Beta-Cyclodextrin Duplexes That Are Connected through Two Disulfide Bonds: Potent Hosts for the Complexation of Organic Molecules

0383761 - ÚOCHB 2013 RIV DE eng J - Journal Article
Grishina, Anastasia - Stanchev, Stancho - Kumprecht, Lukáš - Buděšínský, Miloš - Pojarová, Michaela - Dušek, Michal - Rumlová, Michaela - Křížová, Ivana - Rulíšek, Lubomír - Kraus, Tomáš
Beta-Cyclodextrin Duplexes That Are Connected through Two Disulfide Bonds: Potent Hosts for the Complexation of Organic Molecules.
Chemistry - A European Journal. Roč. 18, č. 39 (2012), s. 12292-12304. ISSN 0947-6539. E-ISSN 1521-3765
Grant - others:AV ČR(CZ) M200550904
Institutional support: RVO:61388963 ; RVO:68378271
Keywords : cucurbiturils * cyclodextrins * duplexes * host-guest systems * sulfur
Subject RIV: CF - Physical ; Theoretical Chemistry
Impact factor: 5.831, year: 2012

New tubular host molecules, which are composed of two beta-cyclodextrin macrocycles that are connected through two disulfide bonds, have been prepared by the air-promoted oxidation of 6I,6IV-dideoxy-6I,6IV-disulfanyl-beta-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 Ka values were in the range 107-108M-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.
Permanent Link: http://hdl.handle.net/11104/0213602