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Chemistry (Weinheim an der Bergstrasse, Germany)

β-Cyclodextrin duplexes that are connected through two disulfide bonds: potent hosts for the complexation of organic molecules.


PMID 22915339

Abstract

New tubular host molecules, which are composed of two β-cyclodextrin macrocycles that are connected through two disulfide bonds, have been prepared by the air-promoted oxidation of 6(I),6(IV)-dideoxy-6(I),6(IV)-disulfanyl-β-cyclodextrin in aqueous solution. This reaction leads to three products: monomeric intramolecular disulfide and two dimeric species, which are termed as "non-eclipsed" and "eclipsed" cyclodextrin duplexes. Oxidation at a concentration of the starting thiol of 0.1 mM gave the intramolecular disulfide as the major product whereas a concentration in the millimolar range afforded the dimeric species as the dominant products. The tubular structure of the "non-eclipsed" isomer was unequivocally determined by X-ray analysis. The binding affinities of the duplexes to a wide range of compounds, including fluorescent dyes and clinically used drugs Imatinib and Esomeprazol, were studied in water by ITC. For most guest compounds, the experimentally determined K(a) values were in the range 10(7)-10(8) M(-1). These binding affinities are significantly higher than those found in the literature for analogous complexes with native cyclodextrins. In cases of binding of neutral or anionic guest molecules cyclodextrin duplexes outperformed cucurbiturils. A complex between a duplex and Nile blue was used to investigate its ability to penetrate the cytoplasmic membrane of HeLa cells. We found that the complex accumulated in the cell membrane but did not pass into cytosol. Importantly, the complex did not decompose to a significant extent under high dilution in the cellular environment.