Chemical structure of the three main types of cyclodextrins.

Cyclodextrins (sometimes called cycloamyloses) make up a family of cyclic oligosaccharides, composed of 5 or more α-D-glucopyranoside units linked 1->4, as in amylose (a fragment of starch). The 5-membered macrocycle is not natural. Recently, the largest well-characterized cyclodextrin contains 32 1,4-anhydroglucopyranoside units, while as a poorly characterized mixture, even at least 150-membered cyclic oligosaccharides are also known. Typical cyclodextrins contain a number of glucose monomers ranging from six to eight units in a ring, creating a cone shape. thus denoting: Image File history File links Cyclodextrin. ... Image File history File links Cyclodextrin. ... The term “oligosaccharide” refers to a short chain of sugar molecules (“oligo” means “few” and “saccharide” means “sugar. ... Amylose (CAS# 9005-82-7) is a linear polymer of glucose linked with mainly α(1→4) bonds. ... Starch (CAS# 9005-25-8) is a complex carbohydrate which is insoluble in water; it is used by plants as a way to store excess glucose. ...

• α-cyclodextrin: six sugar ring molecule
• β-cyclodextrin: seven sugar ring molecule
• γ-cyclodextrin: eight sugar ring molecule

Cyclodextrins are produced from starch by means of enzymatic conversion. Over the last few years they have found a wide range of applications in food, pharmaceutical and chemical industries as well as agriculture and environmental engineering. It is also the chief active compound found in Procter and Gamble's deodorizing product "Febreze". Starch (CAS# 9005-25-8) is a complex carbohydrate which is insoluble in water; it is used by plants as a way to store excess glucose. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Procter & Gamble Co. ... A bottle of Febreze. ...

History of cyclodextrins

Cyclodextrins, as they are known today, were called "cellulosine" when first described by A. Villiers in 1891. Soon after, F. Schardinger identified the three naturally occurring cyclodextrins -α, -β, and -γ. These compounds were therefore referred to as "Schardinger sugars". For 25 years, between 1911 and 1935, Pringsheim in Germany was the leading researcher in this area, demonstrating that cyclodextrins formed stable aqueous complexes with many other chemicals. By the mid 1970's, each of the natural cyclodextrins had been structurally and chemically characterized and many more complexes had been studied. Year 1891 (MDCCCXCI) was a common year starting on Thursday (link will display the full calendar) of the Gregorian calendar (or a common year starting on Saturday of the 12-day slower Julian calendar). ... 1911 (MCMXI) was a common year starting on Sunday (link will display the full calendar). ... 1935 (MCMXXXV) was a common year starting on Tuesday (link will display full calendar). ...

Synthesis

The production of cyclodextrins is relatively simple and involves treatment of ordinary starch with a set of easily available enzymes. Commonly cyclodextrin glycosyltransferase (CGTase) is employed along with α-amylase. First starch is liquified either by heat treatment or using α-amylase, then CGTase is added for the enzymatic conversion. CGTases can synthesize all forms of cyclodextrins, thus the product of the conversion results in a mixture of the three main types of cyclic molecules, in ratios that are strictly dependent on the enzyme used: each CGTase has its own characteristic α:β:γ synthesis ratio. Purification of the three types of cyclodextrins takes advantage of the different water solubility of the molecules: β-CD which is very poorly water soluble (18.5 g/l or 16.3mM) (at 25C???) can be easily retrieved through crystallization while the more soluble α- and γ-CDs (145 and 232 g/l respectively) are usually purified by means of expensive and time consuming chromatography techniques. As an alternative a "complexing agent" can be added during the enzymatic conversion step: such agents (usually organic solvents like toluene, acetone or ethanol) form a complex with the desired cyclodextrin which subsequently precipitates. The complex formation drives the conversion of starch towards the synthesis of the precipitated cyclodextrin, thus enriching its content in the final mixture of products. The precipitated cyclodextrin is easily retrieved by centrifugation and is later separated from the complexing agent. CGTase ribbon diagram Cyclodextrin glycosyl transferase or CGTase for short (EC 2. ... Amylase is the name given to glycoside hydrolase enzymes that break down starch into glucose molecules. ... Frost crystallization on a shrub. ... Pictured is a sophisticated gas chromatography system. ... Toluene, also known as methylbenzene or phenylmethane is a clear, water-insoluble liquid with the typical smell of paint thinners, redolent of the sweet smell of the related compound benzene. ... The chemical compound acetone (also known as propanone, dimethyl ketone, 2-propanone, propan-2-one and β-ketopropane) is the simplest representative of the ketones. ... Grain alcohol redirects here. ...

Structure

Three dimensional representation of β-cyclodextrin.

γ-CD toroid structure showing spatial arrangement of the glucose monomers.

Typical cyclodextrins are constituted by 6-8 glucopyranoside units, can be topologically represented as toroids 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 not hydrophobic, but considerably less hydrophilic than the aqueous environment and thus able to host other hydrophobic molecules. On the contrary the exterior is sufficiently hydrophilic to impart cyclodextrins (or their complexes) water solubility. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... Functional group of an alcohol molecule. ... In chemistry, hydrophobic or lipophilic species, or hydrophobes, tend to be electrically neutral and nonpolar, and thus prefer other neutral and nonpolar solvents or molecular environments. ... The adjective hydrophilic describes something that likes water (from Greek hydros = water; philos = friend). ...

The formation of the inclusion compounds greatly modifies the physical and chemical properties of the host molecule, mostly in terms of water solubility. This is the reason why cyclodextrins have attracted much interest in many fields, especially pharmaceutical applications: because 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. In most cases the mechanism of controlled degradation of such complexes is based on pH change of water solutions, leading to the cleavage of hydrogen or ionic bonds between the host and the guest molecules. Alternative means for the disruption of the complexes take advantage of heating or action of enzymes able to cleave α-1,4 linkages between glucose monomers. In host-guest chemistry an inclusion compound is a complex in which one chemical compound the host forms a cavity which molecules of a second compound the guest are located. ... The correct title of this article is . ...

Uses

Cyclodextrins are able to form host-guest complexes with hydrophobic molecules given the unique nature imparted by their structure. As a result these molecules have found a number of applications in a wide range of fields. Other than the above mentioned pharmaceutical applications for drug release, cyclodextrins can be employed in environmental protection: these molecules can effectively immobilise inside their rings toxic compounds, like trichloroethane or heavy metals, or can form complexes with stable substances, like trichlorfon (an organophosphorus insecticide) or sewage sludge, enhancing their decomposition. In the food industry cyclodextrins are employed for the preparation of cholesterol free products: the bulky and hydrophobic cholesterol molecule is easily lodged inside cyclodextrin rings that are then removed, leaving behind a "low fat" food. Other food applications further include the ability to stabilize volatile or unstable compounds and the reduction of unwanted tastes and odour. The strong ability of complexing fragrances can also be used for another purpose: first dry, solid cyclodextrin microparticles are exposed to a controlled contact with fumes of active compounds, then they are added to fabric or paper products. Such devices are capable of releasing fragrances during ironing or when heated by human body. Such a device commonly used is a typical 'dryer sheet'. The heat from a clothes dryer releases the fragrance into the clothing. The chemical compound 1,1,1-trichloroethane is a chlorinated hydrocarbon that was until recently widely used as an industrial solvent. ... A heavy metal is any of a number of higher atomic weight elements, which has the properties of a metallic substance at room temperature. ... Trichlorfon is an organophosphate acetylcholinesterase inhibitor. ... An organophosphate (sometimes abbreviated OP) is the general name for esters of phosphoric acid and is one of the organophosphorus compounds. ... An insecticide is a pesticide used against insects in all developmental forms. ... Cholesterol is a sterol (a combination steroid and alcohol) and a lipid found in the cell membranes of all body tissues, and transported in the blood plasma of all animals. ... Odor receptors on the antennae of a Luna moth An odor is the object of perception of the sense of olfaction. ...

Derivatives

Both β-cyclodextrin and 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. Methyl-β-cyclodextrin are employed for the preparation of cholesterol-free products: the bulky and hydrophobic cholesterol molecule is easily lodged inside cyclodextrin rings that are then removed. It is also employed to disrupt lipid rafts by removing the cholesterol from the membrane in research. Cholesterol is a sterol (a combination steroid and alcohol) and a lipid found in the cell membranes of all body tissues, and transported in the blood plasma of all animals. ... Lipid rafts are cholesterol-rich microdomains in cell membranes. ...

References

• Villiers A., Sur la transformation de la fécule en dextrine par le ferment butyrique, Compt. Rend. Fr. Acad. Sci. 1891:435-8
• Biwer A, Antranikian G, Heinzle E. Enzymatic production of cyclodextrins. Appl Microbiol Biotechnol 2002;59:609-17. PMID 12226716.

Rodal, "Extraction of Cholesterol with Methyl--Cyclodextrin Perturbs Formation of Clathrin-coated Endocytic Vesicles"

External links

• Cyclolab Ltd.
• CTD, Inc, Cyclodextrin Resource
• welsch & partner - scientific miltimedia: beta-cyclodextrin 3D view and pdb-file