Elsevier

Carbohydrate Polymers

Volume 73, Issue 3, 1 August 2008, Pages 482-489
Carbohydrate Polymers

Synthesis and characterization of amphiphilic per-(6-thio-2,3-trimethylsilyl)cyclodextrin: Application to Langmuir film formation

https://doi.org/10.1016/j.carbpol.2007.12.031Get rights and content

Abstract

New amphiphilic cyclodextrins are synthesized by selective modification. Two synthetic strategies are investigated. Per-(6-thio-2,3-trimethylsilyl)cyclodextrins can only be obtain by synthesizing first the per-6-thio-cyclodextrin and then silylating the remaining hydroxy functions. Characterizations of the products were achieved by ESI-MS and intramolecular coupling between thiol functions was evidenced. These new compounds are shown to be amphiphilic, and form stable Langmuir–Blodgett films that can be transferred on the upstroke and the downstroke of a substrate with a transfer ratio close to unity.

Introduction

A large amount of work has been devoted to the synthesis and applications of α, β and γ cyclodextrins (CD) derivatives (Boger et al., 1978, Croft and Bartsh, 1983, Li and Purdy, 1992, Wenz, 1994). The versatility of these compounds allows applications in many areas. Bender and Komiyama (1979) extensively promoted the chemistry of CD (Chart 1) as enzyme mimic. Szejtly (1988) and Hinze (1981) focused on the applications of CD in chromatographic separation and purification. Other teams studied their ability to form inclusion complexes by insertion of organic molecules within the hydrophobic cavity of the CD (Rekharsky & Inoue, 1998). The outer surface of the CD being hydrophilic, thanks to the glucopyranose hydroxylic functions, the water-solubility of hydrophobic compounds can be improved. Drug delivery application recently used amphiphilic CD (Lin, Creminon, Perly, & Djedaini-Pilard, 1998). Modification of the physico-chemical properties (i.e. water solubility) of these compounds has been successfully achieved by regioselective modification of one side of the cyclodextrins, providing thus amphiphilic compounds. These new molecules were found to form either Langmuir–Blodgett (LB) films (Kawabata et al., 1988) or vesicles (Zhang, Ling, Coleman, Parrot-Lopez, & Galon, 1991). The required hydrophobic moiety for such applications was achieved by the use of aliphatic chains grafted onto the side geometrically corresponding either to the primary hydroxylic functions (Mazzaglia, Donohue, Ravoo, & Darcy, 2001) or to the secondary ones of the CD (Parrot-Lopez et al., 1992). It was suggested that at least 6 methylene groups per chains were necessary to provide stable LB films (Kawabata et al., 1988). However, in many cases, the transfer of the films onto a flat substrate produced results of questionable quality (Greenhall et al., 1995). The influence of the nature of the hydrophobic moieties of the CD has been scarcely studied. Indeed, siloxane-based cyclodextrins have only been studied by Coleman et al. (Eddaoudi, Baszkin, Parrot-Lopez, Boissonnade, & Coleman, 1995) who observed that (heptakis-6-O-tert-butyldimethylsilyl)-β-CD was able to form Langmuir monolayers.

A large amount of work was dedicated to the immobilization of cyclodextrin on a flat surface. Such a surface is commonly expected to act as a template for the immobilization of guest molecules with specific recognition (Spinke, Liley, Gunder, Angermaier, & Knoll, 1993). However, to be used in sensor applications, such surfaces must possess a high degree of order and packing (Ulman, 1991). One straightforward way to achieve this task is to self assemble thiolated cyclodextrins on a gold surface (Nelles et al., 1996, Weisser et al., 1996). However, lateral diffusion of such compound is limited and optimal packing was not achieved. Reinhoudt and co-workers (Beulen et al., 2000, de Jong et al., 2001) improved the adsorption of cyclodextrins derivatives onto a gold surface by changing the thiol functions into thioether groups. They noticed a large improvement of the degree of order and the packing density of the deposited cyclodextrins monolayers. A quasihexagonal lattice could be achieved as shown by AFM characterization.

The aim of this paper is to describe a new strategy to realize some cyclodextrins-modified gold surface for DNA nanochip applications using an electrochemical molecular beacon approach (Fan, Plaxco, & Heeger, 2003) where a cyclodextrin Langmuir film is transferred onto a gold surface. Thiol functions present in the subphase allow the anchoring of the film on the surface, and removal of the hydrophobic moieties release the cyclodextrin cavity for the complexation of the electroactive functions. A stem loop oligonucleotide possessing a terminal thiol and a ferrocene group could then be immobilized on the gold surface. The ferrocene tag would leave the cavity of the CD upon hybridization of a targeted sequence of the nucleotide. To achieve this task, the synthesis of new amphiphilic cyclodextrins derivatives able to form stable Langmuir–Blodgett films that can be anchored to metal surfaces was investigated. It was decided to convert secondary hydroxyl functions of the CD into siloxane groups in order to create hydrophobic moieties, which can be subsequently removed to release the cavity of the cyclodextrins for complexation purposes. The conversion of the primary hydroxyl groups into thiol functions, which are still hydrophilic, would allow the formation of chemical bonds when transferred onto gold surfaces. Two synthetic strategies will be discussed.

Section snippets

Experimental section

Triphenylphosphane (Aldrich) was purified by recrystallisation from methanol before use. DMF (SDS) was cryodistilled from CaH2. Toluene (SDS) was freshly distilled from metallic sodium. Trimethylsilylimidazol (tMSI), thiourea and iodine were purchased from Aldrich and used without further purification. Cyclodextrins provided by Wacker Chemie were dried under vacuum at 80 °C for 48 h prior use. All reagents were of the best commercial available quality.

NMR spectra were recorded with a Bruker

Results and discussion

The synthesis of 5α, 5β and 5γ was attempted through two paths, as described in Scheme 1. Both steps require the synthesis of per-6-deoxy-6-iodo-CD (2α, 2β and 2γ) as first precursor.

Conclusion

New modified cyclodextrins in which the primary hydroxyl side is changed into thiol, and secondary hydroxyl side is modified with trimethylsilyl groups have been synthesized. This modification with a short organo-silicon group is sufficient to confer to the new molecules an amphiphilic character. Indeed, the modified cyclodextrins form stable monolayer at the air–water interface which can be transferred onto solid substrates. This result would enable us to show that the deposit imparts to the

Acknowledgment

This work was supported by the French Research Ministery (ACI no 4154 CDR4).

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