Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocycle ring of glucose subunits joined by α-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzyme conversion. They are used in food, pharmaceutical, drug delivery, and chemical industries, as well as agriculture and environmental engineering.
Cyclodextrins are composed of 5 or more α-D-glucoPyranose units linked 1 → 4, as in amylose (a fragment of starch). Typical cyclodextrins contain a number of glucose monomers ranging from six to eight units in a ring, creating a cone shape:
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α (alpha)-cyclodextrin: 6 glucose subunits
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β (beta)-cyclodextrin: 7 glucose subunits
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γ (gamma)-cyclodextrin: 8 glucose subunits
The largest well-characterized cyclodextrin contains 32 1,4-anhydroglucopyranoside units. Poorly-characterized mixtures, containing at least 150-membered cyclic oligosaccharides are also known.
Applications
Drug delivery
Cyclodextrins are ingredients in more than 30 different approved medicines.
With a hydrophobic interior and hydrophilic exterior, cyclodextrins form complexes with hydrophobic compounds. Alpha-, beta-, and gamma-cyclodextrin are all generally recognized as safe by the U.S. FDA.
[; ; ] They have been applied for delivery of a variety of drugs, including hydrocortisone, prostaglandin, nitroglycerin, itraconazole, chloramphenicol. The cyclodextrin confers solubility and stability to these drugs.
[ The inclusion compounds of cyclodextrins with hydrophobic molecules are able to penetrate body tissues, these can be used to release biologically active compounds under specific conditions.]
Chromatography
β-cyclodextrins are used to produce stationary phase media for HPLC separations.
Other
Cyclodextrins bind . Such devices are capable of releasing fragrances when heated, such as by ironing, body heat, or a dryer. A common application is a typical 'dryer sheet'. They are also the main ingredient in Febreze, which claims that the β-cyclodextrins "trap" odor-causing compounds, thereby reducing the odor.[
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Cyclodextrins are also used to produce alcohol powder by encapsulating ethanol. The powder produces an alcoholic beverage when mixed with water, or can also be taken in a pill.
Structure
Typical cyclodextrins are constituted by 6-8 glucopyranoside units. These subunits are linked by 1,4 . The cyclodextrins have toroidal shapes, with the larger and the smaller openings of the toroid exposing to the solvent secondary and primary hydroxyl groups respectively. Because of this arrangement, the interior of the toroids is considerably less hydrophilic than the aqueous environment and thus able to host hydrophobic molecules. In contrast, the exterior is sufficiently hydrophilic to impart cyclodextrins (or their complexes) water solubility. They are not soluble in typical organic solvents.
Synthesis
Cyclodextrins are prepared by Enzyme treatment of starch.
Derivatives
Interest in cyclodextrins is enhanced because their host–guest behavior can be manipulated by chemical modification of the hydroxyl groups. O-Methylation and acetylation are typical conversions. Propylene oxide gives derivatives.[ The primary alcohols can be tosylated. The degree of derivatization is an adjustable, i.e. full methylation vs partial.]
Both β-cyclodextrin and methyl-β-cyclodextrin (MβCD) remove cholesterol from cultured cells. The methylated form MβCD was found to be more efficient than β-cyclodextrin. The water-soluble MβCD is known to form soluble inclusion complexes with cholesterol, thereby enhancing its solubility in aqueous solution. MβCD is employed for the preparation of cholesterol-free products: the bulky and hydrophobic cholesterol molecule is easily lodged inside cyclodextrin rings. MβCD is also employed in research to disrupt lipid rafts by removing cholesterol from membranes.
Due to the covalent attachment of thiol groups to cyclodextrins high mucoadhesive properties can be introduced as these thiolated oligomers ( ) are capable of forming disulfide bonds with cysteine-rich subdomains of mucus glycoproteins. The gastrointestinal and ocular residence time of thiolated cyclodextrins is therefore substantially prolonged.
Research
supramolecular chemistry, cyclodextrins are precursors to mechanically interlocked molecular architectures, such as and . Illustrative, α-cyclodextrin form second-sphere coordination complex with tetrabromoaurate anion (AuBr4-).
β-Cyclodextrin complexes with certain carotenoid food colorants have been shown to intensify color, increase water solubility and improve light stability.
Complexes formed between β-cyclodextrin and adamantane derivatives have been used to make self-healing materials, such as
Using the host-guest interaction between β-Cyclodextrin and Perfluorohexane, acoustically active were created.
History
Cyclodextrins were called "cellulosine" when first described by A. Villiers in 1891.[ ] Among the processes used for complexation, the kneading process seems to be one of the best.
Safety
Cyclodextrins are of wide interest in part because they appear Toxicity in animal studies. The LD50 (oral, rats) is on the order of grams per kilogram.[ Nevertheless, attempts to use β-cyclodextrin for the prevention of atherosclerosis,]
