Selective modifications at the different positions of cyclodextrins: a review ofstrategies

Abstract

Cyclodextrins (CDs) are natural, nontoxic, and biodegradable macrocyclic oligosaccharides. As supramolecular hosts, CDs have numerous applications in many aspects. However, nonsubstituted CDs have the disadvantages of solubility, unspecific recognition sites, and weak interactions with guest molecules. Therefore, new CD-based derivatives are successfully designed, synthesized, and widely used in various fields. This contribution outlines the research progress in CD derivatives. In particular, this review emphasizes the synthesis and application of CDs modified through functionalization in definite positions, random substitution, and reconstruction of the skeleton. At the end of this review, a summary and future directions are presented.Recently CDs have a wide range of applications in cancer treatment owing to the particularity of their different ring spaces. CDs could increase the solubility of anticancer flavonoids, such as curcumin and quercetin, which are very poorly soluble in water [41,42]. A novel CD complex of curcumin had superior attributes compared with free curcumin for cellular uptake and for antiproliferative and antiinflammatory activities, preferentially aggregating in the pancreas and possessing strong anticancer activity against pancreatic or tubulin surface cancer cells [41,43]. Similarly, the solubility of quercetin could be improved linearly with the increasing molality of CDs at the same temperature [44]. Selective modifications of CDs at definite positions Monosubstitution of CDsWhen natural CDs are unsuitable for a particular application, chemists begin to modify CDs to allow their derivatives to perform their intended function. To pursue an increasingly perfect structure, the idea of monosubstituted CD derivatives was conceived. However, the direct synthesis of single-isomer CD derivatives is challenging [45]. A single substitution has three possible isomers (Figure 2).

Synthesis of Mono-Amino Substituted γ-CD: Host–Guest Complexation and In Vitro Cytotoxicity Investigation

“…In particular, the hydrophobic cavity of CDs enables them to encapsulate hydrophobic molecules of suitable sizes and generate inclusion complexes [ 4 ], which is called host–guest complexation [ 5 ]. This remarkable property of encapsulation of guest molecules is applied in many fields, including medicine, materials science, food, and agricultural industries [ 6 , 7 , 8 , 9 ]. The natural β-CD is the most commonly used CD in industrial products.…”

“…These new CDs derivatives not only retain the binding ability of guest hydrophobic small and large molecules into the hydrophobic cavity, but also introduce new interactions with substituents at the rims, which are relatively well-hydrated [ 17 ]. Currently, the most commonly applied cyclodextrin derivatives are randomly methylated β-CD, 2-hydroxypropylated-β-CD, sulfobutylether-β-CD, sulfated-β-CD, and carboxymethyl-β-CD [ 6 , 17 ]. Commercially available modified CDs are generally limited to β-CD and to a multi- or random substitution of γ-CD [ 6 ].…”

“…Currently, the most commonly applied cyclodextrin derivatives are randomly methylated β-CD, 2-hydroxypropylated-β-CD, sulfobutylether-β-CD, sulfated-β-CD, and carboxymethyl-β-CD [ 6 , 17 ]. Commercially available modified CDs are generally limited to β-CD and to a multi- or random substitution of γ-CD [ 6 ]. Random substitution of CDs is not desirable for the hosts when binding selectivity is desired.…”

Phase Transfer Catalyzed Preparation of 4-Methylbenzenesulfonyl Imidazole for Regioselective Synthesis of Mono-6-(4-methylbenzenesulfonyl)-β-cyclodextrin

“…In particular, β-cyclodextrin (β-CD) forms intramolecular hydrogen bonds between secondary OH groups at C-2 and C-3 positions which detract from hydrogen bond formation with surrounding water molecules, resulting in less negative heat of hydration and significant lowering of solubility, i.e., 18.5 g/L at 25 °C [2]. In order to improve the solubility of β-cyclodextrin in aqueous media, it is necessary to modify β-cyclodextrin by substituting one OH group at either 2or 6-position with other groups to give functionalized CD derivatives which are more soluble in water [3][4].…”

Multiple stimuli responsive cyclodextrin based smart materials for drug delivery: a review

“…Cyclodextrins (CD) are cyclic oligosaccharides composed of D-glucopyranose segments linked through Į-1, 4-glycosidic bonds [1]. CDs possess a toroidal shape with outer hydrophilic surface and inner hydrophobic cavity [2].…”