Toward the Supramolecular Cyclodextrin Dimers Using Nucleobase Pairs

Abstract

The synthesis of eleven new cyclodextrin derivatives having nucleobase moiety -thymin-1-yl, adenin-9-yl, and guanin-9-yl -is described. These two moieties are linked by different spacers, such as aminoethyl and 1,2,3-triazolyl group. Direct nucleophilic substitution and 1,3-dipolar cycloaddition were performed in good yields (13-73%) for some of the synthesized compounds. Cyclodextrins (CDs) are versatile macrocyclic maltooligosaccharides composed of a-(1→4)-linked D-glucopyranose units in 4 C 1 chair conformation and are produced from starch by enzymatic conversion in nature. The most common CDs have six, seven, and eight D-glucopyranose units and are referred to as a-, b-, and g-CD, respectively. In the case of b-CD, the polyhydroxylated compound has got a primary face of 7 hydroxy groups and a secondary face of 14 hydroxy groups. As a consequence of the structure, the molecule is hydrophilic and features a conical cavity that is essentially hydrophobic in nature. It is well known that CDs can form inclusion complexes with a variety of guest molecules due to its unique hydrophobic cup-like structure. Among these properties, the ability to form drug carrier, 1-3 separation reagents, 4-6 enzyme mimics, 7,8 photochemical sensors, 9,10 catalysis, 11,12 host-guest interactions, 13 and molecular recognition 14 are probably the most commercially valuable. Compared to CD monomers, the bridged bis(b-CD) derivatives with functional linkers have two hydrophobic cavities in a close proximity constituting an improved development. 15 This property may afford distinctly different association abilities and molecular selectivities. 16 Various structural architectures of covalent CD dimers could be prepared, but one challenge will be to obtain supramolecular CD dimers with noncovalent interactions such as H bonding, staking, electrostatic, and charge-transfer interactions. The equilibrium between the noncovalent dimers and the corresponding monomers could permit modulation of association. To the best of our knowledge, these molecular organization behaviors have not been extensively investigated. 17 The supramolecular assembly could be obtained by association of nucleobases such as adenine and thymine or guanine and cytosine. Few examples of CD derivatives having nucleobase were described in the literature, but only the study of CD monomers were reported. 18-23 As previously reported by Len's group, 18 the apparent association constant between two nucleobases appended permethylated cyclodextrin derivatives was determined by NMR in CDCl 3 . The self-assembly property of CD derivatives 13b and 14b was K TT = 22 M -1 and K AA = 16 M -1 respectively. The association constant for heterodimerization of 13b and 14b in a 1:1 stoichiometry was K AT = 385 M -1 supporting the formation of supramolecular heterodimer of modified cyclodextrins. The presence of bulky CDs did not perturb the interactions between nucleobases. In this paper, we report our contribution regarding the synthesis of different CD monomers having a nucleobase such as ad...