymeric surfactants and several alkyl imidazolium ILs were investigated. The authors established that the polymeric surfactant controlled the separation selectivity when the IL influenced greatly the separation duration and peak efficiency [86]. Two amino acid-derived (leucinol and N-methylpyrrolidinol) chiral ionic liquids were synthesized and used as pseudostationary phase in MEKC [87]. The chiral separation of two acidic analytes ((±)-␣-bromophenylacetic acid and (±)-2-(2chlorophenoxy)propanoic acid) was strongly dependent on the presence of opposite charge and the structural compatibility between chiral selector and the analyte. BMIM BF4 was also reported as an effective modifier in MEKC with sodium dodecyl sulfate (SDS) micelles for the separation of lignans found in medicinal herbs [88]. Fig. 5 shows that the addition of as little as 0.01 M BMIM BF4 to the SDS containing running buffer completely changed the observed peak position and width resulting in the complete separation of the lignan mixture evaluated. It is speculated that the BMIM+ cation modifies the SDS micelles changing the micellar solute partitioning. This explanation is plausible since the EOF is not significantly modified by the IL addition (Fig. 5), however the possible effect of the BF4 − lyotropy is ignored. The same authors also employed BMIM BF4 in microemulsion electroki-

Fig. 5. Electropherograms of a standard mixture of lignans: (1) schisandrin; (2) schisantherin; (3) deoxyschisandrin; (4) ␥-schisandrin. Running buffer (A): 5 mM borate, 5 mM phosphate, 20 mM SDS, pH 9.2, I = 29 ␮A; (B): same buffer + 10 mM BMIM BF4 , I = 38 ␮A. Uncoated 60 cm, 50 ␮m i.d. fused silica capillary; 25 kV; 23.5 ◦ C; UV detection 254 nm. Adapted from Ref. [88].

15

netic chromatography in a system containing ethyl acetate, SDS and butanol for the analysis of three flavones in medicinal preparations [89]. 6. Separation methods for ionic liquid analysis With the exponentially raising use of ILs in many fields of chemistry, reliable methods are needed for their analysis and control. 6.1. Reversed-phase liquid chromatography of ionic liquids RPLC was the simplest and preferred technique involving C18 , C8 or short chain bonded silica stationary phases. The first separation of eleven 1-alkyl and 1-aryl-3-methylimidazolium RTILs was reported by Stepnowski et al. using RPLC with electrospray ionization mass detection [90]. It was found that the different anions in the selected ionic liquids did not affect the chromatographic behavior of the same cation. It is pointed out that the proposed method used an aqueous–organic mobile phase buffered with 0.02 M ammonium acetate. The method was validated through the analysis of biological samples used in cytotoxicity studies of a known micromolar concentration of the ionic liquid AMIM PF6 (A for amyl or pentyl). In a recent work, we demonstrated the need to consider the dual nature of IL: an anion associated to a cation [91]. The RPLC separation of ILs involves the combination of three mechanisms: (i) hydrophobic interaction, (ii) ion-pairing and (iii) ion-exchange. By changing the experimental conditions, it is possible to exhale one or the other of these mechanisms. Working with a salt-free mobile phase to limit ion-exchanges, it was possible to separate three ILs differing by the anion (Fig. 6A). The elution order depends on the lyotropy of the anions. Injecting an equimolar amount of NaPF6 and BMIM Cl give the same chromatogram as injecting an equal amount of NaCl and BMIM PF6 [91]. When a salt, e.g. sodium chloride, or a buffer, e.g. sodium phosphate, is added to the mobile phase, only ILs differing by the cation can be separated (Fig. 6B). Different ILs sharing the same cation elute in a single peak corresponding to the cation associated with the mobile phase anion. The mixed retention mechanism invariably produces poor peak shapes (Fig. 6). NaPF6 or NaClO4 are a good mobile phase additives to enhance IL peak shape. These chaotropic anions adsorb on the stationary phase and form ion-pairs with the IL cations. The peak shape is improved but the retention factors are increased. A higher organic modifier content (or a gradient elution) may be needed [92]. Different original RPLC stationary phases were tested for IL separation [93–95]. Cholesterol ligands bonded chemically to silica and mixed stationary phases (SG-MIX) containing cyanopropyl, aminopropyl, phenyl, octyl and octadecyl ligands, as well as two commercial octadecyl monolith and butyl packings were tested and compared by Buszewski et al. [93,94]. The butyl and silica monolith with bonded octadecyl groups yielded the best results, probably due to the lowest heterogeneity of these ligands in comparison to the other stationary phases tested [93]. The effect of the polarity of the same group of stationary

16

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

Fig. 6. RPLC separation of ionic liquids. (A) Separation of three BMIM ILs; continuous line: UV 254 nm detection; dotted line: conductimetric detection; salt-free mobile phase: acetonitrile/water 10/90% (v/v), 1 mL/min. (B) Separation of EMIM Cl, BMIM BF4 , HMIM BF4 and OMIM PF6 ; mobile phase: acetonitrile/water 0.01 M NaCl 30/70% (v/v), 1 mL/min; UV detection 254 nm; column Kromasil C18 150 mm × 4.6 mm i.d. Adapted from Ref. [91]

phases in the separation of IL cation mixtures was also evaluated [94]. It was concluded that the retention mechanism was based on dispersive, charge–charge and ␲–␲ interactions. In another work, an ether-linked phenyl stationary phase with polar endcapping was investigated in order to take advantage of the potential ␲–␲ interactions offered by the aromatic system in the imidazolium ring of an IL cation in the separation of imidazolium and pyridinium ILs [95]. Methanol and acetonitrile were used as polar eluents but it was observed that the latter suppressed most available ␲–␲ interactions. On the other hand, the retention of arylated and alkylated ILs did not differ very much probably due to the participation of only one of the solute aromatic moieties in this type of interaction [95]. 6.2. Analytical methods for ion determination ILs are salts, so methods for ion analysis should be able to analyze them. Ion chromatography and capillary electrophoresis were tested for IL analysis. Stuff used ion chromatography to analyze ILs with satisfactory results as soon as 1991 [96]. More recently, Stepnowski et al. used a strong cation-exchange column that was found efficient with a relatively high buffer

concentration (40 mM KH2 PO4 ) [97]. Ion chromatography is recommended for polar ILs with less than six methylene groups in the cation. Less polar ILs, with longer alkyl chains, are better analyzed by RPLC [97]. Very recently, a hydrophilic interaction LC (HILIC) method was proposed to quantitate ILs with a Nucleosil diol column and >90% acetonitrile mobile phases [98]. The very different mode of retention by HILIC produces an order of elution opposite to the usual RPLC order of retention: the hydrophobic OMIM IL elutes first, the EMIM IL elutes last. Limits of detection were about 0.5 injected nmoles [98]. The use of electrophoretic techniques for IL monitoring has been less frequent. A group of 1-alkyl-3-methylimidazolium entities, including isomers and related imidazole derivatives was carried out by CE [99]. Under the studied conditions (running buffer of triethylamine in acidic conditions and added ␣-cyclodextrin) all compounds were separated in less than 8 min. The method was also applied to the detection of impurities in commercial RTILs. Standard mixtures of selected imidazolium cations were also separated by CE with citrate buffer as background electrolyte [100]. More than chromatographic methods, CE has been selected for monitoring and quantification of halide impurities in RTILs [101,102]. A recent review lists most IL determination methods [3]. A word should be said on IL detection after separation. The most popular ILs contain an imidazolium ring that is also a UV chromophore. Conductimeters are also obvious detectors for IL ions as long as the mobile phase does not contain buffer salts that would give too high background conductivity [91,92]. Mass spectrometry was used as a detector for trace amounts of IL [90]. The low volatility of the ILs should be kept in mind when working with a MS detector. Non-volatile ILs are likely to pollute MS ionization sources. 7. Conclusion Ionic liquids are non-molecular solvents with a nonmeasurable vapor pressure at room temperature. They found applications in many fields of the chemical world. ILs can make extremely useful GC stationary phases of original polarity. They have a very good selectivity towards polar as well apolar compounds. ILs have a significant viscosity. So they may not be the best organic modifiers possible in RPLC. However, they found important application as silanol-screening agents in improving the RPLC analysis of basic compounds. Added in low amounts in aqueous mobile phases, it should never be forgotten that ILs are salts made of anions and cations. The differences in cation alkyl chain lengths render obvious the differences in cation hydrophobicity. However, the chaotropic character of many anions found in ILs is too often overlooked: a hexafluorophosphate salt is different from its chloride counterpart. As salts, ILs cannot have a simple retention mechanism in RPLC or CE. Mixed mechanisms involving ion-pairing, ion-exchange and hydrophobic interaction combine to produce retention of the anions and, may be differently, of the cation. For separation and determination of ILs, RPLC has been the preferred technique. All the analyzed IL cations exhibited a

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

reversed-phase behavior that is not affected by the IL anion when buffered mobile phases were employed. The study of different column packings offers the possibility to determine different retention mechanisms in order to improve the analysis and control of ILs. Acknowledgements M.J.R.-A. thanks the Ministerio de Educaci´on y Ciencia from Spain for a Ram´on y Cajal contract at the Universidad de Valencia and financial support by Project CTQ2004-02760/BQU. S.C.-B. thanks the Spanish Project GV 05/124 of the Generalitat Valenciana, Universidad Jaume I. A.B. thanks the Centre National de la Recherche Scientifique, CNRS UMR5180Lanteri, for continuous financial support. References [1] [2] [3] [4] [5]

[6]

[7] [8] [9] [10] [11] [12] [13]

[14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30]

T. Welton, Chem. Rev. 99 (1999) 2071. J. Liu, J.A. J¨onsson, G. Jiang, Trends Anal. Chem. 24 (2005) 20. P. Stepnowski, Int. J. Mol. Sci. 7 (2006) 497. M. Freemantle, C&EN Jan. 1 (2007) 23. G. Fitzwater, W. Geissler, R. Moulton, N.V. Plechkowa, A. Robertson, K.R. Seddon, J. Swindall, K. Wan Joo, Ionic liquids: sources of innovation, Report Q002, QUILL, Belfast, 2005. R.D. Rogers, K.R. Seddon, Ionic liquids, ACS Symposium Series No. 818, American Chemical Society, Washington, DC, 2002.; R.D. Rogers, K.R. Seddon, Ionic liquids, ACS Symposium Series No. 856, American Chemical Society, Washington, DC, 2003.; R.D. Rogers, K.R. Seddon, Ionic liquids, ACS Symposium Series No. 902, American Chemical Society, Washington, DC, 2005. C.F. Poole, J. Chromatogr. A 1037 (2004) 49. Ionic Liquid Chart, Sigma–Aldrich–Fluka, 2005. C. Reichardt, E. Harbusch-Gornert, J. Liebigs Ann. Chem. (1983) 721. S. Carda-Broch, A. Berthod, D.W. Armstrong, Anal. Bioanal. Chem. 375 (2004) 191. V. Emel’yanenko, S.P. Verevkin, A. Heintz, J. Am. Chem. Soc. 129 (2007) 3930. D.R. Lide (Ed.), Handbook of Chemistry and Physics, 79th ed., CRC Press, Boca Raton, FL, 1999. M.J. Earle, J.M. Esperanc¸a, M.A. Gilea, J.N. Canongia-Lopes, L.P.N. Rebelo, J.W. Magee, K.R. Seddon, J.A. Widegren, Nature 439 (2006) 831. P. Wassercheid, W. Keim, Angew. Chem. Int. Ed. 39 (2000) 3772. Y. Chauvin, H. Olivier-Bourbigou, Chemtechnology 25 (1995) 26. D. Zhao, Y. Liao, Z. Zhang, Clean 35 (2007) 42. R.P. Swatloski, J.D. Holbrey, R.D. Rogers, Green Chem. 5 (2003) 361. M. Andre, J. Loidl, G. laus, H. Schottenberger, G. Bentiviglio, K. Wurst, K.H. Ongania, Anal. Chem. 77 (2005) 702. D.W. Barber, C.S.G. Phillips, G.F. Tusa, A. Verdin, J. Chem. Soc. (1959) 18. F. Pacholec, H.T. Butler, C.F. Poole, Anal. Chem. 54 (1982) 1938. F. Pacholec, C.F. Poole, Chromatographia 17 (1983) 370. D.W. Armstrong, L. He, Y. Liu, Anal. Chem. 71 (1999) 3872. J.L. Anderson, D.W. Armstrong, Anal. Chem. 75 (2003) 4851. J.L. Anderson, R. Ding, A. Ellern, D.W. Armstrong, J. Am. Chem. Soc. 127 (2005) 593. J.L. Anderson, D.W. Armstrong, Anal. Chem. 77 (2005) 6453. A. Berthod, L. He, D.W. Armstrong, Chromatographia 53 (2001) 63. J. Ding, T. Welton, D.W. Armstrong, Anal. Chem. 76 (2004) 6819. F. Mutelet, J.N. Jaubert, J. Chromatogr. A 1102 (2006) 256. F. Mutelet, V. Butet, J.N. Jaubert, Ind. Eng. Chem. Res. 44 (2005) 4120. G. Inoue, Y. Iwai, M. Yasutake, K. Honda, Y. Arai, Fluid Phase Equilib. 251 (2007) 17.

17

[31] A. Berthod, J.J. Kozak, J.L. Anderson, J. Ding, D.W. Armstrong, Theor. Chem. Acc. 117 (2007) 127. [32] J. Liu, N. Li, G. Jiang, J.A. J¨onson, M. Wen, J. Chromatogr. A 1066 (2005) 27. [33] V. Pino, Q.Q. Baltazar, J.L. Anderson, J. Chromatogr. A 1148 (2007) 92. [34] X. Han, D.W. Armstrong, Acc. Chem. Res. 40 (2007) 1079. [35] S.A. Shamsi, N.D. Danielson, J. Sep. Sci. 30 (2007) 1729. [36] P.H. Shetty, P.J. Youngberg, B.R. Kersten, C.F. Poole, J. Chromatogr. 411 (1987) 61. [37] M.M. Waichigo, T.L. Riechel, N.D. Danielson, Chromatographia 61 (2005) 17. [38] M.M. Waichigo, N.D. Danielson, J. Sep. Sci. 29 (2006) 599. [39] M.M. Waichigo, B.M. Hunter, T.L. Riechel, N.D. Danielson, J. Liq. Chromatogr. Rel. Technol. 30 (2007) 165. [40] M. Reta, P.W. Carr, J. Chromatogr. A 855 (1999) 121. [41] H.A. Claessens, Trends Anal. Chem. 20 (2001) 563. [42] M.J. Ruiz-Angel, J.R. Torres-Lapasi´o, S. Carda-Broch, M.C. Garc´ıaAlvarez-Coque, J. Chromatogr. Sci. 41 (2003) 350. [43] L. He, W. Zhang, L. Zhao, X. Liu, S. Jiang, J. Chromatogr. A 1007 (2003) 39. [44] W. Zhang, L. He, Y.L. Gu, X. Liu, S. Jiang, Anal. Lett. 36 (2003) 827. [45] X. Xiao, L. Zhao, L. Xia, S. Jiang, Anal. Chim. Acta 519 (2004) 207. [46] R. Kaliszan, M.P. Marszałł, M.J. Markuszewski, T. B˛aczek, J. Pernak, J. Chromatogr. A 1030 (2004) 263. [47] M.P. Marszałł, R. Kaliszan, Crit. Rev. Anal. Chem. 37 (2007) 127. [48] M.P. Marszałł, T. B˛aczek, R. Kaliszan, J. Sep. Sci. 29 (2006) 1138. [49] M.P. Marszałł, T. B˛aczek, R. Kaliszan, Anal. Chim. Acta 547 (2005) 172. [50] A. Berthod, M.J. Ruiz-Angel, S. Huguet, Anal. Chem. 77 (2005) 4071. [51] L. Pan, R. LoBrutto, Y.V. Kazakevish, R. Thomson, J. Chromatogr. A 1049 (2004) 63. [52] F. Gritti, G. Guiochon, Anal. Chem. 76 (2004) 4779. [53] F. Tang, L. Tao, X. Luo, L. Ding, M. Guo, L. Nie, S. Yao, J. Chromatogr. A 1125 (2006) 182. [54] M.J. Ruiz-Angel, S. Carda-Broch, A. Berthod, J. Chromatogr. A 1119 (2006) 202. [55] Y. Polyakova, Y.M. Koo, K.H. Row, Biotechnol. Bioprocess. Eng. 11 (2006) 1. [56] S.J. Liu, F. Zhou, X.H. Xiao, L. Zhao, X. Liu, S.X. Jiang, Chin. Chem. Lett. 15 (2004) 1060. [57] H. Qiu, S.X. Jiang, X. Liu, J. Chromatogr. A 1103 (2006) 265. [58] H. Qiu, S.X. Jiang, X. Liu, L. Zhao, J. Chromatogr. A 1116 (2006) 46. [59] Y. Sun, B. Cabovska, C.E. Evans, T.H. Ridgway, A.M. Stalcup, Anal. Bioanal. Chem. 382 (2005) 728. [60] Q. Wang, G.A. Baker, S.N. Baker, L.A. Col´on, Analyst 131 (2006) 1000. [61] A. Berthod, in: D. Barcel´o (Ed.), Comprehensive Analytical Chemistry, vol. 38, Elsevier, Amsterdam, 2002. [62] A. Berthod, S. Carda-Broch, J. Liq. Chromatogr. Rel. Technol. 26 (2003) 1493. [63] A. Berthod, S. Carda-Broch, Anal. Bioanal. Chem. 380 (2004) 168. [64] K.E. Gutowski, G.A. Broker, H.D. Willauer, J.G. Huddleston, R.P. Swatloski, J.D. Holbrey, R.D. Rogers, J. Am. Chem. Soc. 125 (2003) 6632. [65] M.J. Ruiz-Angel, V. Pino, S. Carda-Broch, A. Berthod, J. Chromatogr. A 1151 (2007) 65. [66] W. Qin, S.F.Y. Li, Electrophoresis 23 (2002) 4110. [67] W. Qin, S.F.Y. Li, Analyst 128 (2003) 37. [68] M. Borissova, M. Vaher, M. Koel, M. Kaljurand, J. Chromatogr. A 1160 (2007) 320. [69] W. Qin, H. Wei, S.F.Y. Li, J. Chromatogr. A 985 (2003) 447. [70] W. Qin, S.F.Y. Li, J. Chromatogr. A 1048 (2004) 253. [71] E.G. Yanes, S.R. Gratz, M.J. Baldwin, S.E. Robinson, A.M. Stalcup, Anal. Chem. 73 (2001) 3838. [72] B. Cabovska, G.P. Kreishman, D.F. Wassell, A.M. Stalcup, J. Chromatogr. A 1007 (2003) 179. [73] T.F. Jiang, Y.L. Gu, B. Liang, J.B. Li, Y.P. Shi, Q.Y. Ou, Anal. Chim. Acta 479 (2003) 249. [74] P.L. Laamanen, S. Busi, M. Lahtinen, R. Matilainen, J. Chromatogr. A 1095 (2005) 164. [75] S. Qi, S. Cui, X. Chen, Z. Hu, J. Chromatogr. A 1059 (2004) 191.

18

A. Berthod et al. / J. Chromatogr. A 1184 (2008) 6–18

[76] S. Qi, Y. Li, Y. Deng, Y. Chen, X. Chen, Z. Hu, J. Chromatogr. A 1109 (2006) 300. [77] K. Tian, Y. Wang, Y. Chen, X. Chen, Z. Hu, Talanta 72 (2007) 587. [78] M.E. Yue, Y.P. Shi, J. Sep. Sci. 29 (2006) 272. [79] M.P. Marszałł, M.J. Markuszewski, R. Kaliszan, J. Pharm. Biomed. Anal. 41 (2006) 329. [80] M. Vaher, M. Koel, M. Kaljurand, Chromatographia 53 (2001) 302. [81] M. Vaher, M. Koel, M. Kaljurand, Electrophoresis 23 (2002) 426. [82] M. Vaher, M. Koel, M. Kaljurand, J. Chromatogr. A 979 (2002) 27. [83] Y. Francois, A. Varenne, E. Juillerat, A.C. Servais, P. Chiap, P. Gareil, J. Chromatogr. A 1138 (2007) 268. [84] Y. Francois, A. Varenne, E. Juillerat, D. Villemin, P. Gareil, J. Chromatogr. A 1155 (2007) 134. [85] L.M. Yuan, Y. Han, Y. Zhou, X. Meng, Z.Y. Li, M. Zi, Y.X. Chang, Anal. Lett. 39 (2006) 1439. [86] S.M. Mwongela, A. Numan, N.L. Gill, R.A. Agbaria, I.M. Warner, Anal. Chem. 75 (2003) 6089. [87] S.A.A. Rizvi, S.A. Shamsi, Anal. Chem. 78 (2006) 7061. [88] K. Tian, S. Qi, Y. Chen, X. Chen, Z. Hu, J. Chromatogr. A 1078 (2005) 181. [89] H. Zhang, K. Tian, J. Tang, S. Qi, H. Chen, X. Chen, Z. Hu, J. Chromatogr. A 1129 (2006) 304.

[90] P. Stepnowski, A. M¨uller, P. Behrend, J. Ranke, J. Hoffmann, B. Jastorff, J. Chromatogr. A 993 (2003) 173. [91] M.J. Ruiz-Angel, A. Berthod, J. Chromatogr. A 1113 (2006) 101. [92] M.J. Ruiz-Angel, A. Berthod, Presented at the 31st International Symposium on High Performance Liquid Phase Separations and Related Techniques, Ghent, June 17–21, 2007, Poster P01-10. [93] B. Buszewski, S. Kowalska, P. Stepnowski, J. Sep. Sci. 29 (2006) 1116. [94] S. Kowalska, B. Buszewski, J. Sep. Sci. 29 (2006) 2625. [95] P. Stepnowski, J. Nichthauser, W. Mrozik, B. Buszewski, Anal. Bioanal. Chem. 385 (2006) 1483. [96] J.R. Stuff, J. Chromatogr. 547 (1991) 484. [97] P. Stepnowski, W. Mrozik, J. Sep. Sci. 28 (2005) 149. [98] G. Le Rouzo, C. Lamouroux, C. Bresson, A. Guichard, P. Moisy, G. Moutiers, J. Chromatogr. A 1164 (2007) 139. [99] W. Qin, H. Wei, S.F.Y. Li, Analyst 127 (2002) 490. [100] M.J. Markuszewski, P. Stepnowski, M.P. Marszall, Electrophoresis 25 (2004) 3450. [101] D. Berthier, A. Varenne, P. Gareil, M. Digne, C.P. Lienemann, L. Magna, H. Olivier-Bourbigou, Analyst 129 (2004) 1257. [102] C. Villagran, M. Deetlefs, W.R. Pitner, C. Hardacre, Anal. Chem. 76 (2004) 2118.