Supramolecular Liquid Crystals Based on Cyclodextrins

Abstract

Cyclodextrin-based materials represent an environmentally friendly alternative to toxic liquid crystalline materials. Cyclodextrins are well-known for their cavity and inclusion properties. They are scaffold molecules that can be chemically modified to obtain functional materials for various applications. For instance, amphiphilic cyclodextrins have attracted tremendous interests from researchers of different fields because of their ability to self-assemble and to encapsulate medicines. They can also be designed to form supramolecular liquid crystals. Since the first report of a class of 6-alkylthiolated β-cyclodextrin derivatives that exhibit thermotropic liquid crystalline properties in 1993, there has been only few developments in this area. But there is an increasing interest to develop cyclodextrin-based liquid crystalline materials, owing to their potential utilities in different areas.

In this chapter, we review cyclodextrins-based molecular designs, their synthesis, as well as characterization of their thermotropic and lyotropic liquid crystalline properties. The presence of numerous hydroxyl groups and a face-to-face pseudo-symmetry in native cyclodextrins create numerous opportunities for the design of smart materials. It has been shown that not only the nature of the substituent, but also its location highly influences the self-assembly behavior of the cyclodextrin derivatives. After an introduction on cyclodextrins and liquid crystals, we summarize various approaches used to chemically modify cyclodextrins for the development of thermotropic and lyotropic liquid crystals, such as generating amphiphilic derivatives, or appending mesogenic groups to both monomeric and polymeric cyclodextrin backbones. The last section presents examples of applications of cyclodexrin-based liquid crystals for bio-sensing and liquid crystal displays.

7.1 Introduction

7.1.1 Cyclodextrins Structures

Cyclodextrins (CDs) are polyhydroxylated macrocycles based on D-glucose. The three most commonly encountered members are α-, β- and γ-CDs which contain 6, 7 and 8 D-glucopyranosyl units, respectively giving birth to a characteristic truncated cone-shaped cavity of different sizes (Fig. 7.1).^,

Fig. 7.1

Graphical representation of the three most commonly encountered cyclodextrins; α, β, and γ cyclodextrins

The inner cavity volume of these cyclodextrins vary between 0.17–0.42 nm³ and their diameters from 0.49 to 0.79 nm. The cavities of cyclodextrins are relatively hydrophobic compared to outer surface, which provides them with ability to form inclusion complexes with organic guest molecules that are characterized with improved water-solubility, air-stability, reduced tissue-irritability, and other benefits. The electrochemical potential map of β-cyclodextrin shown in Fig. 7.2 , greatly represents the hydrophobic character of cyclodextrins cavity. The red, blue and green colors illustrate the negative, positive, and neutral electrochemical regions, respectively. Such representation emphasizes the contrast between the hydrophobic inner cavity and hydrophilic outer-surface of cyclodextrins.

Fig. 7.2

Electrochemical potential map of the truncated cone-shaped structure of β- cyclodextrin

For these reasons, cyclodextrins have attracted considerable attention from pharmaceutical and other industries (Hirayama and Uekama 1999; Rasheed 2008). Structurally, the D-glucose units are linked together via α(1,4)-glycosidic linkages, which arranges all the primary hydroxyl groups (OH-6’s) at the narrower face (primary face) of the cavity, and all the secondary hydroxyl groups (OH-2’s and OH-3’s) at the wider face (secondary face) (Fig. 7.3).

Fig. 7.3

Commonly used nomenclature for hydrogens in native cyclodextrins as well as their axial symmetry and face to face pseudosymmetries

Consequently, all cyclodextrins possess an axial symmetry, as well as a face-to-face pseudo symmetry. Although cyclodextrins improve aqueous solubility of hydrophobic molecules, they are unfortunately restrained by their own solubility in aqueous media. α, β, and γ- cyclodextrins have a water solubility of 14.5%, 1.85%, and 23.2% (w/v) respectively at room temperature (Davis and Brewster 2004). Their lower solubility is partly attributed to the intramolecular hydrogen bond network which lessens their ability to form H-bonding with water molecules (Rasheed 2008). Enhanced solubility can be achieved by reducing the strength of this network. For instance, partial methylations of cyclodextrins have shown to increase water-solubility tremendously (Rasheed 2008). Because of their high polarity, native cyclodextrins also have very limited solubility in most organic solvents. To expand their applications in pharmaceutical industries, various chemical modifications have been developed. The three most widely used and commercially viable strategies are to partially alkylate the β-cyclodextrin scaffold with methyl, 2-hydroxypropyl, or sulfobutyl groups, to afford respectively RMβ-CD, HPβ-CD and SBEβ-CD (Fig. 7.4). Unfortunately, due to coexistence of multiple types of hydroxyl groups and limited differences in their reactivity, all chemically modified cyclodextrin derivatives available on the market are sold as mixtures that contain different degrees of substitutions (Rasheed 2008).

Fig. 7.4

Structures of commercially available CD derivatives; randomly methyl-β-cyclodextrin (RMβ-CD), 2-hydroxypropyl β-CD (HPβCD), and sulfobutyl ether (SBEβ-CD)

7.1.2 Cyclodextrin Modifications

At first sight, since the hydroxyl groups are the only available functional group present at the two rims of the cavity, one might believe cyclodextrin chemical modifications to be simple but they are in fact very challenging, due to their presence in large number. Three types of hydroxyl groups can be identified within a native cyclodextrin molecule: those respectively attached to 2, 3, and 6-positions of glucopyranosyl units (Szejtli and Huber 2012). In the case of β-cyclodextrin, each type of hydroxyl groups consists of 7 identical copies. Due to the circular geometry, the hydroxyl groups of the seven glucose moieties form an intramolecular H-bonding network, resulting in a relatively rigid structure. At the primary face, the primary hydroxyl groups attached to the 6 positions have an additional degree of rotational freedom, making the hydrogen bond network weaker. More importantly, they experience lower steric hindrance, resulting in higher reactivity (Khan et al. 1998). On the other hand, all secondary hydroxyl groups located at the 2- and 3-positions experience reduced rotational freedom allowing the formation of a stronger hydrogen bond network. Furthermore, the increase in steric hindrance contributes to their lower reactivity.

X-ray experiments revealed that the OH-3 groups act as H-bond donors while the OH-2 as H-bond acceptors; this makes OH-2’s the most acidic (Saenger et al. 1976). Since the protons of OH-3 groups are involved in intramolecular hydrogen bonding, they are generally less reactive, thus most challenging to modify. Consequently, by controlling the reactivity of the chemical reagent used, one can achieve regioselective modification of cyclodextrins. For instance, the OH-6’s can be selectively protected with bulky groups such as tert-butyldimethylsilyl, while less bulky group such as trimethysilyl can be introduced to all 3 positions (Cramer et al. 1969; Takeo et al. 1988). The most acidic OH-2 groups can be deprotonated first to allow selective OH-2 monoalkylation. However, the proton exchange between the OH-2 and OH-6 positions often reduces the regioselectivity which produces mixtures of O2- and O6-substituted derivatives (Khan et al. 1998).

Since cyclodextrins possess the capability to form complexes, it is possible in few cases to achieve regioselective modifications by taking advantage of their inclusion properties (Ueno and Breslow 1982). This process is greatly influenced by the solvent effect and the size of the substituted cyclodextrin cavity. For instance, the 6-tosylated-α-cyclodextrin product is obtained in pyridine, while the reaction in aqueous media yields the mono-2-tosylate α-cyclodextrin. On the other hand, if β-cyclodextrin is subjected to a monotosylation in water, the 6-tosylate is obtained (Fujita et al. 1984).

In general, since the OH-6’s in cyclodextrins are the most nucleophilic and least sterically hindered, per-substitutions at the primary face are less troublesome. On the other hand, since all primary hydroxyl groups have identical chemical reactivities, partial substitutions such as mono-, di-, and tri-substitutions are usually much more challenging, as they usually lead to the formation of many regioisomers (also referred to as positional isomers) which are extremely difficult to separate. Consequently, partial substitutions usually result in low yields of the desired product.

Persubsitutions at the secondary face are especially difficult because of the inherited lower chemical reactivity of secondary hydroxyl groups. Moreover, there are twice the amounts of –OH groups at the secondary face compared to primary face; as the reaction progresses, the reactive sites become increasingly more hindered, making the approach of electrophiles more challenging.

7.1.3 Synthesis of Amphiphilic Cyclodextrins

The face-to-face pseudosymmetry (Zhang et al. 1992) can be taken advantage of by chemical modifications, to introduce hydrophobic groups to only one face of the molecule. This results in the formation of amphiphilic molecules. These amphiphilic cyclodextrins act like detergent in water, thus possess the ability to form self-assembled systems (Bonini et al. 2006). Depending on the size and geometry of the introduced hydrophobic groups, different nano-materials can be obtained through their self-assembly (Nagarajan 2002) such as spherical micelles, liposomes and other rod-like objects (Nagarajan 2002). Once assembled into such self-organized structures, the inherent cyclodextrin cavity and the hydrophobic regions found within the apolar chains can be used to host the hydrophobic guest molecules, creating efficient drug delivery systems for the treatment of disease. This has attracted considerable interest from pharmaceutical researchers (Rajewski and Stella 1996; Challa et al. 2005; Hoare and Kohane 2008). Such amphiphilic systems are advantageous compared to non-amphiphilic cyclodextrins which can only encapsulate the desired cargo into the hydrophobic cyclodextrin cavity, for enhanced distribution of drug to the disease model. By forming self-assembled nanostructures, a concentrating effect may be achieved, with many replicas of the drug trapped in one nanostructure. Upon administration, self-assembled nanoparticles can reach the targeted disease cells, and deliver replicas of drug molecules at the same time, thus augmenting the therapeutic potency and efficacy (Yallapu et al. 2010). Consequently, this could greatly improve drug safety while reducing toxicity, as lower dosage could be administered without diminishing the overall therapeutic effect of the medicine (Rajewski and Stella 1996).

Amphiphilic cyclodextrin complexes can be designed to control the average release rate of a drug. In fact, cyclodextrins have been modified to offer a desired drug-releasing mechanism to improve the oral bioavailability of steroids, cardiac glycosides, non-steroidal anti-inflammatory drugs, benzodiazepines etc. (Rasheed 2008). For instance, when a drug has to be delivered to the enteric region, a delayed release is required to prevent premature leaking of the cargo into the stomach, which presents a harsh acidic environment. In order to reach the upper small intestine, a cyclodextrin-based drug delivery system (DDS) bearing weak acidic groups at its surface was designed. Such formulations display reduced solubility in the stomach while increased solubility in neutral and alkaline regions, owing to ionization of the acidic groups. This pH dependent behavior allows a delayed release of the drug into the enteric region. As an example, 6-O-(carboxymethyl)-β-cyclodextrin derivatives have been developed as a drug delivery system for time-controlled release of oral medicine; the system exhibited restricted solubility in acidic conditions but improved solubility with increasing pH (Uekama 2004).

7.1.4 Liquid Crystals

Self-assembly of simple systems into well-ordered nano-structures is a fascinating topic. The understanding of the fundamentals of soft-matter self-organization has stimulated tremendous research interest throughout the last decade (Hoeben et al. 2005; Yagai and Kitamura 2008). Liquid crystal represents a state of the matter between solid and liquid phase. It displays the fluidity of liquids while possessing the molecular alignment of crystalline solid. Liquid crystalline phases are referred to as mesophases and the molecules responsible for such behavior, as mesogens. In order to obtain spontaneous self-assembly of specific material into highly-ordered molecular structures at nanoscales, molecular building blocks must be precisely engineered to display the desired characteristics. In an attempt to improve our understanding of such phenomena, some background information about the transitions from crystalline solid to isotropic liquid will be discussed.

Commonly, two main parameters are used to report molecular arrangement in different phases, the orientational order which describes the alignment of molecules to a director (n), and the positional order which refers to the center of mass of each molecule with respect to each other. A material in crystalline solid phase is composed of molecules having both positional and orientational order with periodically repeating patterns. Such nanoscale organization is possible because of non-covalent intermolecular forces. Within the crystalline phase, the sole movement of the molecules is the thermal vibration within the crystal lattice (Gray 1962). As the temperature increases, these vibrations become stronger and eventually overcome the intermolecular interactions. At the transition temperature (melting), the solid material enters an isotropic liquid phase. It can be rationalized that at such temperature, the long range positional order is destroyed, providing freedom to the molecules for random traveling.

On the other hand, some materials possess liquid crystalline phases, associated with transitions observed between the crystalline and isotropic liquid phases, characterized by the presence of either positional or orientational order or both. Higher degrees of orientational order give the mesophase enhanced anisotropic properties while lower degrees of positional order provide greater fluidity (McArdle 1990).

Liquid crystals are classified into two main families: thermotropic and lyotropic. Thermotropic liquid crystals are formed from pure products which self-organize into mesophases upon temperature variation. In contrast, lyotropic liquid crystals are formed by the addition of solvent to an amphiphilic molecule, resulting in long range positional orders due to the self-organization properties of the molecule.

Throughout this chapter several examples of cyclodextrin-based liquid crystal designs will be discussed. First, cyclodextrin-based thermotropic liquid crystals will be presented and rationalized based on the interactions and substituents responsible for their self-assembly. In the second section, lyotropic liquid crystalline systems containing cyclodextrins will be discussed, as well as some of their potential applications.

7.1.5 Thermotropic Liquid Crystals

Thermotropic liquid crystals are materials whose self-assembly behavior is influenced by temperature variation in the solid states. They can exist in many different phases. The three most common phases are: nematic (Fig. 7.5), smectic (Fig. 7.6) and discotic (Fig. 7.7) liquid crystalline phases.

Fig. 7.5

Pictogram representation of molecular arrangement in the nematic liquid crystalline mesophases

Fig. 7.6

Pictogram representations of molecular arrangement in the smectic A, B, and C liquid crystalline mesophases

Fig. 7.7

Pictogram representations of molecular arrangement in the discotic liquid crystalline mesophases

7.1.5.1 Nematic Phase

The nematic phase (N) is the thermotropic liquid crystalline phase with the least order. This phase is characterized by self-organization of molecules into ordered structures in which the long axis of all molecules (director n) aligns with each other, procuring orientational order to the material. However, no positional order is found in nematic liquid crystalline phase since the center of mass of the molecules is isotropically distributed (Linlin et al. 2015).

7.1.5.2 Smectic Phases

Smectic mesophases are often observed when decreasing the temperature of nematic phase. They possess some degree of positional order in addition to the orientational order. The center of mass of the molecules aligns more or less with each other, forming layered structures (Collings and Hird 1997). Within the same layer, the molecules can move around, gain some degree of freedom but overall all molecules maintain a degree of translational order. Several types of smectic phases are known depending on the type and degree of order (Fig. 7.6). The least ordered smectic mesophase is called Smectic A (Sm A). Sm A mesophases consist of layered structures in which the director n is parallel to the layer normal but possess no order within the layers. Other smectic mesophases, such as Smectic C, differ from Smectic A by the tilted angle of their director n, with respect to the layer normal. Several other smectic mesophases are also known such as Smectic B, I, and F, which are generally characterized by the intra-layer short range positional order. They are also referred to as hexatic smectic phases. Within these phases, the center of mass of the molecules arranges in hexagonal pattern. The three different hexatic smectic phases (Sm B, Sm I, Sm F) differ in their respective director n orientation. Sm B director n aligns parallel to the layer normal, while in the case of Sm I, n is tilted towards the corner of the hexagon (apex), contrasting with Sm F whose director n is tilted towards the side of the hexagon.

7.1.5.3 Discotic Liquid Crystal

Discotic mesophases are usually formed by disk-shaped molecules which orient themselves in a layer-like fashion and packed into stacks (called discotic columns, Fig. 7.7). Similarly to smectic mesophases, the columns formed can possess random or ordered positions by arranging themselves into cubic or hexagonal arrays (Kumar 2010).

7.1.6 Lyotropic Liquid Crystals

Lyotropic liquid crystals, consist of two-component systems mostly displayed by amphiphilic molecules in solvent producing ordered mesophases (Hiltrop 1994). Lyotropic liquid crystals morphologies are highly dependent on concentration and temperature of the amphiphilic systems bearing hydrophilic head and hydrophobic tail (Tolédano and Neto 1998). At critical micelle concentration (CMC) in aqueous solutions, amphiphilic molecules aggregate into micelles with polar head groups directed outward and hydrophobic tails inward. Upon increasing the concentrations, the micelles can fuse to each other forming various types of lyotropic liquid crystals such as cubic micelles, hexagonal phase, cubic phase and lamellar bilayer phases. The lamellar phase consists of amphiphilic molecules arranged in bilayer structures (Fig. 7.8A). The non-polar tails of two oppositely directed molecules are intertwined into the inner membrane and polar head groups found at the surface. The bilayer structures resulting from this self-assembly are separated by layers of water at the interface. Generally, lamellar lyotropic liquid crystal phases are obtained in solution of amphiphilic molecules concentrations higher than 50%.

Fig. 7.8

Various types of lyotropic liquid crystals; (A) Lamellar, (B) Hexagonal, and (C) Cubic

In hexagonal phase, micelles are fused together; forming long ranged hexagonal cylinder arrays that exhibit birefringent textures (Fig. 7.8B). The distance between adjacent micellar cylinders is approximately 1 to 5 nm depending upon the concentration of amphiphilic and solvent molecules. Typically, hexagonal lyotropic liquid crystals are highly viscous with water content of 30 to 60% by weight. Cubic lyotropic liquid crystal phase, on the other hand, shows cubical arrangements of micelles that lead to viscous isotropic phases (Fig. 7.1C).

7.2 Cyclodextrin-Based Thermotropic Liquid Crystals

In the following section, several cyclodextrin-based thermotropic liquid crystals will be discussed. Based on their designs, they can be classified into three families: (a) cyclodextrin liquid crystalline systems that combine simple aliphatic chains and polar groups; (b) cyclodextrin liquid crystals that have incorporated mesogenic groups; (c) polymer-based cyclodextrin liquid crystals.

7.2.1 Thermotropic Liquid Crystals Based on Simple Amphiphilic Cyclodextrin Derivatives

7.2.1.1 H-Bond Mediated Mesophase Formation Based on Amphiphilic Cyclodextrin Derivatives

The early generations of amphiphilic cyclodextrin derivatives were prepared by introducing hydrophobic alkyl groups such as alkylamino, alkylthio, or alkylsulfonyl to the primary face of β-cyclodextrin. (Tanaka et al. 1987; Taneva et al. 1989). Unfortunately, these derivatives were a commonly prepared via the “per-6-tosylate of β-CD” through S_N2 substitutions. It was later found that the “per-6-tosylate of β-cyclodextrin” could only be isolated in pure form and in low yields by repeated high-performance liquid chromatography using reversed phase C18 column. This confirmed that the amphiphilic cyclodextrins prepared earlier were impure as they contained mixtures with different degrees of substitutions. (Ashton et al. 1991) Despite the heterogeneity in these materials, they were found to possess excellent properties in self-assembly such as forming mono-layer and Langmuir-Blodgett films at the water-air interface, micelles and liposomes in water etc. However, their thermotropic properties remained unknown until 1993 when Ling and Darcy (Ling et al. 1993) published the first series of cyclodextrin-amphiphiles that showed thermotropic liquid crystalline properties. Their successful synthesis began with the use of per-6-bromo-6-deoxy-β-cyclodextrin, which was prepared from native β-cyclodextrin 1 using Gadelle and Defaye’s protocol (Gadelle et al. 1991) which employs Br₂/Ph₃P as a reagent in anhydrous dimethylformamide. This afforded the per-6-deoxy-6-bromo-β-cyclodextrin 2 in excellent regioselectivity and high purity. The subsequent per-substitution by alkylthiolate of different lengths allowed them to synthesize per-6-alkylthio-substituted amphiphilic β-cyclodextrin derivatives 3a-e in excellent yields (>90%) and purities (Fig. 7.9).

Fig. 7.9

Synthetic scheme of the first family of amphiphilic cyclodextrins that displayed mesogenic properties

The incorporated chain lengths varied from C₂-C₁₈, which provided them opportunities to comprehensively study the thermotropic properties of this family of amphiphilic cyclodextrins. Both cross-polarized optical microscopy (POM) and differential scanning calorimetry (DSC) were used to determine the phase transitions of the materials upon heating and cooling, and cross-polarized optical microscopy further provided information on the birefringence of the material during phase transitions and formed textures. It was discovered that although all synthesized compounds showed some degrees of thermotropic liquid crystallinity, compounds 3d and 3e that contain chain lengths of 16 and 18 carbons respectively, displayed the best mesogenic properties over a wide temperature range (215 to 280 °C). However, upon heating further, both compounds decomposed before reaching their isotropic liquid phase. By comparing the textures of the two cyclodextrin compounds to monosaccharide mesogens bearing a single chain, the authors assigned the formed mesophases by compounds 3d and 3e to be smectic; thus, bilayer structures were proposed in the formed liquid crystalline phases. When analyzed by X-ray powder diffraction, derivative 3e revealed a sharp peak in the low angle region which was attributed to a bilayer depth of 38 Å, less than twice the calculated molecular length. The authors suggested that the CD molecules may exist at some degrees of inclination in the layers. In the later work, Ling and co-workers (Ward et al. 2014) explained the results using an interdigitation model by the amphiphilic CD molecules in the bilayer (Fig. 7.10).

Fig. 7.10

Schematic structures of synthesized β-cyclodextrin derivatives exhibiting thermotropic liquid crystal properties by Ling et al.

H-bonding was believed to be the major intermolecular force that drives the amphiphilic cyclodextrin molecules to self-assemble into highly ordered liquid crystalline mesophases. Because of their cyclic bidimensional geometry, amphiphilic cyclodextrin molecules can establish complex inter- and intra-molecular H-bond network in solid state. To elucidate the important role that H-bond played during the molecular self-assembling, Ling and co-workers (Ward et al. 2014) prepared a series of per-6-substituted β-cyclodextrin derivatives (4–9), all modified with the n-octadecylthio group at the 6-positions (Fig. 7.11).

Fig. 7.11

Synthesized per-6-substituted β-cyclodextrin derivatives containing n-octadecylthio groups

Compounds 4 and 5 were per-substituted at all O2 and O3 positions with methyl and benzyl groups respectively, thus they contained no hydroxyl groups, therefore were incapable of inducing molecular self-assembly via H-bonding in solid state. However, in principle, molecules of compound 5 could interact with each other via π-π interaction in solid state because of their phenyl groups. Compounds 6–9 are all amphiphilic as they were regioselectively modified at all O2 positions with alkyl groups, namely methyl 6, ethyl 7, allyl 8 or benzyl 9, but all possess seven hydroxyl groups (OH-3’s). Thus, all compounds 6–9 should be capable of intermolecular H-bonding in solid state. On the other hand, since the alkyl groups at O2 position increase in size from 6 to 9, their physical dimensions could effectively determine how close the molecules in the bilayers could get to each other in solid state. Logically, the ability to engage intermolecular H-bonding network in solid state should decrease from compounds 6 to 9.

Compound 4 was synthesized by first mesylating the per-2,3-di-O-methylated β-cyclodextrin 10 in a mixture of anhydrous pyridine-dichloromethane to obtain desired per-6-mesylate 11 in 95% yield. Subsequent nucleophilic substitutions of the 6-mesylates with potassium n-octadecylalkylthiolate, generated in situ by mixing n-octadecylalkylthiol with potassium tert-butoxide (KOBu-t) in THF afforded the desired β-cyclodextrin derivative 4 in 40% yield. The synthesis of the analogous compound 5 started from the per-2,3,6-O-benzylated compound 12, which was first subjected to an acetolysis at −60 °C in acetic anhydride using trimethylsilyl trifluoromethanesulfonate (TMSOTf) as the catalyst; this elegantly converted the less sterically hindered 6-O-benzyl groups to the corresponding 6-O-acetates in a highly regioselective manner to afford compound 13 (78%). Subsequent Zemplén O-transesterification in anhydrous methanol-tetrahydrofuran mixture using sodium methoxide as a catalyst, produced the heptol 14 quantitatively. Compound 14 was then activated in a similarly manner as compound 11 to afford the per-6-mesylate 15 (90%, yield), which was ultimately converted to target compound 5 (76% yield).

Compound 6 was synthesized by reacting a per-2,6-di-O-silylated derivative of β-cyclodextrin 16 with methyl iodide in the presence of sodium hydride in anhydrous dimethylformamide (Fig. 7.12) (Fügedi 1989). After the deprotonation, the O2-silyl groups underwent a clean migration to O3-positions of β-cyclodextrin, which provided the opportunity for O2 to be methylated under Williamson etherification conditions. The corresponding compound 17 was isolated in 60% yield (Ashton et al. 1995). The protecting tert-butyldimethylsilyl groups were then removed using tetra-n-butylammonium fluoride (TBAF) to obtain polyhydroxylated β-cyclodextrin 18 (87% yield). A regioselective per-6-iodination was then performed using I₂/PPh₃ as a reagent to afford the corresponding per-6-iodide 19 in 40% yield. Finally, all the 6-iodides were substituted by n-octadecylthiolate to provide the desired β-cyclodextrin derivative 6 in 64% yield (Fig. 7.13).

Fig. 7.12

Schematic synthesis of per-6-octadecylthiolated β-cyclodextrin derivatives 4 and 5

Fig. 7.13

Synthetic scheme of per-6-n-octadecylthio-2-O-methyl-β-cyclodextrin derivative 6

The remaining three compounds 7, 8 and 9 were synthesized according to Fig. 7.14 using compound 20 as a common starting material. First, a regioselective O2-alkylation was performed using NaH as a base, and either ethyl iodide, or allyl bromide or benzyl bromide as an electrophile. The corresponding intermediates 21–23 were obtained in 30–52% yields. Then the 6-O-tert-butyldimethylsiloxy groups were directly converted to the corresponding 6-bromide using homologuous brominating conditions as reported for 19 (bromine/triphenylphosphine in anhydrous dichloromethane); this afforded the corresponding per-6-bromides 24–26 in 46–94% yields. Final nucleophilic substitutions by n-octadecylthiolate afforded the desired targets 7–9 in 39–80% yields (Fig. 7.14). All synthesized β-cyclodextrin derivatives were characterized by 1D and 2D NMR experiments as well as MALDI-mass spectrometry.

Fig. 7.14

Synthetic scheme of per-6-octadecylthio-2-O-alkylated β-cyclodextrin derivatives 7-9

Mesomorphic Properties

The mesomorphic properties of β-cyclodextrin derivatives 4–5 were first investigated using differential scanning microscopy to reveal the phase-transitions as well as their associated enthalpic changes. It was found that both compounds 4–5 did not display liquid crystallinity, since only a single phase-transition was observed upon heating, which was attributed to the crystalline-isotropic liquid transition. Thus, clearly, the possible π-π interactions of benzene units present in 5 were not enough to induce long-range ordering in solid states. Interestingly, the two amphiphilic compounds 8–9 with larger groups (allyl for 8 and benzyl for 9) at O2-positons also displayed a single phase transition, as observed by differential scanning calorimetry. This observation was further confirmed by cross-polarized optical microscopy as no birefringence was detected. Thus, both compounds 8 and 9 were found to be incapable of self-assembling into liquid crystalline mesophases, despite the presence of 7-hydroxyl groups. Probably, intermolecular H-bonding network is too weak to induce long-range orders. On the other hand, the two amphiphilic compounds 6 and 7 with smaller alkyl groups (methyl 6 and ethyl 7) at O2-positions displayed thermotropic liquid crystalline behavior, with the compound 6 being the most mesogenic. From differential scanning calorimetry, compound 6 revealed five endothermic phase transitions upon heating at 50, 60, 64.5, 68, and 110 °C, and four exothermic transitions upon cooling at 95, 56, 40.5 and 37.5 °C (Fig. 7.15). From polarized optical microscope, the heating phase transition observed at 110 °C was associated to the transition to the isotropic liquid phase. However, after cooling to 95 °C, compound 6 displayed fluidity and the characteristic fan-shaped smectic A pattern became increasingly bright and colorful upon further cooling while the material became highly viscous.

Fig. 7.15

DSC thermogram of compound 6 (Top) and its POM snapshots at 77.5 and 43.5 C (Bottom) “Reprinted with permission from (Ward et al. 2014). DSC differential scanning calorimetry, POM cross-polarized optical microscopy. Copyright 2014 Royal Chemical Society

On the other hand, compound 7 which had seven O2-ethyl groups - just one carbon longer than the O2-methyl groups in 6 and one carbon shorter than the O2-allyl group in 8, displayed only two broad endothermic transitions at 54 and 61 °C upon heating, three broad and unresolved exothermic transitions at 43.5, 49 and 51.5 °C during the cooling cycle from the differential scanning calorimetry thermogram (Fig. 7.16). The heating transition observed at 61 °C was determined to be the clearing point of the material into isotropic liquid by cross-polarized optical microscopy. Upon cooling, the characteristic fan-shaped texture of smectic A gradually appeared, but the domains formed were generally much smaller than those of compound 6, suggesting weakening ability for compound 7 to self-assemble.

Fig. 7.16

DSC thermogram of β-CD 7 (Top) POM picture at 57.6 and 36.8 C (Bottom) “Reprinted with permission from (Ward et al. 2014). DSC differential scanning calorimetry, POM cross-polarized optical microscopy. Copyright 2014 Royal Chemical Society

Powder X-ray analysis was carried out for compound 6 which confirmed the presence of long range order in the smectic phase. For example, a bilayer thickness of 40.7 Å was determined; this value is significantly smaller than the calculated length (62.2 Å) of head-to-head dimer, suggesting significant interdigitation of the hydrophobic chains in the highly ordered solid states. The presence of broad peaks in the wider angles region were also detected, which suggests the presence of short range orders within the layers at lower temperatures but no distinct phase could be identified. However, the short-range orders disappeared at higher temperatures, as those broad peaks vanished in the determined X-ray diffractograms.

The investigation by Ling and co-workers (Ward et al. 2014) provided great insights on the importance of H-bonding strength on the formation of liquid crystalline mesophases. As can be seen, the per-2-O-methyl-β-cyclodextrin 6 had only half number of secondary hydroxyl group compared to compound 3e, thus intermolecular H-bond network established by compound 6 would be expected to be weaker. This substantially lowered the mesophases temperature (50–110 °C for compound 6 vs 215–280 for 3e). The ability to form smectic mesophases quickly diminishes from compound 6 to 7 and was completely lost when the chains length attached to O2 reached 3 carbons or longer. A substantially narrower temperature range was observed for compound 7 (range: 54–61 °C) which reflects the transition.

Previously, through ab initio and semiempirical quantum calculation, (Avakyan et al. 2001) proposed models of two types of inter and intramolecular H-bonding networks at the secondary faces of β-cyclodextrin dimers (Fig. 7.17). In type I model, OH-2 groups of one β-cyclodextrin act as H-bond acceptor to the neighboring OH-3 within the same molecule, while the same OH-2 groups simultaneously acts as a hydrogen bond donor to OH-3’s of another cyclodextrin molecule. In another type II model, both OH-2’s and OH-3’s assume a reversed role within inter- and intramolecular H-bond networks. The computational analysis confirmed type I to be thermodynamically preferred as the torsion angle of OH-2 favors the formation of intermolecular H-bonding network. Based on this model, Ling and co-workers found that for both compound 6 and 7, their per-substitutions at the O2 forbids the formation of the stronger type I network; thus, they concluded that within the mesophases formed by compounds 6 and 7, type II network was established with OH-3 acting dynamically as H-bond donor through inter and intramolecular interactions within the bilayer. Such model can be effectively used to explain the difference on the clearing point temperatures between compounds 3d/3e which did not display any clearing point, instead, they slowly decomposed at temperatures above 280 °C, confirming the very strong inter- and intramolecular H-bond networks present in such systems. Conversely, for compounds 6/7: only weaker inter- and intramolecular H-bond networks could be established. This explains well their lower clearing points at 110 °C and 56 °C for β-cyclodextrin 6 and 7 respectively.

Fig. 7.17

Graphical representation of the two distinct H-bonding networks present in β-cyclodextrin liquid crystals

7.2.1.2 Dipole-Dipole Intermolecular Force Mediated Mesophase Formation Based on Oligoethylene Glycol Functionalized β-Cyclodextrin

For more than a decade, H-bond network was considered to be very important to generate cyclodextrin-based liquid crystals. This intermolecular force has been found to play a crucial role in most published designs of cyclodextrin-based thermotropic liquid crystals (Ling et al. 1993; Shaikh et al. 2007; Yang et al. 2013). Recently, Ling and co-workers (Champagne et al. 2016) reported the first β-cyclodextrin-based liquid crystals (Fig. 7.18, 27–29) relying on using dipole-dipole interactions as the primary intermolecular force to induce self-assembly. The novelty of their design can be appreciated by the absence of any polar hydroxyl groups, but the presence of 14 ω-acetoxy-oligoethylene glycol residues of different lengths (2–4 repeating ethoxy groups) at the secondary face of β-cyclodextrin that are rich with polar C-O bonds. At the primary face, they kept the flexible, apolar n-octadecylthio functional groups. Thus, this class of compounds does show amphiphilic properties, but in solid states, due to lack of H-bond donors, the molecules are unable to interact with each other via H-bond network, thus the dipole-dipole interactions between the numerous C-O bonds of the oligoethylene glycol groups would be expected to play the most fundamental role to induce long-range orders in solid states.

Fig. 7.18

Graphical representation of the stuctrure of cyclodextrin-based liquid crystalline materials 27–29 forming smectic mesophases

Compounds 27–29 were synthesized from the per-6-O-tert-butyldimethylsilyl-β-cyclodextrin 20, which was first peralkylated at all O2 and O3 positions with propargyl bromide using sodium hydride as base in anhydrous dimethylformamide. The obtained per-2,3-O-dipropargylated compound 30 was then subjected to a full O-desilylation under acidic conditions (HCl) in a methanol-dichloromethane mixture, to yield desired heptol 31. After a per-6-mesylation with mesyl chloride in a mixture of anhydrous pyridine and dichloromethane at 0 °C, a highly versatile intermediate 32 was obtained. The alkynic functionalities were subjected to copper(I)-mediated 1,3-dipolar cycloaddition with 3 different ω-acetoxyoligoethylene glycol azides 33–35 of different lengths to obtain the corresponding conjugates 36–38. The final step involved the nucleophilic substitution of all the 6-mesylates in compounds 36–38 by n-octadecylthiolate to afford the desired targets 27–29 (Fig. 7.19).

Fig. 7.19

Synthesis of CD-based liquid crystalline materials 27–29 containing polar ω-acetoxyoligoethylene glycol groups

Thermogravimetric analysis revealed that all compounds 27–29 have excellent thermal stability (up to 283 °C, ca. 5% mass loss). The mesogenic behavior of compounds 27–29 was studied by cross-polarized optical microscopy, differential calorimetry, and powdered X-ray diffractometry. Remarkably, all three derivatives showed strong liquid crystalline properties over a wide range of temperatures. For example, under cross-polarized optical microscopy, compounds 27–29 were observed to clear into isotropic liquid phase at 234.3, 194.8, and 157.7 °C respectively (Fig. 7.20). The compound with the shortest oligoethylene glycol chains 27 cleared at the highest temperature, which was unexpected. Upon slow cooling, all three compounds gradually entered into liquid crystalline phases initially forming small bâtonnet domains that gradually grew and fused into larger bâtonnets which eventually fused together and formed fan-shaped textures. The bâtonnets are commonly observed textures at the transition from the isotropic phase to fluid smectic mesophases. Compared to the mesophases formed via stronger H-bonding network as the intermolecular forces (3d-3d, 6–7), Champagne et al. reported much enhanced fluidity for mesophases formed by compounds 27–29.

Fig. 7.20

Cross-polarized optical microscopy (POM) images images of β-cyclodextrin 27–29 recorded at various temperatures, highlighting their behavior from isotropic transition (I) to room temperature (V)

Differential scanning calorimetry thermoanalysis revealed a transition at 54.8, 45.9 and 39.3 °C for compounds 27–29, respectively; they correspond to a relatively large enthalpy change (24.3 Jg⁻¹ for 27, 19.9 Jg⁻¹, for 28, and 23.3 Jg⁻¹ for 29); the authors attributed them to the liquid crystalline mesophases to crystalline solid transition for each compound. Thus, all three compounds 27–29 form mesophases over an extremely wide range (179.5 °C for 27, 148.9 °C for 28, and 118.4 °C 29), which is remarkable, making this class of compounds unique. On the other hand, differential scanning calorimetry also revealed very small enthalpic variations (< 2.5 Jg⁻¹) for all three compounds 27–29 ascribed to the liquid crystalline-isotropic liquid transitions (Fig. 7.21 ). These enthalpic changes are much smaller when compared to the values associated with previously reported systems that relied on H-bond network (3d-3e, 6–7). For instance, compound 6 has an enthalpy change of ~19–20 Jg⁻¹ corresponding to its isotropic liquid-smectic liquid crystal phase transition. The higher fluidity, lower clearing temperature, and better thermostability are attributed to the absence of stronger H-bonding network. All these also contributed to the improved liquid crystalline properties of compounds 27–29.

Fig. 7.21

Differential scanning calorimetry (DSC) thermograms recorded for β-cyclodextrin derivatives 27 (I) and 29 (II) as well as the enthalpies associated with the recorded transitions

Solid state Molecular Packing Properties

Champagne et al. reported the powder X-ray diffractograms of 27–29 at 20 °C and 50 °C below their respective clearing point. Sharp peaks were observed in the low angle region for all three compounds, corresponding to layer spacing of 55–60 Å, confirming the formation of bilayer structures for all three compounds. This suggested that all three compounds formed smectic liquid crystalline mesophases. On the other hand, broad peaks were also observed in the higher angle region at higher temperatures, which was attributed to a lack of high intra-layer orders. However, when the X-ray diffractograms of compounds 27 and 29 were recorded at room temperature, the peaks in the higher angle region became significantly sharper, which suggested higher positional order within the layers.

Figure 7.22 shows molecular models of packing patterns for compounds 27–29. All three compounds have a conical geometry with calculated length of the molecules varying between 43.6–51.4 Å. The X-ray diffraction data revealed a periodicity much shorter than twice the molecular length in each case, suggesting significant interdigitation in solid states for each compound. Based on the wedge-shaped geometry of each derivative, the authors believed the interdigitation occurs at the hydrophobic chain region (primary face).

Fig. 7.22

(a) Corey-Pauling-Koltun models displaying the inherited wedge-shaped geometry of compounds 27–29, with a length of 43.6, 47.7 and 51.4 Å respectively, in extended conformation. (b) Proposed model of smectic packing in solid states for all three compounds, with interdigitation at the hydrophobic chain regions

7.2.2 Thermotropic Liquid Crystals Based on Cyclodextrin Derivatives Containing Conventional Mesogenic Groups

Mesogens consist of a group of organic compounds that strongly induce liquid crystallinity. These are often rigid molecules such as cholesterol, biphenyl, triphenylene that adopt the shape such as rods, disks etc. When chemically modified with flexible chains, their derivatives usually exhibit mesogenic behavior. Although cyclodextrin molecules represent a class of relatively rigid scaffolds, their mesogenic properties appear to be quite weak. For example, all compounds 4, 5, 8, and 9 did not show any liquid crystalline properties, despite the incorportation of several long alphatic chains at the primary face of the molecules. However, several research groups have reported examples of cyclodextrin-based liquid crystals by incorporating commonly known mesogenic groups to a cyclodextrin scaffold, and the obtained compounds usually displayed mesophases other than smectic.

7.2.2.1 Amphiphilic Cyclodextrin Derivatives Containing Cholesterol Residues

Shaikh et al. (2007) reported a first example of amphiphilic β-cyclodextrin-based thermotropic liquid crystal in 2007 by covalently linking β-cyclodextrin to monocholesteryl succinate 39 (Fig. 7.23). The synthesis began with an esterification of cholesterol 40 with succinic anhydride in presence of pyridine; this afforded the corresponding cholesterol succinate 41 with a free carboxylic acid. The available carboxylic acid was then activated with thionyl chloride to obtain the corresponding succinyl chloride 42, which was subsequently used to esterify β-cyclodextrin in anhydrous dimethylformamide at approximately 70 °C for 72 h. The β-cyclodextrin derivative 39 was obtained, unfortunately as a mixture. The degrees of cholesteryl substitution were estimated to be ~2–3, and most substitutions probably occurred at the primary face of the β-cyclodextrin, due to the higher nucleophilicity of OH-6 groups.

Fig. 7.23

Synthesis of cholesterol appended β-cyclodextrin liquid crystal derivatives 39

The thermotropic mesomorphic behaviour of product mixture 39 was investigated by the authors using various techniques, including Fourier-transform infrared spectroscopy, NMR, differential scanning calorimetry, and cross-polarized optical microscopy. The mixture exhibited birefringence above 130 °C (first heating), and became isotropic at about 180 °C. The differential scanning calorimetry thermogram showed a transition at 120–125 °C associated to the glass-liquid transition. This was well compared to native β-cyclodextrin, which does not exhibit any liquid crystalline properties and was reported to be stable up to 299 °C without experiencing any significant mass loss (Song and Xu 2008; Song et al. 2008). The cross-polarized optical microscopy analysis revealed unclear textures which were not fully characterized. Nevertheless it was interesting to see the synthesized materials displayed birefringence, even with such a low degree of substitutions. Cholesterol is known to induce cholesteric mesophases, thus the liquid crystalline properties of compound 39 was clearly due to the incorporation of cholesterol residues to β-cyclodextrin, and this had significantly reduced the strength of both the inter- and intramolecular H-bonding network of the materials in solid states.

7.2.2.2 Amphiphilic Cyclodextrin Derivatives Containing 4-methoxybiphenyl Residues

Chen et al. (2010) reported another amphiphilic β-cyclodextrin derivative 43 (Fig. 7.24) that was modified with a hydrophobic tail derived from the propargyl 6-(4′-methoxybiphenyl-4-yloxy)hexanoate group 46 at all the primary positions. The efficient copper (I)-mediated 1,3-dipolar cycloaddition was used to complete the hydrophobic modification of β-cyclodextrin core via the per-6-azide intermediate 45 in dimethylformamide. Thus, in the final molecule 43, Chen et al. incorporated 7 copies of 4′-methoxybiphenyl group which is known to induce liquid crystallinity because of its rigidity and rode-like geometry. In solid states, the 4′-methoxybiphenyl groups can interact with each other via π-π interactions. The purity of the final compound 43 was verified by ¹H NMR spectroscopy, Fourier-transform infrared as well as MALDI-TOF mass spectrometry.

Fig. 7.24

Synthesis of cyclodextrin-biphenyl thermotropic liquid crystal 43 forming smectic mesophases

Thermogravimetric analysis revealed the amphiphilic compound was quite stable at high temperature, as only a loss of 5% mass was observed at 318.5 °C. Differential scanning calorimetry thermoanalysis showed several phase transitions. For example, during the second heating cycle, endothermic transitions at 130.1 °C, 188.7 °C and 217.2 °C were observed with the last one correlating to the clearing temperature to isotropic liquid. Using cross-polarized optical microscopy, the birefringent properties of compound 43 were investigated, which revealed very interesting patterns. For example, at 50 °C, fan-shaped textures were observed, which transition into conic focal patterns at 180 °C and subsequently into schlieren lines at 195 °C that persisted until the material completely cleared into isotropic phase at 230 °C. The ability to form various mesophases revealed the great self-assembly ability of compound 35. This also differentiates it from other amphiphilic cyclodextrin derivatives that show liquid crystallinity.

Wide angle X-ray diffractometry was used to analyze the mesophases formed by compound 43. At 30 °C, 3 peaks in the small-angle region were observed with q ratios of 1:2:3; this allowed the authors to assign the structure of formed mesophase to be lamellar. In the wide-angle region, 3 peaks were also observed with 1 very strong, 1 strong, and 1 weak. Based on the characteristic patterns, Chen et al. concluded that compound 43 formed highly ordered smectic E mesophase at low temperatures. At 160 °C, the material showed similar diffraction patterns at the low-angle region (virtually unchanged), suggesting that the layered smectic structure was maintained. However, peaks in the wide-angle region did become broader, suggesting a slow transition to smectic A mesophase (Koltzenburg et al. 1998). Upon increasing temperature further to 200 °C, wide angle X-ray diffractometry detected no peaks within the low angle region, while only a diffused halo appeared in the high-angle region, corresponding to a phase transition to nematic phase: losing the layered structures (Dong et al. 2004). The material eventually entered its isotropic liquid phase at ~230 °C. Figure 7.19 depicts the proposed self-assembled supramolecular packing model of compound 43. As can be seen, the strongest intermolecular force that dictates the molecules to self-assemble was the H-bonding network occurring at the secondary face of β-cyclodextrin, resulting in dimerization. Such network persists from room temperature to the high clearing point into isotropic liquid state thus is responsible for the formation of lamellar structures in solid states. The lamellar organization of molecules is further promoted by the 4′-methoxybiphenyl units which interact with one another via intermolecular π-π-interactions. Chen et al. proposed that 3 or 4 of the biphenyl mesogenic units were oriented in opposite directions with respect to the primary face of the β-cyclodextrin; this adds a second level of orders that are responsible for formation of smectic E mesophases. The π-π-interactions between the 4′-methoxybiphenyl units became significantly disrupted at higher temperatures (during the smectic A and nematic phases). The authors confirmed such mode of organization through molecular modelling. For example, the calculated d spacing between opposing 4′-methoxybiphenyl units at the primary face of β-cyclodextrin is 38.6 Å, which matches almost perfectly the determined d spacing of 38.4 Å by wide angle X-ray diffractometry at room temperature (Fig. 7.25).

Fig. 7.25

Suggested lamellar organization of compound 43 in the smectic E mesophases

7.2.2.3 Cyclodextrin Derivatives Containing a Triphenylene Mesogenic Group

In 2013, another β-cyclodextrin-based thermotropic liquid crystal was reported (Yang et al. 2013). The authors conjugated a mesogenic triphenylene group to a β-cyclodextrin scaffold (Fig. 7.26). Triphenylene derivatives represent one of the most widely studied discotic mesogens due to their potential applications in many areas including light-emitting diodes, organic photovoltaic cells, organic field-effect transistors, gas sensors, and photocopying machines (Zhang et al. 1992; Kumar 2004; Kato et al. 2006; Laschat et al. 2007; Sergeyev et al. 2007; Cammidge and Gopee 2009). The synthesis began with a monotosylation of β-cyclodextrin under basic conditions (aqueous NaOH) to obtain compound 49, followed by a conversion to monoazide 50 in a mixture of dimethylformamide and water, and subsequently, conjugation with triphenylene derivative 38 containing five flexible O-n-pentyl chains and one O-propargyl group via the copper (I) promoted 1,3-dipolar cycloaddition. The obtained amphiphilic triphenylene-β-cyclodextrin conjugate 52 was then investigated using cross-polarized optical microscopy, but unfortunately, no mesophase was identified. In fact, compound 52 slowly decomposes without transitioning into isotropic liquid. Compound 52 was subsequently esterified, with acetic anhydride or n-butanoic anhydride, to afford the corresponding non-amphiphilic conjugates 47 and 48 respectively.

Fig. 7.26

Synthetic scheme of triphenylated-β-cyclodextrin columnar liquid-crystalline materials

Interestingly, using cross-polarized optical microscopy, only the per-O-acetylated compound 47 was found to display mesogenic properties, with the characteristic fan-shaped textures associated to columnar mesophase observed (Prasad et al. 2003; Wan et al. 2003; Ba et al. 2003; Paraschiv et al. 2007). The more flexible compound 48 did not exhibit any birefringence upon heating, as a direct transition from solid state to isotropic phase was observed. For compound 47, Differential scanning calorimetry only revealed two transitions upon heating at 115.2 °C and 160.4 °C, which correspond to crystalline-columnar mesophase-isotropic liquid transitions.

X-ray powder diffraction pattern of cyclodextrin derivative 47 revealed characteristic patterns of a triphenylene-based columnar mesophase. Peaks at the low angle and high angle regions were observed, and corresponded to the diameter of the columnar triphenylene groups (16.8 Å), the average distance of the molten alkyl chains (4.9–3.7 Å) and the intracolumnar spacing (3.6 Å). Yang et al. concluded that the presence of the strong H-bonding network was an obstacle for the formation of cyclodextrin-based liquid crystals. This H-bond network was eliminated through esterification, thus providing the molecules with the ability to self-assemble via π-π-interactions through the triphenylene moieties. However, the roles of β-cyclodextrin played during mesophase formation appear to be less important (Fig. 7.27).

Fig. 7.27

The proposed columnar packing model of triphenylene-β-cyclodextrin conjugate 47

7.2.3 Polymeric Cyclodextrin-Based Thermotropic Liquid Crystals

Recently, liquid crystalline polymers have received considerable attention due to their potential use as biomedical materials, photoelectric materials, switches, smart and stimuli responsive materials (Verploegen et al. 2009; Kim et al. 2014; Wang et al. 2014; Gündüz 2015; Mamiya et al. 2015). Liquid crystal polymers containing cyclodextrin molecules are of particular interests because of their cavities which can be used for host guest interactions with different properties. There have been two types of cyclodextrin-based liquid crystalline polymers reported in the literature so far: the first is related to cyclodextrin-based star-shaped polymers and the second is related to cyclodextrin-based rotaxane polymers.

7.2.3.1 Cyclodextrin-Core Star-Shaped Thermotropic Liquid Crystals

In 2009, He and co-workers (He et al. 2009) reported the synthesis and characterization of an α-cyclodextrin-based star-shaped polymer via atom transfer radical polymerization. Owing to circular geometry and multivalent functionality (18–24 hydroxyl groups), cyclodextrin molecules possess great potential to be used as scaffold to generate star-shaped polymers (Ohno et al. 2001; Stenzel-Rosenbaum et al. 2001; Karaky et al. 2005). Materials of such kind could find applications as switchable windows, displays, color projectors, and other electric-optical systems (Doane et al. 1986; Lin et al. 1995; Bouteiller and Barny 1996; Petti et al. 2003; Serhatli and Kacar 2006). Azobenzene is the moiety that attracted the utmost interest due to its reversible photoisomerization (Han et al. 2006). To synthesize the desired copolymer, α-cyclodextrin was first esterified with 2-bromoisobutyryl bromide, to generate a star-shaped core (incomplete substitutions were recorded, average degree of substitution: 13) containing numerous radical initiating sites; which was subsequently polymerized with a previously synthesized methacrylate derivative containing a flexible hexyl chain terminated with a 4-methoxy-4-oxy-azobenzene mesogenic group. The radical polymerizations were mediated by CuBr/Spartein using four different ratios of monomer methacrylate vs α-cyclodextrin core. All synthesized polymers showed a polydispersity index of approximately 1.5.

The thermotropic liquid crystalline properties of the synthesized materials were investigated and they all displayed both smectic-nematic phase transitions. The observed temperatures associated with smectic to nematic as well as nematic to isotropic phase transitions increased with molecular weights. For instance, the polymer obtained from combining methacrylate: α-cyclodextrin core of 60:1 was observed to display characteristic schlieren nematic textures after being heated to isotropic liquid and subsequently cooled below 125 °C; further cooling to 80 °C yielded the representative smectic textures.

The photoresponsive behavior of the material was investigated in tetrahydrofuran by UV-Vis spectroscopy. After irradiation at 360 nm, the intensity of the π→π* transition band decreased, which contrasted with a noticeable increase of the n→π* transition. The complete isomerization of the azobenzene moieties was observed after irradiating the sample for 5 min. As expected, the reverse trans-cis isomerization happened thermally and /or photochemically in which the trans isomer being thermodynamically favored by approximately 48 kJ/mol (Corruccini and Gilbert 1939).

7.2.3.2 Polyrotaxane-Based Thermotropic Liquid Crystals

Polyrotaxanes consist of a class of supramolecular polymers that have non-covalently linked cyclic organic structures such as cyclodextrins or crown ethers, threaded on a linear polymer such as polyethylene glycol chains. The cyclic molecules are mechanically locked with the threading polymer by bulky caps placed at each end of linear polymer (Gibson et al. 1994). Since their synthesis was first reported by Harada et al. in 1992, polyrotaxanes have attracted a considerable interest from the research community (Harada et al. 1992). One of their most interesting properties is the ability of cyclic structures to rotate and slide over the linear polymer chain. This feature allowed the preparation of fascinating materials such as molecular tubes, obtained by cross-linking macrocycles onto a single thread (Harada et al. 1993). Polytotoxanes have also found various applications (Okumura and Ito 2001) in designing stimuli-responsive properties such as antiscratching, self-healing (Noda et al. 2014), pressure sensitive drug releasing systems (Katsuno et al. 2013). The advantages of designing liquid crystalline materials based on polyrotaxanes are the absence of covalent linkages, resulting in materials with great fluidity, a useful parameter in thermotropic liquid crystals.

In 2007, Ito et al. (Kidowaki et al. 2007) reported a very interesting polyrotaxane-based thermotropic liquid crystal based on α-cyclodextrin. In their design, they conjugated a derivative of hexanoyl chloride which was functionalized with a mesogenic 4′-cyanobiphenyl residue at the end of the chain, to a rotaxane, pre-formed by threading α-cyclodextrin onto polyethylene glycols. 1-Amdantanamine was used as the cap for the polyrotaxane due to its unusually high binding affinity to α-cyclodextrin (Cromwell et al. 1985; Eftink et al. 1989; Gelb and Schwartz 1989; Palepu and Reinsborough 1990; Kwak and Gomez 1996; Harries et al. 2005). The average molecular weight of the rotaxane was ~35,000 (~110 copies α-cyclodextrin per thread) which represented ~28% coverage of the polyethylene glycol axis. Figure 7.26 shows a schematic representation of the synthesized polyrotaxane polymer. Using ¹H NMR spectroscopy, it was estimated that about 42% of the hydroxyl groups of α-cyclodextrin reacted with the hexanoyl chloride derivative, which translates into approximately 7.6 cyanobiphenlyl units per α-cyclodextrin (Fig. 7.28).

Fig. 7.28

Schematic representation of 6-(4′-cyanobiphenyl-4-yloxy)hexanoyl-functionalized polyrotaxanes based on α-cyclodextrin. “(Kidowaki et al. 2007)”. Copyright 2007 American Chemical Society

Differential scanning calorimetry revealed one endothermic transition at 136 °C upon heating, and two exothermic transitions respectively at 70 and 129 °C upon cooling. The phase transition at 70 °C was attributed to a glass transition while the phase transition at 129 °C was attributed to the biphenyl mesogenic side chains.

Using cross-polarized optical microscopy, schlieren-like texture was observed at 100 °C, indicating the presence of a nematic mesophase (Fig. 7.29). The brightness of the texture gradually increases with decreasing temperature, and were preserved at room temperature which is indicative of a liquid crystalline glass state at ambient temperature. X-ray diffraction patterns measured at 25, 80 and 180 °C further confirmed the presence of a nematic mesophase at temperatures below 130 °C.

Fig. 7.29

Schlieren-like texture observed for 6-(4′-cyanobiphenyl-4-yloxy)hexanoyl-functionalized polyrotaxanes. “(Kidowaki et al. 2007)”. Copyright (2007) American Chemical Society

Following the work of Ito et al., Araki and co-workers (Araki et al. 2014) later reported another α-cyclodextrin-polyrotaxanes-based thermotropic liquid-crystal by simply grafting mPEG2000 dicarboxylic acid to similar polyrotaxne as above, using 1,1-carbonylbis-1H-imidazole as the coupling reagent to obtain polyrotaxane-mPEG2000 copolymer with an estimated 75 copies of mPEG2000 per chain. The authors describe the geometry of their polymer as “sliding graft copolymer” which has a ‘rope-curtain like’ structure (Fig. 7.28 ).

Cross-polarized optical microscopy confirmed the fluidity of the material at 65 °C and formation of Grandjean terrace texture, typically associated with the formation of smectic mesophases (Oh 1977; Oswald and Pieranski 2005). On the other hand, X-ray diffraction at ambient temperature revealed several peaks associated with crystalline PEG (Barnes and Ross 1936; Bortel et al. 1979). At temperatures above 65 °C, X-ray diffraction also confirmed the formation of smectic A mesophase with a layer distance of 14.1 nm, corresponding to the predicted contour length of mPEG2000 (13.18 nm). Thus, despite the absence of mesogenic groups, this material was capable of self-organize into smectic A mesophases. The authors attributed the properties of the materials to the one-directional free sliding and rotation of each mPEG2000 grafted α-cyclodextrin subunit on the polyethylene glycol axis (Fig. 7.30).

Fig. 7.30

Schematic representation of formed smectic A mesophases by α-cyclodextrin-based polyrotaxane grafted with mPEG2000 chains. The free sliding and rotation of each mPEG2000 grafted α-cyclodextrin subunit on the polyethylene glycol axis facilitates the self-organization of the mPEG2000 side chains into large organized domains

Additionally, Hu and co-workers (Hu et al. 2011) also prepared a series of α-cyclodextrin-polyrotaxane derivatives conjugated with mesogenic azobenzene moieties by varying the spacer lengths between azobenzene and α-cyclodextrin. Their experimental results suggested that azobenzene-functionalized polyrotoxanes failed to show liquid crystalline behavior with spacer length of 2 and 4 while the analogous polyrotaxanes with spacer length of 6 displayed columnar nematic mesophase. However, when the spacer length was increased to 11, additional high ordered structures were formed by the azobenzene mesogens. Figure 7.31 illustrates a model of molecular organization in solid states for the azobenzene-functionalized polyrotaxanes with a spacer length of 11 carbons (Azo-PR-11).

Fig. 7.31

Graphical representation of polyrotaxane Azo-PR-11, molecular arrangement allowing enhanced β-cyclodextrin mobility on the polyrotaxane glycol thread

More recently, Guo and co-workers (Guo et al. 2016) reported a new kind of α-cyclodextrin-polyrotaxanes by grafting 4-phenylazobenzoyl moieties directly to cyclodextrin scaffolds without spacer. The parent α-cyclodextrin-polyrotaxane was prepared by mixing vinyl-polyethylene glycol and α-cyclodextrin in aqueous solution and subsequently caped with thiolated β-cyclodextrin. The azobenzene mesogen was then added directly to the free hydroxyl groups of cyclodextrins. The introduction of azobenzene moieties reduces the strength of inter and intramolecular H-bonding networks thus, successfully destruct the channel-like crystalline structure of the parent α-cyclodextrin-polyrotaxane, to provide enhanced mobility/rotation for cyclodextrin subunits on the thread. The introduced mesogenic groups engage intermolecular interactions to induce the thermotropic liquid crystalline behavior of the material (Fig. 7.32).

Fig. 7.32

Synthetic scheme of azobenzene-functionalized columnar nematic liquid-crystalline polymeric materials.

Cross-polarized optical microscopy revealed schlieren-like textures when the material was heated above 180 °C. In comparison, the parent unmodified α-cyclodextrin-polyrotaxanes did not display liquid crystalline behavior at any temperature. Interestingly, this 4-phenylazobenzoyl-functionalized α-cyclodextrin-polyrotaxane also showed lyotropic liquid crystalline behaviour in dimethyl sulfoxide solution at concentration of 5–0.2 wt%. With the help of wide angle X-ray diffraction patterns, the columnar nematic mesophase of the material was confirmed.

7.3 Cyclodextrin-Based Lyotropic Liquid Crystals

As discussed earlier, amphiphilic cyclodextrin derivatives have excellent ability to self-assemble in solvents, forming different self-assembled systems including lyotropic liquid crystals. In this development, Gulik and co-workers (Gulik et al. 1998) investigated the lyotropic liquid crytstal properties of a class of amphiphilic cyclodextrins, esterified at all secondary hydroxyl groups with acyl chains of different lengths (β-cyclodextrin-Cn; n = 6, 8, 10, 12, and 14; α-cyclodextrin-C₁₄, and γ-cyclodextrin-C₁₄). Both X-ray scattering and freeze fracture electron microscopy were used in their experiments. The structural analysis of the obtained cyclodextrins revealed that aliphatic chains are stacked similarly to lipid systems and arrange themselves in 2-D hexagonal phases. β-cyclodextrin-C6, -C8, -C10, and -C12 and γ-cyclodextrin-C14 were optically birefringent, while β-cyclodextrin-C14 and α-cyclodextrin-C14 were optically isotropic. X-ray diffractions revealed seven sharp reflections for β-cyclodextrin-Cn (n = 6, 8, 10, and 12) with dimensions of 25.9, 30.8, 33.0 and 35.3 Å, respectively. Interestingly, the birefringent materials produced were found to organize into polar columns of 2-D hexagonal lattice. Such results contrasted with γ-cyclodextrin-C14 which only displayed broad reflections associated to 2-D hexagonal lattice with dimension of 37.6 Å. On the other hand, α-cyclodextrin-C14 and β-cyclodextrin-C14 exhibited sharp reflections corresponding to body-centered cubic lattice of optically isotropic materials with dimension of 42.6 Å and 43 Å, respectively. The 2-D hexagonal phase of β-cyclodextrin-Cn (n = 6, 8, 10, and 12) and cubic lattice of α-cyclodextrin-C14 and β-cyclodextrin-C14 were further supported by freeze fracture micrographs (Fig. 7.33A–D). Compounds β-cyclodextrin-Cn (n = 6, 8, and 10) in hexagonal phases and α-cyclodextrin-C14 and β-cyclodextrin-C14 in cubic phases showed ordered and organized domains, respectively while less ordered domains were observed for β-cyclodextrin-C12. The polar columns of hexagonal phase comprised of stacked cyclodextrin units in which polar heads were pointed toward the interior of the self-assembled structure, while paraffinic units were projected toward the exterior (Fig. 7.33E). The respective cubic lattice of α-cyclodextrin-C14 and β-cyclodextrin-C14 consists of 12 molecules per unit cell. It was proposed that the cubic lattice comprised of either polar or paraffinic globules at the center and edges of the cell (Fig. 7.33F, G). The polar globules were comprised of six molecules of α-cyclodextrin-C14 or β-cyclodextrin-C14 (Fig. 7.33F) while paraffinic globules consist of dimers of α-cyclodextrin-C14 or β-cyclodextrin-C14 connected by their primary hydroxyl groups (Fig. 7.33G). The combined analysis of X-ray scattering, freeze fracture electron microscopy, and electron density distribution confirmed the paraffinic globules arrange themselves in the cubic lattice (Fig. 7.33G). The orientation of dimers, while occupying the middle of each edge, was parallel to axis of cubic cell and orthogonal to adjacent dimer. The formation of cubic lattice for such amphiphilic cyclodextrins was found to be unusual and was rationalized by the large surface area of the aliphatic chains.

Fig. 7.33

Freeze fracture electron micrographs of (A) β-cyclodextrin-C6, (B) β-cyclodextrin-C8, (C) β-cyclodextrin-C10, (D) β-cyclodextrin-C14 (Scale bar = 200 nm). (E) Two possible associations of 2D hexagonal structure models with polar columns of stacked cyclodextrin units. (F, G) The possible cubic structure models of α-cyclodextrin-C14 or β-cyclodextrin-C14 containing either polar (F) or paraffinic globules (G) at the vertex (in gray color). The paraffinic chains are omitted for clarity. (A–G) are adapted with permission from (Gulik et al. 1998). Copyright (1998) American Chemical Society

Cyclodextrins are well known to bind to various types of surfactants by inclusion of their hydrophobic tails into cyclodextrin’s cavity. Surfactants are widely used in daily practical applications including cleaning, emulsifying, detergents, paints, biocides, and insecticides (Rosen and Kunjappu 2012). Upon interactions with cyclodextrins, significant changes occurred in inherent properties and structural dynamics of surfactants. For instance, sodium dodecyl sulfate (SDS), a common surfactant abundantly used in cleaning, cosmetics, and hygiene products, exhibited different self-assembly behavior in the presence of β-cyclodextrin. Sodium dodecyl sulfate forms highly stable water soluble inclusion complexes with two β-cyclodextrin molecules (sodium dodecyl sulfate@2β-cyclodextrin) in 1:1 and 1:2 stoichiometry (Dorrego et al. 2000; Jiang et al. 2011). Generally, sodium dodecyl sulfate@2β-cyclodextrin complexes disfavor self-assembly in aqueous medium due to their hydrophilic outer surface (Saenger and Müller-Fahrnow 1988). However, self-assembled aggregates such as vesicular and lamellar mesophases were observed for sodium dodecyl sulfate@2β-cyclodextrin complex in aqueous solution. To gain deeper insight into such aggregation behavior, the concentration, H-bonds, and electrostatic interactions of the cyclodextrin/sodium dodecyl sulfate complex were investigated. It was observed that by changing the mass concentration of sodium dodecyl sulfate@2β-cyclodextrin complexes, three types of aggregates were formed, including: region I (50–25 wt%), region II (25–6 wt%) and region III (6–4 wt%) (Jiang et al. 2011). In mass concentration range of 50–25 wt%, semi-transparent self-assembled lamellar structures were identified, exhibiting static birefringence observed under cross-polarized optical microscopy, a suggestive of an anisotropic phase (Fig. 7.34A). The lamellar lattice was further confirmed by freeze-fracture transmission electron microscopic and X-ray scattering profiles. Images of uniform parallel lines were obtained from the vitrified sample which showed similar pattern to typical lamellar structures (Fig. 7.34B, C ). Further, small and wide angle X-ray scattering evaluations confirmed channel type crystalline bilayers associated in head to head pattern stabilized by strong H-bonding networks (Fig. 7.34F). Lamellar liquid-crystalline mesophases appeared in one direction while in-plane solid-crystalline orders appeared in other two directions. Such observations are characteristic features of transition phase between liquid crystal and solid.

Fig. 7.34

(A) NMR sample photographs of 30 wt% sodium dodecyl sulfate@2β-cyclodextrin without (left) and with (right) crossed polarizer. (B) and (C) freeze-fracture transmission electron micrographs of 30 wt% SDS@2β-cylodextrin complex. (D–I) Graphical illustration of sodium dodecyl sulfate@2β- cyclodextrin self-assembly: (D) Sodium dodecyl sulfateand β-cyclodextrin monomers, (E) sodium dodecyl sulfate@2β-cyclodextrin complex, (F) Bilayer membrane of sodium dodecyl sulfate@2β- cyclodextrin channels structure. (G–I) Transition of lamellae to microtubes and vesicles. (J) Structure of sodium dodecyl sulphate (SDS). (A–I) are adapted with permission from “(Jiang et al. 2011)”. Copyright 2011 Royal Society of Chemistry

Upon decreasing the mass concentration to 25–6 wt% of region II, large aggregates corresponding to microtubular structures were observed (Jiang et al. 2010a). Generally, tubular assembly is governed by non-directional hydrophobic interactions resulting in less-ordered soft aggregates. However, microtubes formed by the nonamphiphilic self-assembly of sodium dodecyl sulfate@2β-cyclodextrin with mass concentration of 25–6 wt% was driven by directional and ordered H-bonds instead of hydrophobic interactions. The formed microtubes appeared rigid, monodispersed and highly persistent in molecular dimensions owing to strong H-bond interactions. The microtubes were analyzed by confocal laser scanning microscopy using nile red as fluorescent dye that exhibits partial inclusion in the cavity of β- cyclodextrin (Hazra et al. 2004) (Fig. 7.35A, D). The fluorescent walls with non-fluorescent center of microtubes demonstrate the uniform pattern of hollow tubular structures (Fig. 7.35A, D). Similar pattern was observed in the absence of nile red by confocal laser scanning microscopy and transmission electron microscopy (Fig. 7.35B, C). The mean diameter and length of microtubes were 1.1 μm and 40 μm, respectively with wall separation of 0.7 μM. Microtubes appeared quite inflexible as they preferred to be straight rather than bending (Fig. 7.35E). The multilamellar structure of microtubes displayed unique “annular ring” formation, when resolved by freeze-fracture transmission electron microscopy using vitrified sample of sodium dodecyl sulfate@2β-cyclodextrin. Figure 7.35F, H–K illustrates the appearance of annular ring changed to circles, ellipses, elongated ellipses and parallel lines upon changing the angle from 0 to 90° between radical plane and fractured surface. Further analysis by atomic-force microscopy and wide-angle X-ray scattering revealed bilayer architecture of microtubes. The nonamphiphilic self-assembly of sodium dodecyl sulfate@2β-cyclodextrin complex to microtubules was attributed to the H-bonding and electrostatic interactions between each complex. Such results were quite interesting since recently, tubular assembled architectures have gained considerable attention in different applications including sensing, synthesis, and drug delivery (Shimizu et al. 2005; Lee et al. 2009).

Fig. 7.35

(A, D) Confocal laser scanning microscopy images of 10 wt% sodium dodecyl sulfate@2β-cyclodextrin solution microtubes, (B) Differential interference contrast microscopy image, (C) Transmission electron microscopy image, (E) Diameter distribution of the microtubes, (F–K) Annular ring structure of the microtubes. (F) Cross sections view of microtube upon changing angle (θ) from 0 to 90° between radical plane and fractured surface, (G) Small-angle X-ray scattering profile of the microtubes, and (H–K) freeze-fracture transmission electron micrography images of the microtubes at different angle (θ) 0° (H), 30° (I), 70° (J), and 90° (K). (A–K) are adapted with permission from (Jiang et al. 2010a). Copyright 2010 Royal Society of Chemistry. (L and M) are adapted with permission from (Jiang et al. 2010b) and (Jiang et al. 2011). Copyright 2011 Royal Society of Chemistry.

Structural transformations were also observed upon diluting the mass concentration of sodium dodecyl sulfate@2β-cyclodextrin (6–4%) that led to transition of microtubular to vesicular phases containing unilamellar and bilamellar hollow vesicles with concave/ convex surfaces. Absence of diffraction pattern in small-angle X-ray scattering indicated the formation of unilamellar and bilamellar vesicles instead of multilamellar vesicles. Despite concentration dependency, the recurrent feature of lamellar, microtubular, and vesicle mesophases was the presence of bilayer membrane structures. At the intermediate margins of region I/II and region II/III, concurrence of lamella-microtube for 20 wt% and microtube-vesicle for 7 wt%, respectively were observed using confocal laser scanning microscopy images of entrapped nile red (Fig. 7.35L, M). Figure 7.35L illustrates non-fluorescent center corresponding to hollow microtubes with fluorescent walls of parallel lines as lamellar pattern. Similarly, spherical vesicles were found in the matrix of microtubes validating the cohabitation of lamellae, microtubes and vesicles (Fig. 7.35M). Such nonamphiphilic self-assembly driven by H-bonds and electrostatic interactions instead of hydrophobic interactions promoted the development of new designs to explore self-assembly behavior of cyclodextrin-based liquid crystalline systems.

The lyotropic liquid crystal properties of polyelectrolyte such as deoxyribonucleic acid (DNA) in the biological system depends upon its dispersion in lipids and interaction with counter ions (Dias and Lindman 2008). To this account, the aggregation of polyelectrolytes (DNA) and amphiphilic counter ions dodecyltrimethylammonium was investigated in the absence as well as in the presence of β-cylclodextrin and (2-hydroxypropyl)-β-cyclodextrin (Bilalov et al. 2012). In aqueous medium, DNA and dodecyltrimethylammonium essentially form self-assembled water-insoluble micelles and consequently change the liquid crystal phases of DNA. However, the presence of β-cyclodextrin or (2-hydroxypropyl)-β-cyclodextrin, as dispersion agents, redefines the liquid crystalline ordering of DNA by forming inclusion complexes with dodecyltrimethylammonium. The resulted amphiphiles are characterized by a greater degree of dispersion and increased solubility in water. With molar ratio R < 1 (R = [dodecyltrimethylammonium]/[cyclodextrin]) and increased dodecyltrimethylammonium-DNA concentration, 2D hexagonal liquid crystalline phases were observed (Fig. 7.36A, left). Upon further increasing the R > 1.5–2 and dodecyltrimethylammonium-DNA concentration, anisotropic tetragonal liquid crystal lattice possessing square packing was obtained (Fig. 7.36A, right). Interestingly, both 2D-tetragonal and 2D-hexagonal phases displayed parallel ordering of DNA duplexes.

Fig. 7.36

(A) Pictorial representation of hexagonal (left) and tetragonal (right) phases of the microstructures of dodecyltrimethylammonium-DNA-(2-Hydroxypropyl)-β-cyclodextrin, respectively. (B) Structure of dodecyltrimethylammonium bromide. (A) is adapted with permission from (Bilalov et al. 2012). Copyright 2012 Royal Society of Chemistry

The rigidity of polyelectrolyte dictates its phase behavior in aqueous medium, hence lyotropic liquid crystal properties. To validate the rigidity effect, a flexible electrolyte, polyacrylate was investigated and compared with DNA, which is relatively rigid (Carlstedt et al. 2012). An isotropic phase was observed in dodecyltrimethylammonium– polyacrylate with molar ratio R = 1 which was similar to dodecyltrimethylammonium–DNA system. With 20 weight percent of (2-hydroxypropyl)-β-cyclodextrin and R ≈ 2, dodecyltrimethylammonium–polyacrylate demonstrated optically isotropic and viscous cubic phase which was further validated by singlet in ²H-NMR spectra. Under similar composition of 20 wt %, hexagonal phase was also observable as optically anisotropic, and viscous with quadrupolar splitting pattern in ²H-NMR spectra. The cubic phase order of dodecyltrimethylammonium–polyacrylate system, and hexagonal and tetragonal phases of dodecyltrimethylammonium–DNA system were attributed to flexible nature of polyacrylate and stiffness of DNA, respectively while keeping the β-cyclodextrin and (2-hydroxypropyl)-β-cyclodextrin as the dispersion agents.

7.4 Applications of Cyclodextrin Based Liquid Crystals

7.4.1 Biosensing Based Inclusion and Cholesterol Detection

Over the years, liquid crystals have been used in numerous applications owing to their optical and dielectric anisotropic properties. These include liquid crystal displays, (Hee Lee et al. 2012; Bremer et al. 2013) technical (Goossens et al. 2016) and biological areas (Brake et al. 2003a; Mushenheim et al. 2014). Exploring the liquid crystal behavior at the interface of immiscible phases gave valuable insight on the self-assembled interactions of biomolecules such as proteins (Brake and Abbott 2002) and lipids (Hartono et al. 2008), as well as synthetic molecules including polymers (Brake et al. 2003b) and surfactants (Bai and Abbott 2011).

At the interface, the specific orientational order of liquid crystals changes into different order in presence of interfacial events. These transitions have been successfully applied as imaging tool for the investigating the biomolecular interactions at the cellular level (Park and Abbott 2008; Bi et al. 2009; Lowe and Abbott 2012). Zuo et al. (2014) used this strategy to investigate the host-guest interactions between β-cyclodextrin and sodium dodecylsulfate as well as methylene blue by employing a known mesogen, 4-cyano-4′-pentylbiphenyl (5CB), as nematic liquid crystals analyzed by cross-polarized optical microscopy. At aqueous interface, 4-cyano-4′-pentylbiphenyl self-assemble into nematic liquid crystals with bright images indicating their planer orientations (Fig. 7.37A). With addition of sodium dodecylsulfate, its hydrophobic tail was observed to interact with 4-cyano-4′-pentylbiphenyl that changed their orientations from planer to homeotropic, resulting in dark images of liquid crystals (Fig. 7.37A, B). Further, with the introduction of β-cyclodextrin, the sodium dodecylsulfate molecules showed better inclusion binding with β-cyclodextrin cavity leaving 4-cyano-4′-pentylbiphenyl to reorients themselves from homeotropic to planer order (Fig. 7.37A, C). This resulted into the reappearance of bright images (Fig. 7.37C). No significant change in optical appearance of 4-cyano-4′-pentylbiphenyl was observed upon addition of β-cyclodextrin in the absence of sodium dodecylsulfate except minor color change attributed to weaker 4-cyano-4′-pentylbiphenyl and β-cyclodextrin interactions. To validate the host-guest inclusion interactions, they employed methylene blue that exhibit stronger binding to β-cyclodextrin than sodium dodecylsulfate. Upon exposure of methylene blue to the interfacial solution of 4-cyano-4′-pentylbiphenyl +β-cyclodextrin+sodium dodecylsulfate on the copper grid, the dark images corresponding to homeotropic order reappeared after 30 mins. This is due to the greater binding affinity of methylene blue for the β-cyclodextrin cavity, resulting in the expulsion sodium dodecylsulfate molecules which interact with 4-cyano-4′-pentylbiphenyl again to form dark images.

Fig. 7.37

(A) Graphical illustration of host–guest complexation between β-cyclodextrin and sodium dodecylsulfate (or methylene blue) using a 4-cyano-4′-pentylbiphenyl LC sensor. (B-F) Cross-polarized images of copper grid containing 4-cyano-4′-pentylbiphenyl upon addition of various concentrations of sodium dodecylsulfate (mM): (B) 0, (C) 0.1, (D) 0.25, (E) 1.0, (F) 2.5. (G-L) Cross-polarized images of copper grid containing 5CB-SDS after addition of various concentrations of β-cyclodextrin (mM): (G) 0, (H) 0.1, (I) 0.25, (J) 0.8, (K) 1.0, (L) 2.5, concentration of sodium dodecylsulfate used = 0.25 mM. (M and N) Structure of 4-cyano-4′pentylbiphenyl (5CB) and methylene blue (A-L) are adapted with permission from (Zuo et al. 2014). Copyright 2013 Royal Society of Chemistry

The LC behavior of ternary complex 4-cyano-4′-pentylbiphenyl + β-cyclodextrin+sodium dodecylsulfatein the presence of methylene blue and dopamine was further investigated by quantum mechanical calculations using Gaussian 09 program package (Liu et al. 2016). PM3 semi-empirical method was used to simulate inclusion complexes of 4-cyano-4′-pentylbiphenyl, β-cyclodextrin, sodium dodecylsulfate, methylene blue, and dopamine which were again re-augmented at DFT B3LYP/6-31G(d) level. The theoretical analysis revealed that sodium dodecylsulfate formed strong inclusion complex with β-cyclodextrin at the interface of 4-cyano-4′-pentylbiphenyl/aqueous surface which resulted in the planer reorientation of liquid crystals. The addition of methylene blue excludes sodium dodecylsulfate from the cyclodextrin cavity to allow the formation of a stronger β-cyclodextrin-methylene blue complex. The simulated energy and complexation profile corroborated 1:2 (methylene blue:2β-cyclodextrin) complex formation through the wider secondary face of cyclodextrin which was more stabilized than sodium dodecylsulfate complex. In addition, it was observed that inclusion complex of dopamine+β-cyclodextrin was less stable than sodium dodecylsulfate+β-cyclodextrin or methylene blue+β-cyclodextrin, therefore no significant change in 4-cyano-4′-pentylbipheyl liquid crystal orientation was found upon addition of dopamine. The theoretical results were in compliance with experimental results observed by Zuo et al.

The inclusion interactions were further extended to examine the specific binding of guest molecule with appropriate host molecule using 4-cyano-4′-pentylbipheyl as liquid crystal imaging tool (Liao et al. 2015). α-cyclodextrin and β-cyclodextrin inherit different cavity sizes, thereby exhibiting different binding affinity for guest molecules. To validate this, they used cetyltrimethyl ammonium bromide as surfactant which exhibits different binding abilities toward α-cyclodextrin and β-cyclodextrin. The orientational order and optical appearance of 4-cyano-4′-pentylbiphenyl in the presence of cetyltrimethyl ammonium bromide was similar to sodium dodecylsulfate pattern. In the presence of cetyltrimethyl ammonium bromide, the planer orientation and bright images of copper grid coated with 4-cyano-4′-pentylbiphenyl changed to homeotropic order and its characteristic dark images. The reverse effect, regeneration of bright images and planer order, was observed upon exposure of 4-cyano-4′-pentylbiphenyl + cetyltrimethyl ammonium bromide films to α-cyclodextrin and β-cyclodextrin solutions. Interestingly, the rate of that transition was much faster for α-cyclodextrin than β-cyclodextrin. It was observed that, at the same concentration and time interval, the cetyltrimethyl ammonium bromide exhibited stronger affinity towards α-cyclodextrin and β-cyclodextrin as visualized by cross-polarized optical microscopy images, surface tension analysis and isothermal titration curve.

For the practical utility of this approach, competitive host-guest interactions at the liquid crystal-aqueous phases have been exploited for the detection of cholesterol and cholic acid. Cholesterol is a valuable component of cell membrane (Ikonen 2008) involved substantially in the biosynthesis of vitamin D and bile acids (Ram et al. 2001a). The high cholesterol level in the blood is implicated in cardiovascular and other diseases by plaque formation in the arteries. Thus, cholesterol detection by simple and effective method is always desirable despite currently available methods including electrochemical, (Dey and Raj 2010) enzyme-based biosensors, (Devadoss and Burgess 2002) and fluorescence spectroscopy (Mondal and Jana 2012). Park et al. developed a cholesterol biosensor by utilizing the sodium dodecyl sulfate/β-cyclodextrin complex on the interface of liquid crystal and aqueous medium (Munir and Park 2015). At the interface between aqueous medium and nematic liquid crystal, the small perturbation can make diverse changes in the orientation of nematic liquid crystal. Such behavior was utilized for cholesterol detection. Sodium dodecyl sulfate forms inclusion complex with β-cyclodextrin owing to host guest interactions (vide supra, Fig. 7.37A). The exposure of cholesterol at the interface between aqueous solution and nematic liquid crystal excludes the sodium dodecyl sulfate from sodium dodecyl sulfate/β-cyclodextrin complex due to stronger inclusion of cholesterol into β-cyclodextrin cavity. The excluded sodium dodecyl sulfate gets adsorbed at the interface, thereby changed the orientation of 4-cyano-4′-pentylbiphenyl as demonstrated by cross-polarized optical microscopy. The inclusion concentration of sodium dodecyl sulfate (340 μM) in sodium dodecyl sulfate/β-cyclodextrin complex was carefully analyzed using pH and high-performance liquid chromatography studies. The polarized optical microscope images of 4-cyano-4′-pentylbiphenyl anchored transmission electron microscopy grid cells showed in-plane birefringence illustrating their planer orientation at the interface. Similar planer orientations and bright coloring of cross-polarized optical microscope images were observed in the absence of cholesterol. The addition of cholesterol solution of varying concentrations changed the orientation of 4′-pentylbiphenyl from planer to homeotropic with appearance of dark patches attributed to exclusion of sodium dodecyl sulfate from sodium dodecyl sulfate/β-cyclodextrin complex. The calculated detection limit of cholesterol using this method was 3 μM which is biological relevant detection concentration. The insensitive liquid crystal behavior of 4-cyano-4′-pentylbiphenyl to common interfering analytes present in blood including sodium chloride, hemoglobin, ascorbic acid, and glucose validated the practical utility of this method.

The liquid crystal-aqueous interface self-assembled system was also used to detect cholic acid, a primary component (31%) of bile acids excreted by liver (Hofmann and Hagey 2008). The abnormal production of cholic acid directly correlates with the progress of liver disease (Rani et al. 2004). The concentration analysis of cholic acid in serum and urine provides valuable diagnosis of liver disease and associated treatment (Jorquera et al. 2005; Griffiths and Sjövall 2010). Fang et al. used β-cyclodextrin-C₁₄TAB (tetradecyl trimethylammonium bromide) complex appended 4-cyano-4′-pentylbiphenyl droplets for the facile detection of cholic acid (Fig. 7.38) (Deng et al. 2015). C₁₄TAB formed 1:1 complex with β-cyclodextrin in aqueous system with hydrophilic head and hydrophobic tail oriented toward secondary and primary faces, respectively (Valente and Söderman 2014). The primary face of β-cyclodextrin-C₁₄TAB complex partially protrudes hydrophobic tail (about 13 Å) which procures this complex a supramolecular surfactant behavior, allowing interactions with 4-cyano-4′-pentylbiphenyl liquid crystals. Cross-polarized optical images and positive zeta potential (+17.6 mV) of β-cyclodextrin-C₁₄TAB-appended-4-cyano-4′-pentylbiphenyl films illustrated the formation of radial configuration in which primary and secondary faces of β-cyclodextrin were oriented toward 4-cyano-4′-pentylbiphenyl and water phases, respectively. The addition of cholic acid changed the radial configuration of β-cyclodextrin-C₁₄TAB-appended-4-cyano-4′-pentylbiphenyl films to bipolar configuration (Fig. 7.38B, C) attributed to the inclusion of cholic acid into cavity of β-cyclodextrin through its primary face and consequently exclusion of C₁₄TAB. This was validated by observing decrease in surface tensions of 20 μM CA solution (52.6 mN m⁻¹ for) compared to 1.6 mM solution of β-cyclodextrin-C₁₄TAB (54.8 mN m⁻¹) suggesting 27.5% displacement of C₁₄TAB. The complexation of cholic acid with β-cyclodextrin-C₁₄TAB-appended-4-cyano-4′-pentylbiphenyl films was further verified by their bipolar fluorescent images measured by confocal microscope using cholyl-lysyl-fluorescein, a fluorescence derivative of cholic acid (Fig. 7.38D, E). The detection limit of the cholic acid was found to be 20 μM using liquid crystal imaging method. Furthermore, cholic acid was detected (detection limit = 60 μM) in synthetic urine sample (3.16 mM urea, 42.6 μM MgSO₄, 90.1 μM CaCl₂, and 1.36 mM NaCl) in the presence of interfering uric acid and urea, validating the practical utility of this method. Similar liquid crystalline behavior of 4-cyano-4′-pentylbiphenyl was observed upon interaction with (2-hydroxylpropyl)-β-cyclodextrin-C₁₆TAB complex highlighting the uniformity of detection method.

Fig. 7.38

(A) Pictorial representation of cholic acid-induced transition of 4-cyano-4′-pentylbiphenyl-β-cyclodextrin-C₁₄TAB(5CB-β-CD-C₁₄TAB) droplets from radial-to-bipolar configuration host–guest recognition. (B, C) Polarized optical microscope images of 4-cyano-4′-pentylbiphenyl-β-cyclodextrin-C₁₄TAB droplets before (B) and after (C) addition of 20 mM cholic acid at pH 7.4. (D, E) Polarized (D) and fluorescence (E) images of 4-cyano-4′-pentylbiphenyl-β-cyclodextrin-C₁₄TAB droplets after addition of cholyl-lysyl-fluorescein, a fluorescent cholic acid. (F) Structure of cholic acid and tetradecyltrimethylammonium bromide. (A–E) are adapted with permission from (Deng et al. 2015). Copyright 2015 Royal Society of Chemistry

7.4.2 CD Capped Nanoparticle and Liquid Crystal Displays

From last few decades, utilization of liquid crystal displays (LCD) and their electro-optic properties have flourished significantly in the electronic and communication industries. Despite their huge utility in revolutionizing modern technology, liquid crystal displays have been associated with slow electro-optical response. Various modifications have been done by doping liquid crystals with semiconductor nanoparticles (Du and Toshima 2007), carbon nanotubes (Chen and Lee 2006), metal nanoparticles (Shiraishi et al. 2002) and fullerene (Suzuki et al. 2001) to enhance response time and contrast, and lowering the driving voltage of liquid crystal displays. Cyclodextrin-capped SiO₂ nanoparticles (Cyclodextrin = α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin and poly-γ-cyclodextrin) have also been utilized for doping liquid crystals of 4-cyano-4′-pentylbiphenyl to enhance their response time. (Shiraishi et al. 2012). The dispersion of cyclodextrin-SiO₂ into the liquid crystals of 4-cyano-4′-pentylbiphenyl resulted into twisted nematic liquid crystal (TN-LCD) with comparative faster response time than pure 4-cyano-4′-pentylbiphenyl. The capped cyclodextrin-SiO₂ formed homogenous nanoparticles with average diameter of 9.4, 8.4, 10.6, and 6.4 nm for α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin and poly-γ-cyclodextrin, respectively corresponding to their protecting abilities (β-cyclodextrin > α-cyclodextrin > γ-cyclodextrin) (Komiyama and Hirai 1983). Doping of cyclodextrin-SiO₂ with 4-cyano-4′-pentylbiphenyl liquid crystals resulted in formation of twisted nematic liquid crystal with similar phase transition temperature (4-cyano-4′-pentylbiphenyl = 34.2 °C, α-cyclodextrin = 34.2 °C, β-cyclodextrin = 34.1 °C, and γ-cyclodextrin = 34.1 °C). The response time (τ_on: rise time of 90% -10% transmittance, and τ_off: fall time of 10%–90% transmittance) of twisted nematic liquid crystal of cyclodextrin-SiO₂ appended 4-cyano-4′-pentylbiphenyl were obtained by measuring the transmission of liquid crystals. Faster response time was observed for twisted nematic liquid crystal of cyclodextrin-SiO₂ + 4-cyano-4′-pentylbiphenyl (76.7, 71.5, and 90.7 msec for α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin respectively) compared to 96.2 msec of 4-cyano-4′-pentylbiphenyl alone attributed to capping, protection and solubilizing properties of cyclodextrin. Comparatively, β-cyclodextrin-SiO₂ + 4-cyano-4′-pentylbiphenyl liquid crystals showed faster response time over α-cyclodextrin, and γ-cyclodextrin due to better inclusion of 4-cyano-4′-pentylbiphenyl in β-cyclodextrin cavity. To visualize the practical utility of doped system, a liquid crystal device was developed using M03 (a commonly used practical liquid crystal in display industries) as host liquid crystal and poly-γ-cyclodextrin as stabilizer owing to its higher stability for longer time and better fall time. An enhanced response time of poly-γ-cyclodextrin-SiO₂ doped M03 liquid crystal display was observed validating its industrial application.

Further experiments were performed to investigate the doping effect of different metal nanoparticles such as barium titanate (BaTiO₃) (Shiraishi et al. 2015) and ZrO₂/Au (Shiraishi et al. 2016) capped with cyclodextrin on liquid crystals performance. Barium titanate exhibits high dielectric constant and ferroelectric properties, explaining its numerous applications such as electro-optical displays, and thermistors. Doping of nematic liquid crystals with BaTiO₃ were found to have strong electromechanical polarization fluctuations (Basu 2014) and pretransitional effects on the isotropic to nematic phase transitions (Čopič et al. 2007). To increase the compatibility and response time of liquid crystals, barium titanate was capped with γ-cyclodextrin and mixed with liquid crystals of 4-cyano-4′-pentylbiphenyl. Particles of γ-cyclodextrin appended barium titanate (2.1 nm diameter) prepared using microwave/ ultra-sonication showed better response time compared to solvothermal method (2.3 nm, 2.7 nm and 3.9 nm, at 240 °C, 270 °C and 300 °C, respectively) due to their higher dispersion with liquid crystals of 4-cyano-4′-pentylbiphenyl. Faster response of γ-cyclodextrin- BaTiO₃ doped 4-cyano-4′-pentylbiphenyl with τ _on = 58.55 msec and τ _off = 14.49 msec was found compared to pure 4-cyano-4′-pentylbiphenyl with τ _on = 60.57 msec and τ _off = 15.45 msec. The field sequential-color (FSC) specific liquid crystal NTN01 was doped with γ-cyclodextrin- BaTiO₃ nanoparticles and transmission was recorded. Response time of 3.99% was enhanced for NTN01 at 25 °C in the presence of γ-cyclodextrin-BaTiO₃ nanoparticles (τ _on = 10.43 msec and τ _off = 4.86 msec; τ _total = 15.29 msec) compared to homologous system in absence of γ-cyclodextrin (τ _on = 9.82 msec and τ _off = 4.86 msec; τ _total = 14.68 msec). On decreasing the temperature to 0 °C, 7.44% faster response time was observed. These results illustrated that doping liquid crystals with γ-cyclodextrin capped nanoparticles gave an enhanced activity of electro-optical properties yielding better display devices.

Undoubtedly, the use of metal based nanoparticle dopant in liquid crystalline materials produces favorable physicochemical impact on their display properties. Various dopants induce perturbation and polarization of the orientation pattern of liquid crystal materials, thereby, display different electro-optical properties. Among different kinds of dopants, mono- and bimetallic nanoparticles have shown interesting applicability due to their quantum size and higher surface area (Cao et al. 2010; Corain et al. 2011). On comparing both, bimetallic nanoparticles advantageously possess large and diverse surface area for inducing higher catalytic and capping abilities (Wieckowski et al. 2003). To develop such system, poly-γ-cyclodextrin has been used as capping agent for generating ZrO₂/ Au nanoparticles using ultra-sonication and microwave methods (Shiraishi et al. 2016). Different ratios of ZrO₂/Au (1:1, 2:1, 4:1, and 9:1) were used to formulate nanoparticles of different sizes (4.6 nm, 4.0 nm, 3.1 nm, and 3.1 nm, respectively) as demonstrated by dynamic light scattering (DLS) and transmission electron microscopy images. The addition of poly-γ-cyclodextrin-ZrO₂/Au dopant to NTN01 resulted in transition of isotropic phase to twisted nematic phase. Response times of twisted nematic liquid crystals obtained by mixing poly-γ-cyclodextrin-ZrO₂/Au and NTN01 were evaluated for different ratio of ZrO₂/Au. Compared to pure NTN01, Poly-γ-cyclodextrin-ZrO₂/Au doped twisted nematic liquid crystal exhibited enhanced response time, illustrating the structural diversity effect of poly-γ-cyclodextrin and ZrO₂/Au particles on liquid crystalline behavior. Further, improved response rate was observed for ZrO₂/Au (4:1) ratio compared to lower ratios of ZrO₂/Au (2:1) and ZrO₂/Au (1:1) ratios. Thus, developing better liquid crystal displays by doping available liquid crystals with different dopants would be an advantageous strategy for reducing ill effects of modern technologies.

7.4.3 Discrete Applications

Using a combination strategy of cyclodextrin and liquid crystals, the discrimination of enantiomers discrimination has been reported. Normally, NMR spectroscopy is the technique used to discriminate enantiomers with the help of a chiral auxiliary, by taking advantage of the diastereomeric interaction between the added chiral auxiliary and each enantiomer. In order to observe appreciable chemical shifts, strong diastereomeric interactions are required. An alternative method was developed to discriminate enantiomers using cyclodextrin (β-cyclodextrin and (2-hydroxypropyl)-β-cyclodextrin) as chiral cages in non-chiral liquid crystal solvent (Péchiné et al. 2002). The different inclusion and orientation of enantiomers in chiral cages produce significant and easily observable chemical shifts in the NMR spectra. Cromolyn was used as nematic liquid crystal phase in water and 1-deutero-1-phenylethanol was used as chiral compound with racemic and (S)-enriched species (Fig. 7.39). The NMR spectrum of racemic mixture showed 3 deuterium quadrupolar splittings when dissolved in cromolyn-β-cyclodextrin mesophase. Two inner doublets corresponding to encaged enantiomers with quadrupolar splittings were observe; the outer doublets correspond to outside cavity enantiomers. Thus, the different orientation of the encaged enantiomer in β-cyclodextrin cavity in liquid crystal phase allowed their differentiation.

Fig. 7.39

Structures of different compounds used in various studies

In another application, chiral nematic liquid crystals with helically twisted mesophase were obtained as chiral sorbent, by mixing the achiral nematic liquid crystals of 4-methoxy-4′-ethoxyazoxybenzene (MEAB) with acetyl-β-cyclodextrin as chiral auxiliary (Fig. 7.39) (Onuchak et al. 2012). Higher melting enthalpy of sorbent by 2.57% compared to 4-methoxy-4′-ethoxyazoxybenzene was observed, confirming intermolecular interactions between them in twisted mesophase. The sorption properties, including separation and thermodynamic functions of these chiral sorbent, were investigated toward different organic molecules including alkanes, cycloalkanes, camphene, limonene alcohols, heterocycles, butanediol-2,3 and aromatic molecules (Fig. 7.39). The structural and enantiomeric selectivity of investigated molecules depend upon the transition temperature range of sorbent, i.e. 95–120 °C for structural and 91–100 °C for enantiomeric, respectively. The polar and aromatic sorbates showed positive sorption contributions (δ) owing to their host guest interactions with acetyl-β-cyclodextrin. However, negative sorption contributions for other sorbates were observed, due to highly ordered structure and solvation effect between liquid crystal-cyclodextrin that hindered their interactions. Further, (+) isomers of butanediol-2,3, camphene, and limonene showed better enantioselectivity compared to (−) isomers due to a better compatibility with the D-(+)-glucopyranose units of acetyl-β-cyclodextrin in temperature window of 91–100 °C.

For biological applications, cyclodextrin are among the most suitable scaffolds owing to their biocompatibility and low cytotoxicity profile. Diosgenin (Fig. 7.39), (Final Report of the Amended Safety Assessment of Dioscorea Villosa (Wild Yam) Root Extract, 2004) a steroidal saponin, is a multifunctional molecule with numerous applications including plasma glucose (Pari et al. 2012) and cholesterol inhibitor (Gong et al. 2010), source of steroid hormones, dietary supplement and melanogenesis inhibitor (Lee et al. 2007). The bioavailability of diosgenin for medical applications is very limited due to its poor aqueous solubility; however, upon complexation with β-cyclodextrin, its solubility improves significantly. Okawara et al. (2014) used a combination of diosgenin, liquid crystalline amphipathic lipids: glyceryl monooleate and phytantriol and β-cyclodextrin, to investigate their enhanced solubility profile. Glyceryl monooleate and phytantriol exhibited self-assembled and dispersed liquid crystalline properties. The small-angle X-ray scattering analysis of glyceryl monooleate-diosgenin and phytantriol-diosgenin mixtures confirmed the formation of hexagonal and cubic mesophases of 100 and 200 nm respectively. The solubility and plasma concentration of diosgenin significantly increased upon mixing with glyceryl monooleate or phytantriol lipids illustrating enhanced permeation across intestinal mucosa. Comparatively, these effects are better for glyceryl monooleate than phytantriol, which were further enhanced upon addition of β-cyclodextrin. Pharmacokinetic analysis of oral administration of glyceryl monooleate-diosgenin- β-cyclodextrin and phytantriol-diosgenin- β-cyclodextrin to Wistar rats revealed higher diosgenin distribution across skin compared to diosgenin suspension alone with minimal undesired toxicity. Thus, these results validated the benefit of using β-cyclodextrin to enhance the drug solubility and bioavailability, resulting in better pharmacokinetics.

7.5 Conclusion

Since the first report of cyclodextrin-based thermotropic liquid crystals, over the years, several families of cyclodextrin-based liquid crystal materials have been reported. However, comparing to other types of materials, the research in developing cyclodextrin-based liquid crystal materials has been relatively slow. Overall, the design of self-assembled cyclodextrin materials can take advantages of fundamental intermolecular forces such as H-bonding, dipole-dipole interactions, as well as π-π interactions. Interestingly, the use of weaker interaction forces appears to generate materials with improved fluidity and richer phase transitions. Although native cyclodextrin molecules are incapable of forming thermotropic liquid crystals, the introduction of mesogenic groups can produce various mesophases such as nematic, smectic, and columnar. Photoresponsive systems were also obtained by conjugating azobenzene moieties to cyclodextrin scaffolds. Several polymeric liquid crystalline materials were demonstrated which possess very interesting properties. Even after all these investigations, several unanswered questions remain. More investigations are needed to tune the materials in order to be commercially viable.