**4. CD-dye complexes in biology and medicine**

CD systems have been extensively studied in biology and medicine, because CD counterpart acts like a comparable protein structure, providing the proper environment and arrangement of the substrates. In some cases, the processes taking place in these systems mimic those occurring in living organisms.

A novel approach towards controlled ligand–DNA interactions has been developed based on supramolecular complex of dye **9** and HP-β-CD [48]. Dye **9** is not able to coordinate with DNA (**Figure 15**). The irradiation of encapsulated **9** caused the electrocyclic transformation to product **10** which could not be able to be bound with HP-β-CD but easily interacts with DNA. Thus, the process begins with photoinduced in situ generations of a DNA ligand from the encapsulated styryl heterocycle,

#### **Figure 15.**

*Association and redistribution equilibria of ligands 9 and 10 in the presence of hosts.*

continues with the association of the ligand with the nucleic acid, and ends with the removal of the bound ligand from the DNA binding site using CB[7]. Despite the simultaneous presence of several host molecules, HP-β-CD, CB[7] and DNA, each step of the transformation cascade is not affected by the presence of other components. It is important to note that the phototransformation of precursor **9** into DNA intercalator **10** inside the cyclodextrin cavity significantly increases the biocompatibility of the method.

Molecules like cyclodextrins can be applied to solve both the solubility and the toxicity of the fluorescent dyes using in fluorescence imaging techniques to visualize and monitor specific biological targets or processes in living systems. Thus, Alexandru Rotaru and co-authors demonstrated a low level of fluorescent dye **11** toxicity (**Figure 16**) by the formation of cyclodextrin inclusion complex resulting in the successful application in cell staining [49]. Applications of this type of compound are limited due to high toxicity and water solubility problems. The addition of β-CD to dye **11** solutions in ratio of 3:1 results in dye being soluble in water. Also, fluorescent indolizinyl-pyridinium salt/β-cyclodextrin inclusion complexes demonstrated absence of cytotoxicity. Due to found in experiments cellular permeability, long-lived intracellular fluorescence and selective accumulation within acidic organelles, the dye **11** can be identified as remarkable candidate for intracellular labelling of acidic organelles (lysosomes or mitochondria).

Nanosponges prepared based on β-cyclodextrin and diphenyl carbonate have the capacity to interact with small molecules in their matrix [50]. Flavonoid quercetin was loaded into such nanosponges (**Figure 17**) [51]. The dissolution of the quercetin

**Figure 16.** *Structure of fluorescent dye 11.*

*Cyclodextrins as Supramolecular Hosts for Dye Molecules DOI: http://dx.doi.org/10.5772/intechopen.107042*

**Figure 17.**

*Structures of quercetin and nanosponge.*

**Figure 18.** *Complex of substituted β-CD dimer and Fe(II)TPPS.*

nanosponges was significantly higher compared with the pure drug. The stability of encapsulated quercetin nanosponge was markedly improved. In addition, the antioxidant activity of the quercetin in composition of nanosponges was higher than pure quercetin.

Supramolecular ensembles of porphyrinoid-CD are formed both through covalent binding and through the formation of inclusion complexes [27]. Such systems are biomimetics that mimic the natural breakdown of carotenoids [52], cytochrome P450 mediated hydroxylation [53], and oxygen binding by hemoglobin [54].

The system reversibly bound O2 was proposed by Zhou and Groves [55], it is based on self-assembly of the Fe(II)-tetra(*p*-sulfophenyl)porphyrin (**Fe(II)TPPS**) and β-CD derivative having pyridylmethyl moiety and PEG groups. Pyridyl moiety served as a ligand for **Fe(II)TPPS** and PEG chains spanned over the porphyrin surface, protecting the second binding site. The binding of O2 and CO was proved by optical method.

Another analytical method has been used by Koji Kano and his coworkers [56]. Their systems contained substituted β-CD dimers and **Fe(II)TPPS** (**Figure 18**). 4-Sulfonatophenyl groups of porphyrins were embedded in β-CD moieties of the dimer, whereas the pyridine linker coordinated the Fe(II) central ion. The hydrophobic environment within the Fe(II) ionic centre of the supramolecular complex was crucial for the efficient O2 binding, this is why the affinity of such complexes to O2 is high and stabilities of O2 adducts are significant.

Porphyrinoids are widely used as photosensitizers in photodynamic therapy (PDT), the PDT method is a promising way to treat cancer. Complexation with CD improves the photosensitizing properties of porphyrinoids since an increase in their quantum yield of singlet oxygen is observed in such complexes. This fact is of great importance for PDT [27]. The complex formation with HP-β-CD improves the efficacy of PDT for the treatment of G361 malign melanoma by using zinc-tetra(*p*sulfophenyl)porphyrin **ZnTPPS4** [57]. Thus, after 24 h incubation of cell cultures with 10<sup>l</sup> M **ZnTPPS4** and 1 mM HP-β-CD, the cells were irradiated for 7.5 min at the total irradiation dose of 12.5 J cm<sup>2</sup> which gave rise to DNA damage.

Innovative drug delivery system was proposed based on gold nanoparticles covered by cationic poly(cyclodextrin) (P(CD+)) and alginate (alg) layers [58]. 4-Hydroxy-tamoxifen was placed in the nanocapsules'shell via inclusion with the cyclodextrin cavities. It was also demonstrated that 4-hydroxy tamoxifen can be efficiently delivered to podocytes *in vitro* using CD-containing nanocapsules as carriers.

Tetrazines functionalized with adamantane groups and naphthalimide antennas can form supramolecular complex with β-cyclodextrin (β-CD) in aqueous solutions [59]. The organic anchoring groups and the tetrazine itself fit well the requirements for cavity cyclodextrin inclusion. This approach was applied for development of biosensors with electrochemical and fluorescence properties [60]. Tetrazine derivatives were immobilized at the electrogenerated polypyrrole-β-CD film through the hostguest interactions between tetrazine derivatives and β-CD. This new original molecular architecture allows the immobilization of glucose oxidase modified by β-CD (**Figure 19**). The absorption band at 425 nm in UV–Vis spectra recorded for ITO

electrodes belonging to naphthalimide fragment confirmed the formation of assembly. The oxidation of glucose in presence of oxygen with the concomitant production of H2O2 was investigated by electrochemistry. The prepared electrodes were thus maintained at 0.7 V in presence of glucose to detect, through its oxidation, the enzymatically generated H2O2.
