perspectives in analytical chemistry: current and future ... · pdf fileanalytical...

Full Terms & Conditions of access and use can be found athttp://www.tandfonline.com/action/journalInformation?journalCode=batc20

Download by: [The UC San Diego Library] Date: 30 April 2017, At: 00:52

Critical Reviews in Analytical Chemistry

ISSN: 1040-8347 (Print) 1547-6510 (Online) Journal homepage: http://www.tandfonline.com/loi/batc20

Combination of Cyclodextrin and Ionic Liquidin Analytical Chemistry: Current and FuturePerspectives

Y. H. Boon, M. Raoov, N. N. M. Zain, S. Mohamad & H. Osman

To cite this article: Y. H. Boon, M. Raoov, N. N. M. Zain, S. Mohamad & H. Osman (2017):Combination of Cyclodextrin and Ionic Liquid in Analytical Chemistry: Current and FuturePerspectives, Critical Reviews in Analytical Chemistry, DOI: 10.1080/10408347.2017.1320936

To link to this article: http://dx.doi.org/10.1080/10408347.2017.1320936

Accepted author version posted online: 28Apr 2017.

Submit your article to this journal

View related articles

http://www.tandfonline.com/action/journalInformation?journalCode=batc20

http://www.tandfonline.com/loi/batc20

http://www.tandfonline.com/action/showCitFormats?doi=10.1080/10408347.2017.1320936

http://dx.doi.org/10.1080/10408347.2017.1320936

http://www.tandfonline.com/action/authorSubmission?journalCode=batc20&show=instructions

http://www.tandfonline.com/action/authorSubmission?journalCode=batc20&show=instructions

http://www.tandfonline.com/doi/mlt/10.1080/10408347.2017.1320936

http://www.tandfonline.com/doi/mlt/10.1080/10408347.2017.1320936

ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT 1

Combination of Cyclodextrin and Ionic Liquid in Analytical Chemistry: Current and

Future Perspectives

Y. H. Boona,1

, M. Raoova,*

, N. N. M. Zaina, S. Mohamad

b,c,2, H. Osman

d,3

aIntergrative Medicine Cluster, Advanced Medical & Dental Institute, Universiti Sains Malaysia,

Pulau Pinang 13200, Malaysia

bDepartment of Chemistry, Faculty of Science,Universiti Malaya, Kuala Lumpur 50603,

Malaysia.

cUniversiti Malaya Centre for Ionic Liquids (UMCiL), Department of Chemistry, Faculty of

Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia

dSchool of Chemical Sciences, Universiti Sains Malaysia, 11800, Pulau Pinang, Malaysia

*Corresponding Author. E-mail: [email protected]

1Corresponding Author. E-mail: [email protected]; [email protected];

[email protected]

2Corresponding Author. E-mail: [email protected]

3Corresponding Author. E-mail: [email protected]

Abstract

The growth in driving force and popularity of cyclodextrin (CDs) and ionic liquids (ILs) as

promising materials in the field of analytical chemistry has resulted in an exponentially increase

of their exploitation and production in analytical chemistry field. Cyclodextrins belong to the

family of cyclic oligosaccharides composing of α-(1,4) linked glucopyranose subunits and

possess a cage-like supramolecular structure. This structure enables chemical reactions to

mailto:[email protected]

ACCEPTED MANUSCRIPT


proceed between interacting ions, radical or molecules in the absence of covalent bonds.

Conversely, ionic liquids are an ionic fluids comprising of only cation and anion often with

immeasurable vapour pressure making them as green or designer solvent. The cooperative effect

between cyclodextrin and ionic liquid due to their fascinating properties, have nowadays

contributed their footprints for a better development in analytical chemistry nowadays. This

comprehensive review serves to give an overview on some of the recent studies and provides an

analytical trend for the application of CDs with the combination of ILs that possess beneficial

and remarkable effects in analytical chemistry including their use in various sample preparation

techniques such as solid phase extraction (SPE), magnetic solid phase extraction (MSPE), cloud

point extraction (CPE), microextraction (ME), and separation techniques which includes gas

chromatography (GC), high-performance liquid chromatography (HPLC), capillary

electrophoresis (CE) as well as applications of electrochemical sensors as electrode modifiers

with references to recent applications. This review will highlight the nature of interactions and

synergic effects between CDs, ILs and analytes. It is hoped that this review will stimulate further

research in analytical chemistry.

Keywords

analytical chemistry, cyclodextrin(s), ionic liquid(s), separation science, sample preparation,

sensor

ACCEPTED MANUSCRIPT


1.0 Introduction

Supramolecular chemistry is a new knowledge branch in chemistry which has been

gaining great attention recently. It gives a comprehensive idea that no covalent bonds are formed

between interacting species as most interactions involve host-guest interactions. Cyclodextrins

(CDs), one of the most profound host molecules in supramolecular chemistry, ideally fit various

kinds of guest molecules with suitable polarity and dimensions into their cavities (Ramo et al.,

2001; Malefetse et al., 2009; Singh and Bharti, 2010; Mohamad et al., 2011; Raoov et al., 2013,

2014b; Sambasevam et al., 2013; Surikumaran et al., 2014; Ain et al., 2015). This includes ionic

or molecular species such as branched or straight chain aliphatic, ketones, and aldehydes, organic

acids, alcohols, fatty acids, ionic liquid, and polar compounds like amines, oxyacids, and

halogens (Charoensakdi et al., 2007). CDs are pretty malleable and ready for chemical

modifications and functionalization. These unique properties enhances their potential capability

for complexation (Li and Purdy, 1992) thus making them valuable in the analytical chemistry

field.

Cyclodextrins belong to the series of macro cyclic oligosaccharides which are composed

of α (6), β (7), and γ (8) β–CD connected by α-1,4 glucopyranose units, with OH- functional

group located outside the surface and a lipophilic centre cavity that enables them to trap

hydrophobic molecules without forming any chemical bonds. These fascinating features of

cyclodextrins have been extensively studied in separations due to their ability to form a complex.

Basically, the size and shape selectivity of cyclodextrin will influences the separation parameter

because of the impact -stability constant of different magnitudes on molecular discrimination

(Schneiderman and Stalcup, 2000). In addition, chemical modification of the CDs structure, as

ACCEPTED MANUSCRIPT


well as the selective binding of analytes within the CD cavity, has led to remarkable advances in

analytical applications of CDs.

Ionic liquids are referred as liquefied organic salts at room temperature (RTIL) and are

poorly coordinated. The first IL was synthesized in 1914 but its importance in the field was not

realised till the late 70s and 80s. Generally, ionic liquids are made up of organic cations and

inorganic anions. They are designed to have a delocalized charge and one component is organic

in order to prevent the formation of stable crystal lattice (Devi, 2015). Ionic liquids have been

labelled as green recyclable alternatives to the conventional organic solvents and are developed

to be environmentally friendly in line with the sustainable chemistry concept (Hernández-

Fernández et al., 2010; Hallett and Welton, 2011; Rahim et al., 2011; Zaijun et al., 2011; Devi,

2015). They were widely used in analytical chemistry fields because of their fascinating

properties such as non-flammability, non-volatility, high polarity, low viscosity, and great

electrochemical stability. In addition, one important feature of ILs is that their desired properties

can also be produced by altering their combinations of cationic and anionic constituents. Because

of this versatile nature, ILs are regarded as “designer solvents”. They have either been directly

used or engineered to improve sensitivity, selectivity, and detection limit in analytical

applications. Specifically, these features create distinction for ILs and favour them to be applied

as extraction solvents and catalysts, electrode modifiers (Cao et al., 2011; Yu et al., 2013;

Mohamad et al., 2015; Sinniah et al., 2015; Mohd Rasdi et al., 2016) and modified sorbents in

the sample pre-treatment and modified chiral stationary phases or additives in separation

chemistry (Huang et al., 2010; Zhou et al., 2010; Zhang et al., 2011; Galán-cano et al., 2013;

ACCEPTED MANUSCRIPT


Raoov et al., 2014a; Chen and Zhu, 2016; Chen et al., 2016; Tokalıoğlu et al., 2016; Yang et al.,

2016).

Presently, a combination of CDs with ILs as advanced novel materials has received much

interest and is even being recognised as a versatile tool in analytical applications due to their

ability to give beneficial results. When both CDs and ILs are used in an analytical application,

such as, in separation studies, the functional group of the ionic liquid is able to improve the

extraction performance of cyclodextrin besides retaining the hydrophobic cavity of cyclodextrin

molecule (Raoov et al., 2013). The behaviour of these materials are mainly separation

mechanism dependent, which cover multiple interactions (e.g. electrostatic, hydrophobic, and ).

There are two types of CDs-ILs complex formation processes which are known as the

functionalization and loading process respectively as illustrated in Figure 1.1. Recently, the

importance of analytical application based on CDs with a combination of ILs were given much

attention. Therefore, this review will cover more of the applications of CDs and ILs in analytical

chemistry including their use in various sample preparation techniques such as solid phase

extraction (SPE), magnetic solid phase extraction (MSPE), cloud point extraction (CPE),

microextraction (ME), and separation techniques which include gas chromatography (GC), high-

performance liquid chromatography (HPLC), capillary electrophoresis (CE) as well as

application in electrochemical sensors. The cooperating effects between CDs and ILs which

emphasize the natural interaction and relationship between CDs, ILs and analytes will be

discussed in detail.

ACCEPTED MANUSCRIPT


2.0 Cooperating Effects between Ionic Liquid(s) and Cyclodextrin(s) in Separation

Techniques

Separations represent a large area of analytical chemistry. Since both ILs and CDs have

such a significant individual effect, combining them is always the choice in the separation

process. To date, among various types of separation processes, the Capillary Electrophoresis

(CE), High-Performance Liquid Chromatography (HPLC), and Gas Chromatography (GC) were

found to extensively utilize the combination of CDs and ILs.

2.1 Capillary Electrophoresis (CE)

CE is a crucial electrophoretic technique in chiral separation science due to low reagent and

sample consumption, simplicity, and high efficiency (Vidal et al., 2012). Nowadays in CE,

individual CD or mixtures of different CDs have been widely applied as additives in the buffer

for mobile phase (Schneiderman and Stalcup, 2000; Juvancz et al., 2008). However, the most

significant use of individual cyclodextrin in capillary electrophoresis has been identified to

covalently bind on the capillary wall for chiral separations. Due to the ability to exhibit host-

guest interaction with various water-insoluble molecules in their hydrophobic cavities, CDs have

proven its effectiveness in enhancing the selectivity of CE for chiral separations. Similarly, ionic

liquids are also being applied in CE due to their versatile and unique properties (Vaher et al.,

2007; Tang et al., 2014). Generally, ILs are applied as background electrolytes (BEG) in both

aqueous and non-aqueous capillary electrophoresis to control the electroosmotic flow (EOF) and

charging of analytes. Besides, ILs are used as capillary wall modifiers (Qi et al., 2014), micelle-

forming compounds (Pino et al., 2012), and as a new class of stationary phase (Stalcup and

ACCEPTED MANUSCRIPT


Cabovska, 2005) for CE as well as combining with CDs to form CD-IL chiral selectors. These

applications which will be highlighted throughout this review. Parameters that are normally

being investigated in CE for enantioseparation include buffer concentration and pH, type and

concentration of chiral selector, capillary temperature, type of organic modifier, and applied

voltage (Podar et al., 2016).

α-cyclodextrins (α-CDs) have been used in CE as additives into the buffer to improve the

detection of metal ions and ammonium where ionic liquids serve as a background electrolyte

(BGE) and a covalent coating reagent on the capillary surface (Qin and Li, 2004). The influence

of α-cyclodextrin on the sensitivity of metal ion detection was investigated in the bare and IL-

coated capillaries. The results revealed that the peak height ratio growth with increasing

concentration of α-CD increased till 12 mM, but there was no effect after 15 mM in bare

capillaries. This indicated that the use of α-CD does not greatly affect the mobilities or migration

order of metal ions due to the weak complexation between α-CD to other 18-crown-6 or metal

ions in the buffer. However, during the use of IL coated capillary in the presence of α-CD

containing buffer, the resolution of analytes was being enhanced in which the shoulder-merging

peaks were separated from the baseline. Authors observed that the resulting baseline using IL

coated capillary was more stable as compared to that of the uncoated. This is a beneficial

outcome of the cooperation between CDs and ILs in which increased the separation efficiency

and is probably attributed to the repulsive force between the positively-charged capillary surface

and cations leading to a lower detection limit even at a longer analysis time.

ACCEPTED MANUSCRIPT


Furthermore, eight racemic drugs (bifonazole, brompheniramine, chlorpheniramine,

liarozole, pheniramine, promethazine, tropicamide and warfarin) successfully underwent

enantioseparation with β-cyclodextrin functionalized chiral ionic liquid forming 6-O-2-

hydroxyltrimethylammonium-β-cyclodextrin tetrafluoroborate ([HPTMA-β-CD] [BF4]) as a

chiral selector in the CE (Jia Yu, Lihua Zuo, Hongjiao Liu, Lijuan Zhang, 2013). The effect of

background electrolyte (BGE) pH and ([HPTMA-β-CD] [BF4]) concentration on the separation

performance was examined and data obtained showed a significant chiral separation ability of

([HPTMA-β-CD] [BF4]) on the analyte from the sample matrices.

Meanwhile, the examination of chiral ionic liquids as additives to CDs for enantiomeric

separations of 2-arylpropionic acids (an anti-inflammatory drug) by capillary electrophoresis was

reported by Francois et al. (2007). Initially, individual chiral ILs (ethylcholine, EtChol and

phenylcholine PhChol) of bis(trifluoromethylsulfonyl)imide did not exhibit direct

enantioselectivity towards the model analytes, however, when different chiral selectors (di or

trimethyl-β-cyclodextrin) with the presence of those ILs in the electrolytes, result indicated that

there was an improvement in the separation resolution and selectivity. This observation was

attributed to the synergistic effects that exist between the CDs and chiral IL cation, due to

interactions between the analyte, chiral IL, and β-CD derivative. The apparent inclusion constant

of ionic liquid, EtChol and PhChol cations and the type of cyclodextrins used reflects the

influence of the cyclodextrin on the inclusion complex formation with the analyte (as shown in

Figure 2.1) that led to the drugs separation.

ACCEPTED MANUSCRIPT


In addition, the separation of anthraquinones from a Chinese Herb Paedicalyx attopervensis

Pierre ex Pitard was carried out employing β-cyclodextrin with ionic liquid (1-butyl-3-

methylimidazolium tetrafluoroborate, 1B-3MI-TFB) as a modifier in the capillary zone

electrophoresis (CZE) (Qi et al., 2004). In this research, the dissolution in CZE was influenced

by the weaker interaction within the cation and its encountered ion of the ionic liquid, which led

to the proposal that that 1B-3MI-TFB and β-CD were responsible for the separation. This is

illustrated in Figure 2.2 whereby the anthraquinones molecules probably interact with the β-CD

or imidazolium ions in the presence of β-CD-IL, causing the analytes to be totally or partially fit

into the cavity of β-CD. Meanwhile, free imidazolium ions in bulk solution will have stronger

interactions with the analytes which were not embedded into the cavity of β-CD. This creates a

phenomenon where more analytes have more interaction either with CD or IL, there will

indirectly be less analytes associate with free imidazolium ions in that bulk solution. The study

revealed that the interaction between analyte, β-CD, and IL could be relatively controlled by

hydrogen bonding, hydrophobic or ion-dipole/ion-induced-dipole interactions. Consequently, the

associated differences or fittings enable the effective separation of anthraquinones mxture.

In 2009, chiral cationic ionic liquid type surfactants, N-undecenoxycarbonyl-L-leucinol

bromide (L-UCLB), and 2,3,6-tri-O-methyl-β-cyclodextrin (TM-β-CD) were combined in the

Micellar Electrokinetic Chromatography (MEKC) to enantioseparate five profens (PROFs)

simultaneously (Wang et al., 2009a). The authors observed that at a low concentration of L-

UCLB (1.5-2.0 mM) CE buffer containing TM-β-CD, a good enantioseparation of the profens

was obtained with resolution in the range of 2.0-2.4. This improvement is due to the cooperating

interaction between TM-β-CD and L-UCLB, which in turn reduces the interaction of the L-

ACCEPTED MANUSCRIPT


UCLB with the capillary wall. Thus, all the enantiomers of PROFs were baseline resolved giving

a wide chiral window. In another study, the same authors investigated the interactions between

L-UCLB, TM-β-CD and profens using Affinity Capillary Electrophoresis (ACE) (Wang et al.,

2009b). An effective enantioseparation of the model analyte, for example fenoprofen was

achieved as a result of a synergistic effects between the ionic liquid and TM-β-CD as a dual

chiral selector which contributed to the different bonding constant values of R- and S-

fenoprofen.

A similar study of the enantiomeric separation describing the synergistic effect of amino

acid ester based chiral ionic liquids (AAILs) as additives in CE was carried out by Zhang et al.

(2013). L-alanine and L-valinetert butyl ester bis (trifluoromethane) sulfonimide (L-AlaC4NTf2

and L-ValC4NTf2) were used for the first time in CE to investigate their potential synergistic

effects with a series of chiral selectors (β-cyclodextrin derivatives such as methyl-β-CD,

hydropropyl-β-CD and glucose-β-CD) for enantiomeric separation of six racemic drugs

(naproxen, pra-noprofen and warfarin, carprofen, ibuprofen and ketoprofen. One of the important

findings of this study was during the presence of chiral ILs in the running buffer, systems with

three different β-CDs as chiral selectors that could improve the separation resolutions and

effective selectivity factor (αeff) for naproxen and pranoprofen, while Me-β-CD/chiral ILs

systems could, to some extent, improve the separation of warfarin. Authors speculated that when

the amino acid-derived chiral ILs were used individually, there was no enantioseparations were

observed. This clearly proves that synergistic effects do exist during the cooperation of β-CD

derivative and chiral ILs attributing to the fact that both entities do play a role in the chiral

recognition process which is vital for chiral separations.

ACCEPTED MANUSCRIPT


It has been demonstrated that hydroxypropyl-β-cyclodextrin (HP-β-CD) and chiral ionic

liquid ([TBA][L-ASP]) as selectors have a positive effect on the separation of four Cinchona

alkaloids (cinchonine/cinchonidine and quinine/quinidine) (Zhang et al., 2014). The finding

showed that, as the concentration of HP-β-CD increased, migration time became longer and EOF

value was reduced thus leading to an increment of the analyte’s resolution. This finding supports

the idea that the interactions between the ILs and CDs as chiral additive selectors affects the

chiral separation behaviour in which the chiral recognition is dependent on the complex stability

constant between the three entities; CDs, ILs, and the analytes.

Functionalization of β-CD with 3-methylimidazolium chloride to form mono-(3-methyl-

imidazolium)-β-cyclodextrin chloride (MIMCDCl) has been used as the chiral selector for the

enantioseparations of 14 dansyl amino acids (Tang et al. 2007a). The study concluded that the

chiral separation was highly determined by pH since the strength of complex formation with the

electrostatic interactions between each chiral selector and enantiomer was greatly influenced by

the protonation of those amino acids. This can be explained as, during the high pH, the

imidazolium group of cationic cyclodextrin may interact with the carboxylate group on the

analytes. At a high pH, the dansyl amino acids change from neutral to negative ions. Thus, the

inclusion complex became more stable as a result of electrostatic interactions formed between

the positively charged cyclodextrin and negatively charged amino acids. In addition to this, when

the MIMCDCI concentration increased, the ionic strength is also increased. This phenomena

shifted the complexation equilibrium towards the formation of more CD-analyte complexes, thus

mobility became slower. In another study, the same authors compared the effect of alkyl

substituents of alkylimidazolium on the enantioresolution ability of 6-mono(3-

ACCEPTED MANUSCRIPT


alkylimidazolium)-β-cyclodextrins as the chiral selectors towards dansyl amino acids by

capillary electrophoresis (Tang et al., 2007b). The evaluation of buffer pH and selector

concentration effect on the enantioseparation showed that the chiral selectors with a shorter chain

alkyl group (R=CnH2n+1, n 4) exhibited more excellent chiral recognition ability at selector

concentrations of 3 mM and buffer pH 5.0. One of the possible factor is the chiral recognition

mechanism where the ion pairing and host–guest interactions occurred between the dansyl amino

acid and β-cyclodextrins functionalized with alkylimidazolium.

In addition to this, Ong et al. (2005) also functionalized β-cyclodextrin-tosylate and β-

cyclodextrin chloride with different alkylimidazole (methyl, butyl, decyl, and 1,2-dimethyl) to

form 6-mono(alkylimidazolium)-β-CD tosylates and 6-mono(alkylimidazolium)-β-CD chlorides

as the chiral selectors in the chiral capillary electrophoresis to separate dansyl (Dns)-amino acids.

The effects were more obvious when short alkyl chain of the imidazolium was employed to

resolve the selected Dns-amino acids. Nevertheless, when the number of alkyl group of the

imidazole increased to decyl, poor selectivity and resolution abilities were displayed due to steric

hindrance which destabilized the complex formed between analyte and β-CD. The short alkyl

chain has more powerful interactions between the alkylimidazolium groups and carboxylate

groups of the analyte forming stable inclusion complex under optimum conditions.

Recent works of Zhou and co-workers (2016) described the development of background

electrolyte modifiers in the running buffer in order to simultaneously separate and quantify

tetracyclines (TCs) in water samples by capillary electrophoresis using β-cyclodextrin

functionalized ionic liquid to form mono-6-deoxy-6-(3-methylimidazolium)-β-cyclodextrin

ACCEPTED MANUSCRIPT


tosylate. The prepared modifiers successfully separated the tetracyclines with high stability and

good reproducibility. Authors compared the separation ability with and without β-CD-IL and

found that during the presence of an optimum concentration of 20 mmol/L β-CD-IL, all the TCs

achieved a good separation efficiency and longer migration time around 20-30 min under

optimized conditions such as pH of 7.2 for the buffer, a concentration of 10 mmol/L

concentration and a separation voltage of 15kV (Figure 2.3). This was probably due to the

electrostatic interaction of the fused silica capillary wall and organic cation of the β-CD-IL

polymer. It was also revealed that good solubility of β-CD-IL shielded only a part of silanol

groups in the capillary wall for its steric hindrance in the structure of CD group, so the

suppressed EOF still migrated from the anode to cathode. In addition to this, hydrogen bonding,

hydrophobic interactions, electrostatic interactions and inclusion complex interactions between

β-CD-IL and TCs also played a vital role in improving the separation efficiency. The β-CD

inclusion complex offers benefits such as high selectivity and stability thus, improving the

resolution of the TCs, demonstrating once again the potential separation ability of the β-CD-IL

polymer-treated capillary for TCs.

To sum up, interaction between CDs and ILs provide benefits in the modification of

electrophoretic separation. Table 1 summarizes the overall use of CDs-ILs combination as an

organic modifier or functionalized CDs with ILs in capillary electrophoresis.

2.2 Gas Chromatography (GC)

One of the wide range applications of ionic liquid as early as in 1999 was the stationary

phases in gas chromatography (Armstrong et al., 1999) due to their viscosity and wetting ability,

ACCEPTED MANUSCRIPT


which enabled them to be easily coated on the fused silica capillaries. There are many reviews

about the applications of ionic liquid (Cocalia et al., 2006; Hallett and Welton, 2011; Jiang et al.,

2014). The similarity between the reviews were that ILs are able to solubilize complex

macrocyclic molecules such as cyclodextrins, CDs. Thus, ILs can be considered helpful in the

separation processes. However, the application of CDs and ILs combination in GC is rarely and

scarce.

The first study of chiral separation carried out by Berthod and co-workers (2001) reported

on the use of ionic liquid, 1-butyl-3-methylmidazolium chloride to solubilize dimethylated-β-

cyclodextrin (BDM) and permethylated-β-cyclodextrin (BPM) in order to synthesis stationary

phases for capillary columns in GC-FID. It was suggested that the commercial column showed a

better enantiomer separation than the CD-IL modified column because of the complexes formed

between the imidazolium ion pair and cyclodextrin cavity, which prevented chiral recognition.

The resolution and selectivity factors obtained using the commercial column were overall better

than the RTIL containing column. However, in term of peak efficiencies, the RTIL capillary

column showed a noticeable improvement than the commercial column. This may probably be

due to the diameter of the CD-IL modified column which is twice shorter compared to the

commercial columns.

Nine years later, Huang and his groups (2010) prepared the GC-FID chiral stationary

phases made up of cyclodextrins functionalized ionic liquid. In this study, the charged

cyclodextrin GC chiral selectosr such as permethyl-6-(tripropylphosphonium)-β-cyclodextrin

iodide (TPP-BPM-I) and (permethyl-6-(butylimidazolium)-β-cyclodextrin iodide (BIM-BPM-I)

ACCEPTED MANUSCRIPT


were applied and successfully used to separate 56 types of chiral compounds. The properties of

the cationic cyclodextrin chiral selectors played a key role in improving the chiral recognition

on the stationary phase of the column. Thus, enantioseparations of more than one-third of the

test samples were improved using the new IL-based stationary phase. The CD-IL modified

column was also proven to be able to separate some compounds that were unable to separate

well using the commercial column. On the other hand, the IL-based column also enhanced the

peak efficiencies and gave better peak shapes for racemic analytes with higher polarities. The

crucial finding of this study was that good column performance may not be achieved in bulkier

ionic liquid matrix due to the presence of diminished electrostatic interaction and steric

hindrance effect caused by the bulky alkyl group in the material.

On the other hand, epoxides (ethers) and hydroxy esters, lactones in racemic mixtures

were separated by cyclodextrin-based ionic liquids as enantioselective stationary phases in GC-

FID (Costa et al., 2013). Four different chiral stationary phases namely mono-6-deoxy-6-(1-

vinyl-1H-imidazol-3-ium)-α-cyclodextrin, mono-6-deoxy-6-(pyridin-1-ium)-α-cyclodextrin,

mono-6-deoxy-6-(1-vinyl-1H-imidazol-3-ium)-β-cyclodextrin and mono-6-deoxy-6-(pyridin-1-

ium)-β-cyclodextrin were first synthesized using the protection/deprotection strategy.

Permethylated mono-6-hydroxycyclodextrins was the parent cyclodextrin for the derivation.

Authors reported that both enantiomers of ( -methyl laurate were separated at 140 in this

CD-IL modified stationary phase, which is unable to be attained by commercial CD column.

This finding proved that the combination of cyclodextrin and ionic liquid played a profound role

in the molecular interactions and recognition between the analyte and CSP which lead to the

chiral separation.

ACCEPTED MANUSCRIPT


2.3 High-Performance Liquid Chromatography (HPLC)

Nowadays, many researchers have directed their efforts towards studying new CD-IL

modified material as a stationary phase, not only in CE and GC, but also in HPLC. In doing so,

the application of cyclodextrin derivative bonded phases that readily separate enantiomers in

liquid chromatography have been reported (Chen et al., 2008; Zhou et al., 2010). β-CDs

derivatives has been nominated to be the famous chiral selectors for HPLC enantioseparations of

a wide range of racemates that were unable to be separated by native CDs (Tang et al., 1996).

Since cooperating ILs functionalised β-CD as chiral stationary phases in HPLC has been

attracting great interests, there is an increment in their applications nowadays.

The synthesis and application of β-CD derivative functionalized with 1-

methylimidazolium chloride to form mono-6-(3-methylimidazolium)-6-

deoxyperphenylcarbamoyl-β-cyclodextrin chloride (MPCCD) as chiral stationary phases (CSPs)

for the high-performance liquid chromatography and supercritical fluid chromatography were

reported by Ong and co-workers (2008) for enantioseparation of 10 chiral analytes from

derivatives of aromatic alcohols. Different weight percentages (15, 20 and 35%, w/w) of chiral

selector was coated onto silica gel to obtain different loading contents of CSPs. The result

showed that MPCCD-C20 obtained the best enantioseparation in HPLC and SFC whereby the

resolution ability of the studied analytes ranged from 3.83 to 5.65. The optimum loading

concentration attributed the best resolution ability in which synergistic effect existed between the

β-CD, ionic liquid, and analyte leading to a successful enantioseparation.

ACCEPTED MANUSCRIPT


In conjunction with this, another advanced study was conducted by the same authors

where four cationic β-CDs derivatives functionalized ionic liquid (Wang et al., 2008), namely

mono-6-(3-octylimidazolium)-6-deoxyper(3,5-dimethylphenylcarbamoyl)-β-cyclodextrin

chloride (ODPCCD), mono-6-(3-methylimidazolium)-6-deoxyper(3,5-

dimethylphenylcarbamoyl)-β-cyclodextrin chloride (MDPCCD), mono-6-(3-

methylimidazolium)-6-deoxy-perphenylcarbamoyl-β-cyclodextrin chloride (MPCCD) and mono-

6-(3-octylimidazolium)-6-deoxyperphenylcarbamoyl-β-cyclodextrin chloride (OPCCD) were

synthesized and physically coated onto porous spherical silica gel to prepare CSPs in HPLC for

enantioseparation of 18 racemic alcohols as model analytes. The authors pointed out that

ODPCCD showed the best performance among other CSPs due to the phenylcarbamoyl groups

that attached on the cyclodextrin ring and its n-octyl group on the imidazolium moiety which

improved analyte–chiral substrate interactions over CSPs. Analytes that possess electron

withdrawing group (EWG) such as halogen groups at the p-position on their aryl ring achieved

high selectivity on the cationic part exhibited by the CSPs because of the halogen group that

carried bigger electronegativity and formed electrostatic interaction with the cationic chiral

selectors coated on the surface of silica phase.

Another different approach was conducted using 1,2-dimethylimidazole or 1-amino-

1,2,3-triazole as ILs functionalized β-cyclodextrins (β-CDs) to form CSPs in HPLC for

enantioseparation of sixteen chiral aromatic alcohols derivatives and two racemic drugs in

acetonitrile-based polar organic mobile phase (Zhou et al., 2010). The four ILs functionalized β-

CDs included mono-6-deoxy-6-(1-amino-1,2,3-triazolium)-β-cyclodextrin tosylate, mono 6-

deoxy-6-(1,2-dimethylimidazolium)-β-cyclodextrin tosylate, mono-6-deoxy-6-(1-amino-1,2,3-

ACCEPTED MANUSCRIPT


triazolium)-β-cyclodextrin nitrate and mono-6-deoxy-6-(1,2-dimethylimidazolium)-β-

cyclodextrin nitrate. Excellent enantioseparation for most of the model analytes were achieved in

the presence of both CDs’ cationic and anionic moieties coated on the stationary phase. For the

cationic moieties, the imidazole group carried a positive charge and formed an electrostatic

interaction with the analytes, while the cationic triazole had a tendency to form ion-pairing

interaction with acidic analytes. For anion moieties, nitrate column achieved better chiral

recognition of analytes as compared to the tosylate column because nitrate is a weaker base

which has many H-bonding sites and less hindrance for easy approaches of analytes.

Similar study was applied to enantioseparate the analytes including aromatic alcohols,

chiral 1-phenyl-2-nitroethanol derivatives and ferrocene derivatives (Li and Zhou, 2014) using

four novel β-cyclodextrin (β-CD) derivatives functionalized by ionic liquid as the chiral

stationary phases (CSPs) coated on silica gel, namely, mono-6-deoxy-6-(p-N,N,N-

trimethylaminobenzimide)-β-CD tosylate (CSP), and mono-6-deoxy-6-(p-N-

methylimidazolemethylbenzimide)-β-CD tosylate (CSP), mono-6-deoxy-6-(p-N-

methylimidazolemethylbenzimide)-β-CD nitrate (CSP) and mono-6-deoxy-6-(p-

N,N,Ntrimethylaminobenzimide)β-CD nitrate (CSP). The anions structures on these CSPs play a

crucial role for analyte separation. CSP with the larger volume of tosylate anion was able to

separate smaller volume of analyte due to hydrogen-bonding and – interactions, while larger

volumes of analyte were more favourable to be separated by a small volume of nitrate anions on

CSPs due to the weaker steric effects. The study successfully proved that not only interactions

between different ionic groups and cavities (linkage group of a substituent) on β-CD but also ion

pairing interactions, hydrogen bonding interaction and electrostatic force between analytes and

ACCEPTED MANUSCRIPT


the cationic moiety on ionic liquid functionalized β-CD greatly influenced the enantioseparation

of the racemic.

A better enantioseparation of four β-blockers (metoprolol, atenolol, propranolol and

pindolol) was achieved using β-Cyclodextrin functionalized ionic liquid as chiral stationary

phase compared with the native β-CD based CSP as reported by Rahim et al (2016b). This

indicates that the introduction of ILs and interactions formed during the complexation with the

hydrophobic cavity of CD such as hydrogen bonding, hydrophobic, - and electrostatic

interactions at β-CD-BIMOTs CSP play a vital role to enhance the enantioseparation and chiral

recognition of the β-blockers on the stationary phase of HPLC. A recent study by the same

authors on enantioseparation of Flavonoids using β‑cyclodextrin functionalized 1-

benzylimidazole forming chiral stationary phase, β-CD-BIMOTs-CSP for HPLC column was

reported as well (Rahim et al., 2016a). Findings revealed that β-CD-BIMOTs-CSP showed a

better performance than native β-CD-CSP as a result of a synergistic effect between β-CD and

IL. For example, flavanone without any substituent on its aromatic rings exhibited less steric

hindrance, thus easing the formation of inclusion complexes in the cavity of β-CD-BIMOTs-

CSP. Furthermore, the aromatic ring and carbonyl group of flavanone also formed hydrogen

bonding and to interaction which might be useful for the enantio-recognition.Table 2

summarizes the overall combination use of CDs-ILs as chiral stationary phases in HPLC.

ACCEPTED MANUSCRIPT


3.0 Cooperating Effects between Ionic Liquid(s) and Cyclodextrin(s) in Sample

Preparation Techniques

Sample preparation is an important laborious step in analytical chemistry, prior to the

environment samples, due to their complex matrices and extremely low concentration of target

analytes. Nowadays, the analysis of the complex sample is still a problem if there are no proper

sample preparation techniques even there is a good evolution of analytical instrumentations.

Hereby, we will highlight the interesting facts based on the cooperating effects between CDs and

ILs that have been applied in different sample preparation techniques such as cloud point

extraction, solid phase extraction, magnetic solid phase extraction and microextraction

techniques.

3.1 Cloud Point Extraction (CPE)

CPE is one of the water-based sample preparation techniques in analytical chemistry for

the preconcentration of hydrophobic and hydrophilic species from sample matrices with the use

of non-ionic surfactants. There have been many reports on the use of cloud point extraction for

various compounds from different matrices (Frizzarin et al., 2016; Ghasemi and Kaykhaii, 2016;

Heidarizadi and Tabaraki, 2016; Naeemullah et al., 2016; Wang et al., 2016). However, the use

of cyclodextrin and ionic liquid based materials is still at early stages and has started to spur

significant interest in their use as modifiers in CPE system.

The interaction between ionic liquid and cyclodextrins becomes more significant when

both of them are being applied in the extraction processes. This was first proven by Noorashikin

and co-workers (2013) where methy, ethyl, propyl and aryl-parabens were extracted from water

ACCEPTED MANUSCRIPT


samples using a modifier made up of β-cyclodextrin (β-CD) functionalized ionic liquid (1-

methylimidazole, MIM) with a non-ionic surfactant, silicone–ethyleneoxide copolymer

(DC193C) forming CPE-DC193C-βCD-IL in the CPE. Different parameters were compared

between CPE-DC193C-βCD-IL and CPE-DC193C methods and findings indicate that CPE-

DC193C-βCD-IL was more effective. In the CPE system, the least amount of water in the

surfactant-rich layer represent higher detection of the analyte in the analysis. The technique of

employing β-CD-IL showed the largest amount of water loss compared with CPE-DC193C alone

because β-CD-IL was able to complex with a surfactant, thus the spaces remaining for water

were compressed leading to a small volume of water left and at the same time with paraben

being extracted simultaneously, in the surfactant-rich phase during the formation of micelles in

CPE process.

High log Kd value was exhibited by CPE-DC193C-βCD-IL (3.2-4.9) as compared to

CPE-DC193C (1-3.8) due to the chemical structure of β-CD. As the primary hydroxyls of β-CD

are located at the narrow side and secondary hydroxyls at the wider side, it is able to form

complexation with paraben, making β-CD water soluble while creating a hydrophobic inner

cavity that is compatible with the characteristics of the paraben. Likewise, parabens fit into the

cavity and complex with the inner part β-CD. Similarly, there are another possible interactions

between the imidazolium rings of ILs and parabens via to interactions and electrostatic

interactions. Thus, the functionalization of ILs to β-CD as a modifier increased the extraction

ability of paraben into the surfactant-rich phase from the aqueous phase. Therefore, we can point

out that interaction between CDs, ILs and paraben played a crucial role in enhancing the

extraction performance in CPE.

ACCEPTED MANUSCRIPT


Two years later, a modifier made up of cyclodextrin functionalized ionic liquid in CPE

for removal of phenolic compounds using spectrophotometer was reported (Zain et al., 2016).

The idea that β-cyclodextrin combined with ILs (1-benzylimidazole, BIM) and DC193C as

modifier was successfully promoted in the removal of hydrophilic and hydrophobic organic

pollutants from the selected aqueous samples. The β-CD–IL modifier gave a good extraction

result for the hydrophilic compound such as 4-nitrophenol (4-NP) compared to the 2,4,6-

tricholophenol (2,4,6-TCP). This can be explained using the electron withdrawing group (EWG)

concepts in which 4-NP has stronger – interactions than 2,4,6-TCP due to the fact that the

chloro group has a weaker electron—withdrawing ability compared to nitro group in 4-NP.

However, the extraction performance of both analytes was satisfactory based on the data

obtained and this is probably attributed to the formation of inclusion complex, hydrogen

bonding, interaction and electrostatic attraction between β-CD–IL, 4-NP, 2,4,6-TCP and

the DC193C surfactants during the CPE process. The study also identified that interaction

between the β-CD-IL as a modifier and non-ionic surfactant during CPE simplified the micellar

extraction procedure yet enhanced the pollutant removal efficiency.

3.2 Solid Phase Extraction (SPE)

Solid phase extraction (SPE) may be applied in a variety disciplines to provide faster and

more efficient sample preparation (Bhuiyan and Brotherton, 2002). It is known to be faster, safer,

and more economical than many traditional sample preparation techniques since it reduces

sample handling and transferring while the elimination of emulsion contributes to more

reproducible results. However, the choice of sorbent in SPE plays an important role since it

ACCEPTED MANUSCRIPT


influences parameters such as affinity, selectivity, sensitivity and method capacity. The

exploitation of different materials as sorbents was widely developed to obtain more selective

materials with higher adsorption capacity. In addition to this, SPE sorbent also plays an

important role in analyte recoveries. Thus, the relationship between the physical-chemical

characteristic of the target analytes and sorbent properties need to be taken into account so as to

develop a robust and efficient SPE method.

Scientists have extensively modified the SPE sorbent materials, for example,

immobilization of the material surface such as silica coated with ILs or functionalization with

ionic liquid on SPE sorbent (Vidal et al., 2012). Common techniques for the functionalization of

SPE resin include bonding, loading, and sol–gelling technology. However, among those

modifications, only a few works reported the use of cyclodextrin and an ionic liquid as modified

SPE sorbents.

The first works involving the cyclodextrin-ionic liquid as polymer sorbent was published

by Malefetse et al. (2009). Cyclodextrin functionalized ionic liquid followed by polymerization

employed as the SPE sorbent with the prevalence CDs showed an enhanced absorption capability

in removing organic pollutants p-nitrophenol (PNP), 2,4,6-trichlorophenol (TCP) from water,

whereas ILs were reported to absorb heavy metals (Cr6+

) in aqueous media. This CD-IL polymer

was found to have a higher affinity towards the extraction of PNP than TCP but overall it

performed better than native the CD. This can be explained by the compatible analyte structure

that fits into the CD cavity. Whereas, functionalized IL on CD acts as a chelating group to form

complexes with metal. It is important to point out that the combination of the imidazolium ring

ACCEPTED MANUSCRIPT


from the ionic liquid onto the CD backbone contributes to the improvement of the polymer

moiety for absorption.

Ionic liquid ([C4min] PF6) loaded β-Cyclodextrin cross-linked polymer (β-CDCP) as an

SPE material has been proven to be adequate in the separation of Chrysophanol (Chry) in drug

samples (Ping et al., 2013). The retention efficiency of Chry on IL-β-CDCP was greater than β-

CDCP without loaded ionic liquid (native polymer) because the absorption ability of β-CDCP

was improved in the presence of hydrophobic ionic liquid. Besides, study revealed that the

inclusion ability of Chry towards IL-β-CD was stronger (113.64 Lmol-1)

than that of β-CD (38.54

Lmol-1

). This is most probably due to the favourable interaction between IL and β-CD that

contributed to the higher complexation ability between Chry and cyclodextrin.

Apart from that, Magnolol was also separated from drug samples by ionic liquids

functionalized β-cyclodextrin cross-linked polymer (mono-6-deoxy-6-(1,2-dimethylimida-

zolium)-β-cyclodextrin (ILs-β-CDCP) as solid phase extraction sorbent by Zhou and Zhu (2014).

Magnolol is electrically negative in strong alkaline (the dissociation constants of magnolol pKa1

and pKa2 are about 7.10 and 10.58). Therefore, ILs-β-CDCP showed a higher adsorption

efficiency of magnolol compared to that of β-CDCP due to the electrically negative of magnolol

which formed electrostatic attraction with the cation of the ionic liquid.

The same authors also explored the use of ionic liquid- functionalized β-cyclodextrin

cross-linked polymer, namely mono-6-deoxy-6-imidazole-β-cyclodextrin polymer (β-CDIMCP),

as a new solid phase adsorbent to separate trace amounts of kaempferol (flavonol antioxidant) in

food sample (Zhou et al., 2014). Due to the hydrogen-bonding interaction existed between the

ACCEPTED MANUSCRIPT


lone pair electron on the nitrogen atom of imidazole ring and the proton of the hydroxyl group in

kaempferol, adsorption efficiency of kaempferol on β-CDIMCP was higher than that of β-

CDCP. The IL-β-CD materials were successfully tested in the separation of kaempferol from the

food samples.

Another food analysis on the separation of Linuron (urea herbicides) using ionic-liquid-

loaded β-Cyclodextrin followed by polymerization as SPE material was reported by Feng et al.

(2015). The study was based on the introduction of an ionic liquid ([C6min] [PF6]) loaded β-

cyclodextrin cross-linked polymer (IL-β-CDCP) as the resin and found that linuron adsorption

on IL-β-CDCP was markedly enhanced by the hydrophobicity of resin polymer due to the

hydrophobic ionic liquid. The adsorption capacity of IL-β-CDCP was investigated as well and it

was reported that the adsorption ability of IL-β-CDCP towards linuron increased because of the

smaller polymer particle size which led to a greater specific surface area in adsorbing more

analytes. Authors described that the cross-linked polymer increased the area of contact between

water and ionic liquid which sped up the extraction and separation process in food samples. This

implies that an interaction between CD-IL under polymerization will result in a larger surface

area of adsorbent, which is relevant for the depollution techniques nowadays.

Imidazole and β-cylcodextrin seem to be the most common ionic liquid and cyclodextrin

groups used for the polymerization of SPE resin. Raoov et al. (2014a) reported on the

combination of benzylimidazole and β-cylcodextrin followed by polymerization forming a new

polymer (βCD-BIMOTs-TDI) as an adsorbent in SPE to extract phenols from water samples.

The pH study was used to evaluate the stability of the CD-IL materials and results showed that

ACCEPTED MANUSCRIPT


the sorbents were the most stable at pH 6 and can be justified by the adsorption mechanisms

from hydrogen bonding, Van Der Waals forces, and inclusion complexes. However, authors

proposed that the inclusion complex formation was the main interaction since the β-CD cavity

was unaffected during the polymerization process rather than other interactions. At low pH,

phenol will undergo protonation while in high pH the phenol will be deprotonated and these two

forms of phenol are unable to complex with CD. A comparison with the native β-Cylodextrin

polymer (βCD-TDI) and commercial SPE sorbents such as C18 silica, HR-X, and HR-P

adsorbents proved that βCD-BIMOTs-TDI sorbent produced the highest recoveries of phenols as

compared to others. The IL-β-CD materials were successfully evaluated in the extraction of

phenols in water samples.

In 2016, the number of papers that were published on the use of ILs and cyclodextrins

increased slightly. Chen et al. (2016) studied the applicability of using the Fe3O4@ionic liquids-

β-cyclodextrin polymer as magnetic solid phase extraction (MSPE) sorbent (Fe3O4@ILs-β-

CDCP) for speciation analysis of Mn(II)/Mn(VII) in water samples. Since the surface charge of

the adsorbent depends on pH and the metal ions may exist in a different form based on pH, pH

become one of the key parameters in the study. The pH effect conducted in a ranged from 3 to 11

and both Mn(II) and Mn(VII) showed strong interaction simultaneously at pH 10.0 due to the

result of comprehensive function which mainly includes electrostatic attraction, chemical

reaction (inclusion complex) and intermolecular forces between the magnetic nanoparticles, β-

CD, IL, and metal ions. It must be highlighted that ILs which are able to act as a chelating agent

to complex with metal also increased the selectivity of polymer towards the metal ions. The

ACCEPTED MANUSCRIPT


schematic illustration of magnetic solid phase extraction (MSPE) process using Fe3O4@ILs-β-

CDCP as adsorbent is shown in Figure 2.4.

Furthermore, Qin and coworkers immobilized a α-picoline-based ionic liquid onto β-CD

in order to obtain the α-picoline-based ionic liquid-β-cyclodextrin cross-linked polymer (ILs-β-

CDCP) in SPE to separate lornoxicam (non-steroidal anti-inflammatory drug) from blood

samples (Qin and Zhu, 2016b). The pH study showed that the adsorption efficiency of

lornoxicam into the cavity of ILs-β-CDCP was the highest at pH 7.0 and this retention could be

due to the hydrophobic forces of the CD’s cavity and strong interaction between

lornoxicam molecules and pyridine ring of IL. The adsorption behavior of lornoxicam on ILs–β-

CDCP was investigated through adsorption kinetics, thermodynamics model, and inclusion

complexation and ILs-β-CDCP was found to fitted into the pseudo second order model showing

lornoxicam adsorbed onto ILs–β-CDCP by chemisorption mechanism.

Ping et al., 2014; Qin and Zhu, 2016a very recently published two papers regarding the

extraction of Allura Red-food colouring and rhodamine B-textile colorant from food samples

using β-cyclodextrin functionalized ionic liquid cross-linked polymer for Allura Red and β-

cyclodextrin loaded ionic liquid cross linked polymer for rhodamine B. Authors observed that

adsorption of both colorants on the ionic liquid-β-cyclodextrin-cross-linked polymer was better

than the native material at pH 3 due to the hydrophobicity of the polymer after the introduction

of ionic liquid. The retention efficiency of both analytes on the cross-linked polymer was about

80-90% with the pH ranging from 2.0-6.0 and then decreased at higher pH values. Since the

dissociation constant (pKa) of both analytes is around 3, the major form of both analytes exists in

a molecular form which is much stronger than its ionic form, thus, promoting Allura Red and

ACCEPTED MANUSCRIPT


rhodamine B to be embedded into the ionic liquid cross-linked polymer. A comparison with

other previous reported methods also showed that ionic liquid modified β-cyclodextrin cross-

linked polymer gave a higher sensitivity, linear dynamic range and was an easy operation. Table

3 summarizes the overall combination use of CDs-ILs as SPE cross-linked polymer sorbents.

3.3 Microextraction (ME)

3.3.1 Dispersive Solid Phase Microextraction (DSPME)

The first study about ionic liquid modified cyclodextrin for dispersive solid phase

microextraction sorbent was published by Yang et al. (2016). Four different types of hydrophilic

ILs such as 1-octyl-3-methylimidazolium hexafluorophosphate [OMIM]PF6, 1-octyl-3-

methylimidazolium-bis(trifluoromethylsulfonyl)imide [OMIM]NTF2, 1-hexyl-3-

methylimidazolium hexafluorophosphate [HMIM]PF6, and 1-hexyl-3-methylimidazolium-

bis(trifluoromethylsulfonyl)imide [HMIM]NTF2 were coated on the β-CD/ATP to test their

ability as potential modifiers for the sorbent. The developed material was proven to exhibit

higher extraction recoveries when using ILs composed of [OMIM]+ than those containing

[HMIM]+

, which supported the fact that the extraction ability increases when the ILs’ alkyl

chain increases. Besides, the ILs also became more hydrophobic from PF6-

to NTF2-

which

showed beneficial influences towards the extraction process. Overall, IL-β-CD/ATP showed

higher recoveries when compared to native sorbents such as blank ATP and other ATP-based

sorbents. Authors explained this phenomena through the physical absorption and larger surface

area of ATP coated on IL-β-CD, strong anion-exchange ability between IL and analytes.

ACCEPTED MANUSCRIPT


Furthermore, the introduction of β-CD also improved the detection sensitivity corresponding to

the hydrophobic interactions and -cation between target analytes and absorbents.

4.0 Electrochemical Sensors

Electrochemistry is also another channel for the wide range used of CDs-ILs nowadays. It

started to gain research interest due to its ability to detect analyte at a lower electrochemical

potential, high detection current, sensitivity, and selectivity. Basically, the combination of CDs

and ILs is applied as an electrode modifier due to its beneficial and remarkable effects for the

study.

Modification of biocompatible hybrid film of β-cyclodextrin (β-CD) onto glass carbon

electrode (GCE) using ILs, 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4) for

electrochemical biosensor was reported (Cao et al., 2011). Charged transfer resistance (Rct) value

of the [Fe(CN)6]3-

/4-

probe showed 239.1 at bare GCE but increased to 943.2 after the

introduction of β-CD onto the surface of GCE. However, introduction of ILs onto the β-CD film,

the Rct values of β-CD/ILs film decreased to 306.7 which attributed to the excellent electronic

conductivity of ILs that eased the transfer of an electron between the [Fe(CN)6]3-

/4-

electrode and

probe. Electron transfer between the electrode surface and Horseradish peroxidase (HRP) was

investigated and data indicated that the amphiphilicity of β-CD and ability of β-CD to form

supermolecular complex could stabilize the composite matrix with ILs and HRP. The synergic

effect resulting from β-CD and ILs have raised not only the high selectivity and sensitivity of the

biosensor, but also quick response and low detection limit towards targeted analyte.

ACCEPTED MANUSCRIPT


Meanwhile, the preliminary electrochemical study of modified magnetite nanoparticles

Fe3O4 coated with β-cyclodextrin-functionalized ionic liquid, 1-methylimidazole forming (Fe3O4-

β-CD-IL) was examined (Sinniah et al., 2015). The cyclic voltammograms of bare GCE, Fe3O4,

Fe3O4-β-CD, and Fe3O4 -β-CD-IL were recorded in the aqueous solution of 5 mM Fe(CN)63-/4-

solution containing 0.1 M phosphate buffer solution (PBS) (1:1) at a scan rate of 100mVs -1

. The

peak-to-peak separation ( Ep) at bare GCE was about 148, but after the electrode was coated

with MNPs, the separation turned to about 81 mV for Fe3O4/GCE, 75 mV for Fe3O4-β-CD/GCE

and 69 mV for Fe3O4-β-CD-IL/GCE. Fe3O4-β-CD-IL/GCE showed a relatively rapid electron

transfer compared to bare GCE which was probably attributed to the fascinating electrical

conductivity of CD-IL and also MNPs with large surface area properties could speed up the

electron transfer rate between the electrode surface and Fe(CN)63-/4-

. The electrodes were then

used to detect bisphenol A (BPA) and the result revealed that β-CD-IL played a significant role

in improving peak current and BPA recognition.

Mohamad et al. (2015) and Mohd Rasdi et al. (2016) studied the molecular interaction of

2,4-dichlorophenol (2,4-DCP) in sensor application using β-cyclodextrin functionalized ionic

liquid, mono-6-deoxy-6-(3-benzylimidazolium)-β-cyclodextrin tosylate (β-CD-BIMOTs)

through cyclic voltammetry. In this work, the determination of 2,4-DCP was carried out using

modified electrodes by mixing β-CD-BIMOTs with carbon paste electrode (CPE). Compared to

the native β-CD/CPE (1.24 µA) and bare CPE (0.78 µA), the electrochemical behavior of 2,4-

DCP at β-CD-BIMOTs/CPE showed the highest oxidation peak current (1.28 µA) revealing the

good electrical properties of ILs on CPE modified β-CD-BIMOTs which improved the rate of

electron transfer among the inclusion complex (formed between β-CD-BIMOTs -2,4-DCP) and

ACCEPTED MANUSCRIPT


the electrode surface with 2,4-DCP. Overall, combination of β-CD and IL with CPE showed a

greater improvement in determining the 2,4-DCP for this study.

Furthermore, the proposed β-CD-BIMOTs/CPE showed a higher selectivity and

sensitivity, wide linear range and simple electrode fabrication process as compared with the other

electrochemical methods (Mohd Rasdi et al., 2016). As per the authors, improvement of the peak

current probably corresponds with the strong binding affinity of 2,4-DCP towards β-CDBIMOTs

via inclusion complexes, electrostatic and – interactions. On the other hand, a stable host-

guest inclusion complex with the guest analyte was also achieved due to the hydrophobic inner

cavity of cyclodextrin besides the – interactions between imidazolium ring and 2,4-DCP. The

positive charge of the imidazolium ring provided a “pathway” for 2,4-DCP to attach the

electrode surface, and yet enhanced the rate of electron transfer of 2,4-DCP. On top of that, the

author also revealed that the electroactivity of graphite particles which have contact with IL give

rise to the larger capacitive current of β-CD-BIMOTs/CPE as compared to bare CPE and β-

CD/CPE (Opallo and Lesniewski, 2011).

Apart from that, detection of bisphenol A (BPA) by the voltammetric sensor was also

carried out by Yu et al. (2013) using β-cyclodextrin and ionic liquid-based carbon paste electrode

(β-CD/ILCPE). The super conductive binder made up of ionic liquid 1-butyl-3-

methylimidazolium tetrafluoroborate (BMIMBF4) in the composition of carbon paste greatly

improved the conductivity, compatibility, and polarity of the sensor. The decrease in the

difference between peak potentials ( p) is a good implication of the use of ILs. The

conductivity, electroactive area, and pre-concentration effect of the composite electrode,

increased when the ionic liquid was added into the mineral oil. The kinetic process of the sensor

ACCEPTED MANUSCRIPT


was investigated on (β-CD/ILCPE) and it was found that the electron-transfer process took

placed at carbon/IL interface was speeded up. The electron transfer resistance (Ret) decreased

remarkably after the use of IL. This could be attributed to the good ionic conductivity property

of ILs that accelerated the transportation of electrons between the probe and electrode. A poor

cyclic voltammograms response towards BPA was obtained in the absence of ILs and β-CD.

However, it showed an increment and improvement after the replacement of ionic liquid as a

binder. This can be explained by the inherent properties of ILs which are able to resolve the

substrate and other modifiers existing in the paste. BPA can be extracted and assembled on the

sensor more readily due to the hydrogen bonding, electrostatic, and interaction. In addition

to this, the current oxidation current of BPA at β-CD/ILCPE showed a better-shaped oxidation

peak as compared to IL/CPE. This could be due to the hydrophobic cavity of β-CD as an

attachment site for BPA to carbon for heterogeneous electron transfer in the presence of IL and a

better solubility of polar analytes in IL binder. To sum up, β-CD non-covalently functionalized

ILCPE has been successfully tested on the detection of BPA. Table 4 summarizes the overall

uses of CDs-ILs as electrode modifier in electrochemical sensors.

4.0 Conclusion and Future Perspective

As discussed in previous sections, recent years have seen the emergence of a significant

number of papers concerning the use of CDs-ILs combination in various types of analytical

applications. Despite this, the literature concerning their combination effects is still relatively

scarce. Thus, we have reviewed the recent works on CDs-ILs as modified materials for the

efficient and successful removal, extraction and separation of the studied analytes in selected

sample matrices. In general, the merits of CDs and ILs united together are prior to the multiple

ACCEPTED MANUSCRIPT


interactions (hydrogen bonding, electrostatic, to et al.) making them possess high potential

ability in different analytical techniques including sample preparation techniques such as solid

phase extraction (SPE), magnetic solid phase extraction (MSPE), cloud point extraction (CPE),

microextraction (ME), and separation techniques like gas chromatography (GC), high-

performance liquid chromatography (HPLC), capillary electrophoresis (CE) as well as

application in electrochemical sensor as electrode modifier owing to their important interaction

between CDs, ILs, and analytes, respectively.

On the whole, a wider combination and cooperating effect of CDs and ILs can be further

examined, which will probably lead scientists to explore more and new knowledge in material

sciences. All these efforts are expected to help flourish the full potential of CDs-ILs and make

them even more important and valuable within analytical chemistry fields in the future.

The authors declare no conflict of interest.

5.0 Acknowledgement

The authors would like to seize this opportunity to express their gratitude to Universiti

Sains Malaysia for the USM Research University Grant (1001/CIPPT/811322), and Fundamental

Research Grant Scheme, Ministry of Higher Education (MOHE), Malaysia (FRGS,

203/CIPPT/6711557) for their financial support.

ACCEPTED MANUSCRIPT


6.0 References

Ain, S.; Kumar, B.; Pathak, K. Cyclodextrins: Versatile Carrier in Drug Formulations and

Delivery Systems. Int. J. Pharm. Chem. Biol. Sci. 2015, 5 (3), 583–598.

Armstrong, D. W.; He, L.; Liu, Y. S. Examination of Ionic Liquids and Their Interaction with

Molecules, When Used as Stationary Phases in Gas Chromatography. Anal. Chem. 1999,

71 (17), 3873–3876.

Berthod, A.; He, L.; Armstrong, D. W. Ionic Liquids as Stationary Phase Solvents for

Methylated Cyclodextrins in Gas Chromatography. Chromatographia 2001, 53 (1/2), 63–

68.

Bhuiyan, A. a; Brotherton, H. O. Solid Phase Extraction of Pesticides with Determination by Gas

Chromatography. 2002, 56, 18–26.

Cao, A.; Ai, H.; Ding, Y.; Dai, C.; Fei, J. Biocompatible Hybrid Film of β-Cyclodextrin and

Ionic Liquids: A Novel Platform for Electrochemical Biosensing. Sensors Actuators, B

Chem. 2011, 155, 632–638.

Charoensakdi, R.; Murakami, S.; Aoki, K.; Rimphanitchayakit, V.; Limpaseni, T. Cloning and

Expression of Cyclodextrin Glycosyltransferase Gene from Paenibacillus Sp. T16 Isolated

from Hot Spring Soil in Northern Thailand. J. Biochem. Mol. Biol. 2007, 40 (3), 333–340.

Chen, J.; Zhu, X. Magnetic Solid Phase Extraction Using Ionic Liquid-Coated Core-Shell

Magnetic Nanoparticles Followed by High-Performance Liquid Chromatography for

Determination of Rhodamine B in Food Samples. Food Chem. 2016, 200, 10–15.

ACCEPTED MANUSCRIPT


Chen, S.; Qin, X.; Gu, W.; Zhu, X. Speciation Analysis of Mn(II)/Mn(VII) Using Fe3O4@ionic

Liquids-β-Cyclodextrin Polymer Magnetic Solid Phase Extraction Coupled with ICP-OES.

Talanta 2016, 161, 325–332.

Chen, X.; Zhou, Z.; Yuan, H.; Meng, Z. Preparation and Chiral Recognition of a mono[6A-N-1-

(2-Hydroxy)- Phenylethylimino-6A-Deoxy]-β-Cyclodextrin HPLC Stationary Phase. J.

Chromatogr. Sci. 2008, 46 (9), 777–782.

Cocalia, V. A.; Holbrey, J. D.; Gutowski, K. E.; Bridges, N. J.; Rogers, R. D. Separations of

Metal Ions Using Ionic Liquids : The Challenges of Multiple Mechanisms *. 2006, 11 (2),

0–5.

Costa, N.; Matos, S.; Da Silva, M. D. R. G.; Pereira, M. M. a. Cyclodextrin-Based Ionic Liquids

as Enantioselective Stationary Phases in Gas Chromatography. Chempluschem 2013, 78,

1466–1474.

Devi, R. Ionic Liquids-Useful Reaction Green Solvents for the Future ( A Review ). 2015, 2 (2),

26–29.

Feng, G.; Ping, W.; Qin, X. X.; Liu, J.; Zhu, X. Ionic-Liquid-Loaded β-Cyclodextrin-Cross-

Linked Polymer Solid-Phase Extraction for the Separation/Analysis of Linuron in Fruit and

Vegetable Samples. Food Anal. Methods 2015, 8 (9), 2315–2320.

François, Y.; Varenne, A.; Juillerat, E.; Villemin, D.; Gareil, P. Evaluation of Chiral Ionic

Liquids as Additives to Cyclodextrins for Enantiomeric Separations by Capillary

Electrophoresis. J. Chromatogr. A 2007, 1155 (2), 134–141.

ACCEPTED MANUSCRIPT


Frizzarin, R. M.; Portugal, L. a.; Estela, J. M.; Rocha, F. R. P.; Cerdà, V. On-Line Lab-in-

Syringe Cloud Point Extraction for the Spectrophotometric Determination of Antimony.

Talanta 2016, 148, 694–699.

Galán-cano, F.; Alcudia-león, M. C.; Lucena, R.; Cárdenas, S.; Valcárcel, M. Ionic Liquid

Coated Magnetic Nanoparticles for the Gas Chromatography / Mass Spectrometric

Determination of Polycyclic Aromatic Hydrocarbons in Waters. J. Chromatogr. A 2013,

1300, 134–140.

Ghasemi, E.; Kaykhaii, M. Application of Micro-Cloud Point Extraction for Spectrophotometric

Determination of Malachite Green, Crystal Violet and Rhodamine B in Aqueous Samples.

Spectrochim. Acta - Part A Mol. Biomol. Spectrosc. 2016, 164, 93–97.

Hallett, J. P.; Welton, T. Room-Temperature Ionic Liquids: Solvents for Synthesis and Catalysis.

2. Chem. Rev. 2011, 111 (5), 3508–3576.

Heidarizadi, E.; Tabaraki, R. Simultaneous Spectrophotometric Determination of Synthetic Dyes

in Food Samples after Cloud Point Extraction Using Multiple Response Optimizations.

Talanta 2016, 148, 237–246.

Hernández-Fernández, F. J.; De Los Ríos, A. P.; Ginestá, A.; Sánchez-Segado, S.; Lozano, L. J.;

Moreno, J. I.; Godínez, C. Use of Ionic Liquids as Green Solvents for Extraction of Zn2+,

Cd2+, Fe3+ and Cu2+ from Aqueous Solutions. Chem. Eng. Trans. 2010, 21, 631–636.

Huang, K.; Zhang, X.; Armstrong, D. W. Ionic Cyclodextrins in Ionic Liquid Matrices as Chiral

Stationary Phases for Gas Chromatography. J. Chromatogr. A 2010, 1217, 5261–5273.

ACCEPTED MANUSCRIPT


Jia Yu, Lihua Zuo, Hongjiao Liu, Lijuan Zhang, X. G. Synthesis and Application of a Chiral

Ionic Liquid Functionalized β-Cyclodextrin as a Chiral Selector in Capillary

Electrophoresis. Biomed. Chromatogr. 2013, 1–28.

Jiang, C.; Sun, Y.; Yu, X.; Gao, Y.; Zhang, L.; Wang, Y.; Zhang, H.; Song, D. Application of

C18-Functional Magnetic Nanoparticles for Extraction of Aromatic Amines from Human

Urine. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2014, 947–948, 49–56.

Juvancz, Z.; Kendrovics, R. B.; Iványi, R.; Szente, L. The Role of Cyclodextrins in Chiral

Capillary Electrophoresis. Electrophoresis 2008, 29 (8), 1701–1712.

Li, S.; Purdy, W. C. Cyclodextrins and Their Applications in Analytical Chemistry. Chem. Rev.

1992, 92 (6), 1457–1470.

Li, X.; Zhou, Z. Enantioseparation Performance of Novel Benzimido-β-Cyclodextrins

Derivatized by Ionic Liquids as Chiral Stationary Phases. Anal. Chim. Acta 2014, 819,

122–129.

Malefetse, T. J.; Mamba, B. B.; Krause, R. W.; Mahlambi, M. M. Cyclodextrin-Ionic Liquid

Polyurethanes for Application in Drinking Water Treatment. Water SA 2009, 35 (5), 729–

734.

Mohamad, S.; Surikumaran, H.; Raoov, M.; Marimuthu, T.; Chandrasekaram, K.; Subramaniam,

P. Conventional Study on Novel Dicationic Ionic Liquid Inclusion with β-Cyclodextrin.

Int. J. Mol. Sci. 2011, 12, 6329–6345.

Mohamad, S.; Chandrasekaram, K.; Rasdi, F. L. M.; Manan, N. S. A.; Raoov, M.; Sidek, N.;

ACCEPTED MANUSCRIPT


Fathullah, S. F. Supramolecular Interaction of 2,4-Dichlorophenol and β-Cyclodextrin

Functionalized Ionic Liquid and Its Preliminary Study in Sensor Application. J. Mol. Liq.

2015, 212, 850–856.

Mohd Rasdi, F. L.; Mohamad, S.; Abdul Manan, N. S.; Nodeh, H. R. Electrochemical

Determination of 2,4-Dichlorophenol at β-Cyclodextrin Functionalized Ionic Liquid

Modified Chemical Sensor: Voltammetric and Amperometric Studies. RSC Adv. 2016, 6,

100186–100194.

Naeemullah; Kazi, T. G.; Tuzen, M. Development of Novel Simultaneous Single Step and

Multistep Cloud Point Extraction Method for Silver, Cadmium and Nickel in Water

Samples. J. Ind. Eng. Chem. 2016, 35, 93–98.

Noorashikin, M. S.; Raoov, M.; Mohamad, S.; Abas, M. R. Cloud Point Extraction of Parabens

Using Non-Ionic Surfactant with Cylodextrin Functionalized Ionic Liquid as a Modifier.

Int. J. Mol. Sci. 2013, 14, 24531–24548.

Ong, T.; Wang, R.; Muderawan, W.; S. Ng. Synthesis and Application of Mono-6-(3-

Methylimidazolium)-6-Deoxyperphenylcarbamoyl-β-Cyclodextrin Chloride as Chiral

Stationary Phases for High-Performance Liquid Chromatography and Supercritical Fluid

Chromatography. J. Chromatogr. A 2008, 1182, 136–140.

Ong, T. T.; Tang, W.; Muderawan, W.; Ng, S. C.; Chan, H. S. O. Synthesis and Application of

Single-Isomer 6-Mono(alkylimidazolium)-β-Cyclodextrins as Chiral Selectors in Chiral

Capillary Electrophoresis. Electrophoresis 2005, 26, 3839–3848.

ACCEPTED MANUSCRIPT


Opallo, M.; Lesniewski, A. A Review on Electrodes Modified with Ionic Liquids. J. Electroanal.

Chem. 2011, 656 (1), 2–16.

Ping, W.; Xu, H.; Zhu, X. Separation/Analysis of Chrysophanol by Ionic Liquid Loaded β-

Cyclodextrin Polymer Coupled with Ultraviolet Spectrophotometry. Biochem. Anal.

Biochem. 2013, 2 (3), 1–5.

Ping, W.; Zhu, X.; Wang, B. An Ionic Liquid Loaded β-Cyclodextrin-Cross-Linked Polymer as

the Solid Phase Extraction Material Coupled with High-Performance Liquid

Chromatography for the Determination of Rhodamine B in Food. Anal. Lett. 2014, 47 (3),

504–516.

Pino, V.; Germán-Hernández, M.; Martín-Pérez, A.; Anderson, J. L. Ionic Liquid-Based

Surfactants in Separation Science. Sep. Sci. Technol. 2012, 47 (2), 264–276.

Podar, A.; Suciu, Ş. O. Ţ. A.; Oprean, R. Review – Recent Enantiomer Separation Strategies of

Nonsteroidal Anti-Inflammatory Drugs ( NSAIDS ) by Capillary Electrophoresis.

Farmacia 2016, 64 (2), 159–170.

Qi, S.; Cui, S.; Chen, X.; Hu, Z. Rapid and Sensitive Determination of Anthraquinones in

Chinese Herb Using 1-Butyl-3-Methylimidazolium-Based Ionic Liquid with β-

Cyclodextrin as Modifier in Capillary Zone Electrophoresis. J. Chromatogr. A 2004, 1059,

191–198.

Qi, S.; Zhang, H.; Zhu, J.; Chen, X.; Qi, L. Ionic Liquids as Modifiers to Improve the Separation

Efficiency of Nonaqueous Capillary Electrophoresis with High Electric Field Strengths.

ACCEPTED MANUSCRIPT


2014, No. 52, 460–465.

Qin, W.; Li, S. F. Y. Determination of Ammonium and Metal Ions by Capillary Electrophoresis-

Potential Gradient Detection Using Ionic Liquid as Background Electrolyte and Covalent

Coating Reagent. J. Chromatogr. A 2004, 1048, 253–256.

Qin, X.; Zhu, X. Determination of Allura Red in Food by Ionic Liquid SS-Cyclodextrin-Cross-

Linked Polymer Solid Phase Extraction and High-Performance Liquid Chromatograph.

Anal. Lett. 2016a, 49 (2), 189–199.

Qin, X.; Zhu, X. Ionic Liquid-β-Cyclodextrin Polymer for the Separation/analysis of

Lornoxicam. Supramol. Chem. 2016b, 278, 1–10.

Rahim, N. Y.; Mohamad, S.; Alias, Y.; Sarih, N. M. Extraction Behavior of Cu(II) Ion From

Chloride Medium to the Hydrophobic Ionic Liquids Using 1,10-Phenanthroline. Sep. Sci.

Technol. 2011, 47 (2), 250–255.

Rahim, N. Y.; Tay, K. S.; Mohamad, S. Chromatographic and Spectroscopic Studies on β-

Cyclodextrin Functionalized Ionic Liquid as Chiral Stationary Phase: Enantioseparation of

Flavonoids. Chromatographia 2016a, 79 (21–22), 1445–1455.

Rahim, N. Y.; Tay, K. S.; Mohamad, S. β-Cyclodextrin Functionalized Ionic Liquid as Chiral

Stationary Phase of High Performance Liquid Chromatography for Enantioseparation of β-

Blockers. J. Incl. Phenom. Macrocycl. Chem. 2016b, 85 (3–4), 303–315.

Ramo, Â.; Giordano, F.; Novak, C.; Caro, L.; Natura, D. R.; Vi, L. Thermal Analysis of

Cyclodextrins and Their Inclusion Compounds. 2001, 380, 123–151.

ACCEPTED MANUSCRIPT


Raoov, M.; Mohamad, S.; Abas, M. R. Removal of 2,4-Dichlorophenol Using Cyclodextrin-

Ionic Liquid Polymer as a Macroporous Material: Characterization, Adsorption Isotherm,

Kinetic Study, Thermodynamics. J. Hazard. Mater. 2013, 263, 501–516.

Raoov, M.; Mohamad, S.; Bin Abas, M. R.; Surikumaran, H. New Macroporous β-Cyclodextrin

Functionalized Ionic Liquid Polymer as an Adsorbent for Solid Phase Extraction with

Phenols. Talanta 2014a, 130, 155–163.

Raoov, M.; Mohamad, S.; Abas, M. R. Synthesis and Characterization of β-Cyclodextrin

Functionalized Ionic Liquid Polymer as a Macroporous Material for the Removal of

Phenols and As(V). Int. J. Mol. Sci. 2014b, 15, 100–119.

Sambasevam, K. P.; Mohamad, S.; Sarih, N. M.; Ismail, N. A. Synthesis and Characterization of

the Inclusion Complex of β-Cyclodextrin and Azomethine. Int. J. Mol. Sci. 2013, 14,

3671–3682.

Schneiderman, E.; Stalcup, A. M. Cyclodextrins: A Versatile Tool in Separation Science. J.

Chromatogr. B. Biomed. Sci. Appl. 2000, 745, 83–102.

Singh, R.; Bharti, N. Characterization of Cyclodextrin Inclusion Complexes—a Review. J.

Pharm. Sci. Technol. 2010, 2 (3), 171–183.

Sinniah, S.; Mohamad, S.; Manan, N. S. A. Magnetite Nanoparticles Coated with β-Cyclodextrin

Functionalized-Ionic Liquid: Synthesis and Its Preliminary Investigation as a New Sensing

Material. Appl. Surf. Sci. 2015, 357, 543–550.

Stalcup, a. M.; Cabovska, B. Ionic Liquids in Chromatography and Capillary Electrophoresis. J.

ACCEPTED MANUSCRIPT


Liq. Chromatogr. Relat. Technol. 2005, 27 (7–9), 1443–1459.

Surikumaran, H.; Mohamad, S.; Sarih, N. M. Molecular Imprinted Polymer of Methacrylic Acid

Functionalised β-Cyclodextrin for Selective Removal of 2,4-Dichlorophenol. Int. J. Mol.

Sci. 2014, 15, 6111–6136.

Tang, S.; Liu, S.; Guo, Y.; Liu, X.; Jiang, S. Recent Advances of Ionic Liquids and Polymeric

Ionic Liquids in Capillary Electrophoresis and Capillary Electrochromatography. J.

Chromatogr. A 2014, 1357, 147–157.

Tang, W.; Ong, T. T.; Ng, S.-C. Chiral Separation of Dansyl Amino Acids in Capillary

Electrophoresis Using Mono-(3-Methyl-Imidazolium)-Beta-Cyclodextrin Chloride as

Selector. J. Sep. Sci. 2007a, 30 (9), 1343–1349.

Tang, W.; Ong, T. T.; Muderawan, I. W.; Ng, S. C. Effect of Alkylimidazolium Substituents on

Enantioseparation Ability of Single-Isomer Alkylimidazolium-β-Cyclodextrin Derivatives

in Capillary Electrophoresis. Anal. Chim. Acta 2007b, 585, 227–233.

Tang, Y.; Zukowski, J.; Armstrong, D. W. Investigation on Enantiomeric Separations of

Fluorenylmethoxycarbonyl Amino Acids and Peptides by High-Performance Liquid

Chromatography Using Native Cyclodextrins as Chiral Stationary Phases. J. Chromatogr.

A 1996, 743, 261–271.

Tokalıoğlu, Ş.; Yavuz, E.; Şahan, H.; Çolak, S. G.; Ocakoğlu, K.; Kaçer, M.; Patat, Ş. Ionic

Liquid Coated Carbon Nanospheres as a New Adsorbent for Fast Solid Phase Extraction of

Trace Copper and Lead from Sea Water, Wastewater, Street Dust and Spice Samples.

ACCEPTED MANUSCRIPT


Talanta 2016, 159, 222–230.

Vaher, M.; Borissova, M.; Koel, M.; Kaljurand, M. Ionic Liquids as Background Electrolyte

Additives and Coating Materials in Capillary Electrophoresis. Proc. Est. Acad. Sci. Chem.

2007, 56, 187–198.

Vidal, L.; Riekkola, M. L.; Canals, A. Ionic Liquid-Modified Materials for Solid-Phase

Extraction and Separation: A Review. Anal. Chim. Acta 2012, 715, 19–41.

Wang, B.; He, J.; Bianchi, V.; Shamsi, S. A. Combined Use of Chiral Ionic Liquid and CD for

MEKC: Part II. Determination of Binding Constants. Electrophoresis 2009a, 30 (16),

2820–2828.

Wang, B.; He, J.; Bianchi, V.; Shamsi, S. A. Combined Use of Chiral Ionic Liquid and

Cyclodextrin for MEKC: Part I. Simultaneous Enantioseparation of Anionic Profens.

Electrophoresis 2009b, 30 (16), 2812–2819.

Wang, R.; Ong, T.; Ng, S. Synthesis of Cationic β -Cyclodextrin Derivatives and Their

Applications as Chiral Stationary Phases for High-Performance Liquid Chromatography

and Supercritical Fluid Chromatography. 2008, 1203, 185–192.

Wang, Y.; Han, J.; Liu, Y.; Wang, L.; Ni, L.; Tang, X. Recyclable Non-Ligand Dual Cloud Point

Extraction Method for Determination of Lead in Food Samples. Food Chem. 2016, 190,

1130–1136.

Yang, M.; Wu, X.; Xi, X.; Zhang, P.; Yang, X.; Lu, R.; Zhou, W.; Zhang, S.; Gao, H.; Li, J.

Using β-Cyclodextrin/attapulgite-Immobilized Ionic Liquid as Sorbent in Dispersive Solid-

ACCEPTED MANUSCRIPT


Phase Microextraction to Detect the Benzoylurea Insecticide Contents of Honey and Tea

Beverages. Food Chem. 2016, 197, 1064–1072.

Yu, X.; Chen, Y.; Chang, L.; Zhou, L.; Tang, F.; Wu, X. β-Cyclodextrin Non-Covalently

Modified Ionic Liquid-Based Carbon Paste Electrode as a Novel Voltammetric Sensor for

Specific Detection of Bisphenol A. Sensors Actuators, B Chem. 2013, 186, 648–656.

Zaijun, L.; Xiulan, S.; Junkang, L. Ionic Liquid as Novel Solvent for Extraction and Separation

in Analytical Chemistry. Ion. Liq. Appl. Perspect. 2011, 153–180.

Zain, N. N. M.; Raoov, M.; Abu Bakar, N. K.; Mohamad, S. Cyclodextrin Modified Ionic Liquid

Material as a Modifier for Cloud Point Extraction of Phenolic Compounds Using

Spectrophotometry. J. Incl. Phenom. Macrocycl. Chem. 2016, 84, 137–152.

Zhang, J.; Shen, X.; Chen, Q. Separation Processes in T He Presence of Cyclodextrins Using

Molecular Imprinting Technology and Ionic Liquid Cooperating Approach. 2011, 74–85.

Zhang, J.; Du, Y.; Zhang, Q.; Chen, J.; Xu, G.; Yu, T.; Hua, X. Investigation of the Synergistic

Effect with Amino Acid-Derived Chiral Ionic Liquids as Additives for Enantiomeric

Separation in Capillary Electrophoresis. J. Chromatogr. A 2013, 1316, 119–126.

Zhang, Y.; Yu, H.; Wu, Y.; Zhao, W.; Yang, M.; Jing, H.; Chen, A. Combined Use of [TBA][L-

ASP] and Hydroxypropyl-β-Cyclodextrin as Selectors for Separation of Cinchona

Alkaloids by Capillary Electrophoresis. Anal. Biochem. 2014, 462, 13–18.

Zhou, C.; Deng, J.; Shi, G.; Zhou, T. β -Cyclodextrin-Ionic Liquid Polymer Based Dynamically

Coating for Simultaneous Determination of Tetracyclines by Capillary Electrophoresis.

ACCEPTED MANUSCRIPT


Electrophoresis 2016, 1–20.

Zhou, N.; Zhu, X. S. Ionic Liquids Functionalized β-Cyclodextrin Polymer for

Separation/analysis of Magnolol. J. Pharm. Anal. 2014, 4 (4), 242–249.

Zhou, N.; Sang, R.; Zhu, X. Functionalized β -Cyclodextrin Polymer Solid Phase Extraction

Coupled with UV – Visible Spectrophotometry for Analysis of Kaempferol in Food

Samples. Food Anal.Methods 2014, 7, 1256–1262.

Zhou, Z.; Li, X.; Chen, X.; Hao, X. Synthesis of Ionic Liquids Functionalized β-Cyclodextrin-

Bonded Chiral Stationary Phases and Their Applications in High-Performance Liquid

Chromatography. Anal. Chim. Acta 2010, 678, 208–214.

ACCEPTED MANUSCRIPT


Table 1 CD-IL modified materials in CE

IL CD Analytes Sample BGE/Buffer Ref.

1-hexyl-3-methylimidazolium

(HMIM)

α-

cyclodextrin

metal ions and

ammonium

standard

stock

solution

7.5mM lactic

acid, 0.6mM 18-

crown-6, 12mM

α-CD at pH 4.0

(Qin and

Li, 2004)

6-O-2

hydroxpropyltrimethylammonium

tetrafluoroborate

β-

cyclodextrin

Bifonazole

brompheniramine

chlorpheniramine,

liarozole pheniramine,

promethazine,

tropicamide, warfarin

eight racemic

drugs

NaH2PO4 (pH

2.5-5.0)

(Jia Yu,

Lihua

Zuo,

Hongjiao

Liu,

Lijuan

Zhang,

2013)

Ethyl and phenylcholine of

bis(trifluoromethylsulfonyl)imide

Di or

trimethyl-β-

cyclodextrin

2-arylpropionic acids anti-

inflammatory

drugs

Acetic

acid/sodium

acetate (5mM

and 6mM) at pH

5.0

(François

et al.,

2007)

1-butyl-3-methylimidazolium

tetrafluoroborate

β-

cyclodextrin

anthraquinones chinese Herb

Paedicalyx

attopervensis

Pierre ex

Pitard

1B-3-MI-TFB

[20-80mM] and

β-CD [1-6mM]

(Qi et al.,

2004)

ACCEPTED MANUSCRIPT


N-undecenoxycarbonyl-L-

leucinol bromide (L-UCLB)

2,3,6-tri-o-

methyl-β-

cyclodextrin

ibuprofen, fenoprofen,

indoprofen, suprofen,

and ketoprofen

standard

solution

35 mM TM-β-

CD, 5 mM

sodium acetate at

pH 5.0

(Wang et

al.,

2009b)

N-undecenoxycarbonyl-L-

leucinol bromide (L-UCLB)

2,3,6-tri-o-

methyl-β-

cyclodextrin

ibuprofen, fenoprofen,

indoprofen, suprofen,

and ketoprofen

standard

solution

5mM NaOAc at

pH 5.0 with TM-

β-CD and

without TM-β-

CD

(Wang et

al.,

2009a)

L-alanine and L-valinetert butyl

ester bis (trifluoromethane)

sulfonimide

Me-β-CD,

HP-β-CD,

and Glu-β-

CD

naproxen,

pranoprofen,warfarin,

carprofen, ibuprofen

and ketoprofen

standard

solution

30mM sodium

citrate/citric acid

buffer containing

organic modifier

(20%v/v)

(Zhang

et al.,

2013)

Chiral ionic liquid ([TBA][L-

ASP])

HP-β-CD quinine/quinidine and

cinchonine/cinchonidine

cinchona

alkaloids

40mM

ammonium

acetate with

NaOH and acetic

acid at pH 3.5-

5.5

(Zhang

et al.,

2014)

3-methylimidazolium chloride β-CD dansyl amino acids standard

solution

50 mM of

NaH2PO4 titrated

with NaOH or

H3PO4 at pH

(6.5–9.6)

(Tang et

al.,

2007a)

ACCEPTED MANUSCRIPT


alkylimidazolium chloride where

alkyl= methyl, ethyl, propyl,

butyl, and hexyl

β-CD dansyl amino acid standard

solution

50 mM acetic

acid in deionized

water at pH 5.0

and 6.0

(Tang et

al.,

2007b)

alkylimidazolium chlorides where

alkyl= methyl, butyl, decyl, 1,2-

dimethyl

β-CD dansyl amino acid standard

solution

acid BGE at pH

6.0 and basic

BGE at pH 9.6

phosphate/acetate

buffer

(Ong et

al.,

2005)

1-methylimidazole (MIM) β-CD Doxycycline,

Tetracycline,

oxytertracycline,

chlortetracycline

water

samples

10 mmol/L at pH

7.2 Na2HPO4-

KH2PO4

(Zhou et

al.,

2016)

ACCEPTED MANUSCRIPT


Table 2 CD-IL modified materials as chiral stationary phases in HPLC

IL CD Analytes Mobile Phase Ref.

1,2-dimethylimidazole β-cyclodextrin

two racemic

drugs and

sixteen

chiral

aromatic

alcohol

derivatives

Acetonitrile/methanol/acetic

acid/triethylamine (a)

480/20/1/1, (b) 480/20/1/2

(c) 480/20/2/1(v/v)

(Zhou

et al.,

2010)

1-methylimidazolium chloride deoxyperphenylcarbamoyl-

β-cyclodextrin

10 racemic

derivatives

of aromatic

alcohols

n-hexane/2-propanol (97/3,

v/v)

(Ong

et al.,

2008)

Methylimidazole and n-

octylimidazole β-cyclodextrin

18 racemic

aryl alcohols

Mixture of hexane and 2-

propanol

(Wang

et al.,

2008)

ACCEPTED MANUSCRIPT


Mono-6-deoxy-6-(p-N,N,N-

trimethylaminobenzimide),mono-

6-deoxy-6-(p-N-

methylimidazolemethylbenzimide)

Benzimido-β-cyclodextrin

chiral 1-

phenyl-2-

nitroethanol

derivatives,

aromatic

alcohols and

ferrocene

a)50:50 methanol/water

b)40:60 methanol/water

(Li and

Zhou,

2014)

3-benzylimidazolium tosylate β-cyclodextrin

β-blockers

(propranolol,

metoprolol,

pindolol,

and atenolol)

Methanol with

water/acetonitrile (1/1, v/v)

(Rahim

et al.,

2016b)

ACCEPTED MANUSCRIPT


1-benzylimidazole β-cyclodextrin

Flavonoids

(Flavanone,

Hesperetin,

Naringenin,

Eriordictoyl

ACN/water and

MeOH/water 1)50/50

2)90/10

(Rahim

et al.,

2016a)

ACCEPTED MANUSCRIPT


Table 3 β-CD-IL modified materials as cross-linked polymer sorbents in SPE

IL CD Elution

Condition Analytes Sample Recoveries Ref.

Methyl imidazolium,

butyl imidazolium,

pyridinium

β-

cyclodextrin NIL

2,4,6-

trichlorophenol

(TCP), para-

nitrophenol (PNP),

and Cr6+

Drinking

water

samples

β-

CDMIMOTs/TDI:

77% β-

CDMIMOTs/HDI:

80%

(Malefetse

et al.,

2009)

1-benzylimidazole β-

cyclodextrin 2mL MeOH phenols

water

samples 87.0-116.0%

(Raoov et

al., 2014a)

α-picoline-based

ionic liquid

β-

cyclodextrin HCI Mn(VII)andMn(II)

water

samples 86.5-113.2%

(Chen et

al., 2016)

Hydrophobic ionic

liquids [C4min] PF 6

β-

cyclodextrin 4mL EtOH Chrysophanol pills/tablets 98.13-98.32%

(Ping et

al., 2013)

1,2-dimethyl

imidazole

β-

cyclodextrin 5mL MeOH Magnolol

drug

samples 93.4%

(Zhou and

Zhu, 2014)

Imidazole β-

cyclodextrin 6mL MeOH Kaempferol

food

samples 85.0%

(Zhou et

al., 2014)

ACCEPTED MANUSCRIPT


α-picoline-based

ionic liquid

β-

cyclodextrin 4mL MeOH Lornoxicam

blood

samples 95.5-108.0%

(Qin and

Zhu,

2016b)

α-picoline-based

ionic liquid

β-

cyclodextrin

5mL

EtOH/NH3/H2O Allura Red

food

samples 96.0 -112.0%

(Qin and

Zhu,

2016a)

1-hexyl-3-

methylimidazolium

hexafluorophosphate

β-

cyclodextrin 4mL EtOH Rhodamine B

food

sample

99.3%-102.2% in

Chilli 100.5% and

100.8% in hot

pepper

(Ping et

al., 2014)

1-hexyl-3-

methylimidazolium

hexafluorophosphate

β-

cyclodextrin 4mL EtOH Linuron

fruit and

vegetable

samples

92.0-104.0% (Feng et

al., 2015)

ACCEPTED MANUSCRIPT


Table 4 CD-IL as electrode modifier in electrochemical sensor

Electrode Modifier Analytes Limit of Detection

/Sensitivity Ref.

β-CD-BMIMBF4/GCE Quercetin

and H2O2 0.067 μM (Cao et al., 2011)

β-CD-MIM/GCE Bisphenol A Electrochemical potential

at 0.5V (Sinniah et al., 2015)

β-CD-BIM/CPE

2,4-

dichlorophen

ol (2,4-DCP)

720 mV with the

oxidation peak current at

1.28 μA

(Mohamad et al.,

2015)

β-CD-BMIMBF4/CPE Bisphenol A 8.3 ×10-8

mol L-1

(Yu et al., 2013)

β-CD-BIM-/CPE

2,4-

dichlorophen

ol (2,4-DCP)

1.2 mmol L-1

(Mohd Rasdi et al.,

2016)

ACCEPTED MANUSCRIPT


Figure 1.1. Formation of CD-IL complex through (a) functionalization process (b) loading

process

ACCEPTED MANUSCRIPT


Figure 2.1. Interaction behaviour between anionic analyte, A-, chiral IL

+ cation and β-CD

derivatives

ACCEPTED MANUSCRIPT


Figure 2.2. Separation mechanism of the anthraquinones using 1-butyl-3-

methylimidazolium-based ionic liquid and β-CD

ACCEPTED MANUSCRIPT


Figure 2.3. The effects of additives in BGE on separation (a) 0, (b) 20 mmol/L β-CD, (c) 20

mmol/L β-CD-IL. Peaks: (1) doxycycline; (2) tetracycline; (3) oxytertracycline; and (4)

chlortetracycline. Experiment conditions: running buffer, 10 mmol/L pH 7.2 Na2HPO4-KH2PO4;

capillary: 65 cm , od: 360 μm, id: 75 μm; injection time: 10 s; separation voltage 15 kV;

Detection potential: 1.0 V. (Zhou et al., 2016)

ACCEPTED MANUSCRIPT


Figure 2.4. Schematic illustration of MSPE process

perspectives in analytical chemistry: current and future ... · pdf fileanalytical...

Documents