Cyclodextrin

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. Since the 1970s, extensive work has been conducted by Szejtli and others exploring encapsulation by cyclodextrins and their derivatives for industrial and pharmacologic applications. ^[1]

Structure

  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.

The formation of the 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.

Synthesis

The production of cyclodextrins is relatively simple and involves treatment of ordinary starch with a set of easily available enzymes. Commonly chromatography techniques. As an alternative a "complexing agent" can be added during the enzymatic conversion step: such agents (usually organic solvents like 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.

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 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. Reportedly cyclodextrins are used in alcohol powder, a powder for mixing alcoholic drinks.

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 ability of cyclodextrins to form complexes with hydrophobic molecules has led to their usage in catenanes, by reacting the ends of the threaded guest.

The application of cyclodextrin as supramolecular carrier are also possible in organometallic reaction. The mechanism of action probably take place in the interfacial region (see L. Leclercq et al.). Wippf are also demonstrated by computational study that the reaction occur in the interfacial layer. The application of cyclodextrins as supramolecular carrier is possible in various organomettalic catalysis.

Derivatives

Both β-cyclodextrin and MβCD remove lipid rafts by removing the cholesterol from the membrane in research.

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.
• L. Leclercq, M. Sauthier, Y. Castanet, A. Mortreux, H. Bricout, E. Monflier, "Two-phase hydroformylation of higher olefins using randomly methylated α-cyclodextrin as mass transfer promoter: a smart solution for preserving the intrinsic properties of the rhodium / trisulfonated triphenylphoshine catalytic system", Adv. Synth. Catal. 2005, 347, 55.
• L. Leclercq, H. Bricout, S. Tilloy, E. Monflier, "Biphasic aqueous organometallic catalysis promoted by cyclodextrins: Can surface tension measurements explain the efficiency of chemically modified cyclodextrins?", J. Colloid Interface Sci. 2007, 307, 481.
• Sieffert N., Wipff G. Chem. Eur. J. 2007, 13, 1978–1990.
• Rodal, "Extraction of Cholesterol with Methyl--Cyclodextrin Perturbs Formation of Clathrin-coated Endocytic Vesicles"