**4. Cyclodextrin-based supramolecular systems as chemical sensors**

Design and construction of the supramolecular architectures utilizing CD units as the key building blocks have attracted an increasing curiosity in the development of chemical sensors [39, 40]. In comparison with CD monomers, the covalently coupled CD-dimers and CD-trimers possess bigger hydrophobic cavities to accommodate the large guest molecules, which make them ideal candidates for chemical sensing. In this context, Ueno and co-workers have reported the *β*-CD dimer fluorescent sensor (**26**) in which the two *β*-CD moieties are linked through a primary face *via* dansyl group and used it to recognize steroids (**Figure 7**) [41]. The fluorescence quenching in the dansyl moiety has been observed upon the inclusion of steroid guest molecules in the hydrophobic cavities of **26**. This is due to the fact that steroid inclusion into hydrophobic cavity brings about the exclusion of dansyl moiety from hydrophobic space to aqueous hydrophilic media. In another event, Reinhoudt's group constructed *β*-CD

**Figure 7.** *Pictorial representation of the fluorescent* β*-CD-based dimers (26 and 27) and trimers (28 and 29).*

dimer-based fluorescent sensor (**27**), in which the two *β*-CD subunits are linked through secondary face *via* a dansyl moiety (**Figure 7**) and also revealed different host-guest geometries in comparison with **26** [42]. On the other hand, Kikuchi *et al.* reported the *β*-CD linear trimer-based fluorescent sensor (**28**) consisting of two dansyl moieties as linkers between three *β*-CDs, which in turn signifies the sensing event through host-guest chemistry with bile acids *viz*. cholic acid, lithocholic acid, and deoxycholic acid (**Figure 7**) [43]. On the other hand, Sasaki *et al.* have fabricated permethylated *β*-CD-based fluorescent cyclic trimer (**29**) in which *β*-CD units are bridged through biphenyl moieties (**Figure 7**). From the experimental studies, it was revealed that **29** strongly captures an anthracene derivative possessing two alkyl chains and signifies the binding event *via* fluorescence modulations [44].

Interestingly, sensing conjugates of CDs with macrocyclic hosts employing cooperative molecular recognition phenomenon have also been fabricated by various researchers across the world. In this context, Hayashita and teammates have developed a highly selective hybrid molecular conjugate (**30**) between *γ*-CD and pyrene crown ether [45, 46]. It has been noticed that in the presence of K+ ion, the emission of pyrene monomer disappears, resulting in excimer emission due to the formation of a 2:1 host-guest sandwiched complex between crown ether and K<sup>+</sup> ion (**Figure 8a**). While, Tong *et al.* have fabricated a conjugate sugar sensing system (**32**) between *β*-CD and pyrene attached boronic acid fluorophore (**Figure 8b**) [47]. Fluorescence enhancement has been noticed upon the sensing of sugar moiety by conjugate system (**32**) as can be inferred from **Figure 8b**. On the other hand, Kaneda *et al.* have constructed a sensing molecular conjugate (**35**) between methylated *α*-CD and crown

*Cyclodextrin-Based Sensors for the Recognition of Small Molecules DOI: http://dx.doi.org/10.5772/intechopen.108500*

#### **Figure 8.**

*Schematic representations of CD-based molecular sensing conjugates (a) molecular conjugate (30) of* γ*-CD with pyrene crown ether, (b) molecular conjugate (32) of* β*-CD with pyrene-functionalized boronic acid, and (c) molecular conjugate (35) of methylated* α*-CD with crown ether-functionalized azo-phenyl dye.*

ether functionalized azo-phenyl dye (**Figure 8c**) [48, 49]. Interestingly in aqueous media, a prominent color change was noticed upon the addition of 1° or 2° alkylamines to the conjugate sensing system (**35**). However, in aqueous solution, no such color changes were observed upon the addition of 3° alkylamine to **35**. The reason for color change is ascribed to the fact that 1° or 2° alkylamines are strongly bonded to crown ether moiety of **35** and their lipophilic alkyl tails construct a strong complex with the CD framework (**Figure 8c**).

The research group of Anderson has used *γ*-CD and [2]rotaxane (possessing stilbene axle and terphenylenedicarboxylic acid stoppers) for the preparation of a unique chemosensor **38** (**Figure 9**) [50]. It has been revealed that the stilbene axle of [2] rotaxane offers hydrophobic floor to *γ*-CD cavity and hence leads to an increase in its affinity to 1000-fold for appropriate guests (**39**) in comparison with simple *γ*-CD (**3**).

#### **Figure 9.**

*Schematic illustration of* γ*-CD and [2] rotaxane-based chemosensor (38) depicting sensing of a guest molecule (39)* via *fluorescence change.*

Moreover, stilbene axle of [2]rotaxane also acts as a fluorophore—signifies the sensing event through fluorescence change between chemosensor **38** and suitable guest molecule **39** (**Figure 9**).
