What is the chemical formula for cyclodextrin

2. Cyclodextrins viewed historically
The history of cyclodextrins can be broken down into three periods, which reflect the various stages of development in cyclodextrin research. In the period from 1891 to 1935, basic research is carried out after the discovery. But the molecular structure of the cyclodextrins remained unknown for a few decades. It was only with the knowledge of the structure of cyclodextrins from glucose units and the cyclic structure in 1936 that the next age of cyclodextrin research began, in which cyclodextrins were systematically investigated. In addition, the complex compounds of cyclodextrins were devoted to. By the end of the 1960s, research into the manufacture of cyclodextrins in particular had been carried out to such an extent that industrial production could begin. The third period, which continues to this day, is characterized by the rise of cyclodextrins from an expensive fine chemical to a product from large-scale production and the use of cyclodextrins in a variety of applications.
Discovery of the cyclodextrins
The first mention of a substance that later turns out to be a cyclodextrin is found in A. Villiers in 1891, who obtained 3 g of a crystalline substance from 1 kg of starch after adding Bacillus amylobacter to the starch. Today we are sure that this bacterial strain must have been contaminated with Bacillus macerans, because this bacterial strain produces an enzyme, the so-called cyclodextrin glycosyltransferase CGTase, which enables the formation of the cyclodextrins in the first place.
Fig. 1.12: A. Villiers obtained a colorless substance during the breakdown of starch, the crystal form of which can be clearly seen under the microscope (four times magnification)
A. Villiers calls the substance “cellulosine” because like cellulose it is quite stable against acid hydrolysis and has no reducing properties. During his investigations into the breakdown of starch by enzymes, the microbiologist F. Schardinger also received a product that is very similar to that of A. Villiers. He succeeded in isolating the bacterial strain that catalyzes the formation of cyclodextrin from starch. F. Schardinger gave it the name Bacillus macerans. By observing that the novel breakdown product of starch forms two characteristic adducts with iodine, which differ in both crystal shapes and color, he concluded that two new substances were formed during the enzymatic breakdown. Because of their origin, the new substances were called α-dextrin and β-dextrin. Neither the molecular formula nor the molecular structure were known to the discoverers A. Villiers and F. Schardinger.
Fig. 1.13: Brown crystals of the iodine-β-cyclodextrin complex under the microscope with four-fold magnification
He was able to distinguish the two dextrins from one another through the formation of the iodine adducts, because iodine forms a gray-green complex with α-cyclodextrin and a brown complex with β-cyclodextrin (see Fig. 1.13). In the years after the discovery of cyclodextrins, F. Schardinger played a key role in research on cyclodextrins. From 1911 Pringsheim and his colleagues took on the leading role in cyclodextrin research. Even if the many research results of the working group around Pringsheim lacked reliability and reproducibility in some cases, this working group was able to attribute the knowledge about the ability of cyclodextrins to form complexes with various organic substances.
Elucidation of the structure and research on cyclodextrin complexes

As early as the early 1930s, the chemists working with K. Freudenberg were able to prove that the substances known as Schardinger dextrins are made up of maltose units that are linked to one another by α-1,4-glycosidic bonds. This claim is of course not tenable for β-cyclodextrin with an odd number of glucose units. However, it can be said that the cyclodextrins are made up of glucose units which, like the two glucose molecules in maltose, are linked α-1,4-glycosidically.
It was not until 45 years after the discovery of cyclodextrins by A. Villiers that K. Freudenberg postulated that the Schardinger dextrins must have a cyclic structure. The γ-cyclodextrin, which is now industrially produced in addition to α- and β-cyclodextrin, was not even discovered until 1948.
During the intensive occupation with the production of cyclodextrins and the separation into pure fractions, cyclodextrins with more than eight glucose units were discovered.
In 1953 the first patent for the complex formation of cyclodextrins was applied for. The three researchers K. Freudenberger, F. Cramer and H. Plieninger report in the patent that molecules can be complexed in cyclodextrins, which can thereby be protected against oxidation in the air. Furthermore, the solubility of drugs can be increased by complexation, while the vapor pressure of highly volatile substances can be reduced.
These findings aroused the interest of the industry, since the most diverse areas of application for the cyclodextrin complexes could arise.
But reports of the alleged toxicity of cyclodextrins prevented advances in cyclodextrin chemistry. After two independent studies had confirmed the harmlessness of cyclodextrins, there was a rapid increase in publications on cyclodextrins.
Wacker Chemie AG has been producing cyclodextrins since the early 1980s. WACKER's newest production facility, with an annual production of more than 4,000 metric tons of cyclodextrins, is located in the US state of Iowa in close proximity to huge corn cultivation areas where the raw material corn starch for cyclodextrin production grows.

Fig. 1.14: Wacker's production facility in Eddyville Iowa (USA)
In addition to the three natural cyclodextrins, more than 100 derivatives are industrially produced and used in various areas of application. For use in the pharmaceutical sector in particular, there is still a need for derivatives that have to meet the diverse requirements in terms of properties. Above all, they must be very soluble in water, cost-effective to manufacture, be highly pure to synthesize and non-toxic. In addition, they should not decompose at high temperatures, since the medication must be sterilized. The ability to complex various active ingredients and a rapid and unproblematic metabolism are further requirements for cyclodextrin derivatives for pharmaceutical products.

Literature:

  • Szejtli, J .; Osa, T .; Comprehensive Supramolecular Chemistry. Volume 3 Cyclodextrins, Elsevier Science Ltd. Oxford, 1996, Pp. 1-4
  • Szejtli, J .; Pure Appl. Chem., 10, 2004, 76, 1825-1845
  • Szejtli, J .; Chem. Rev., 1998, 98, 1743-1753
  • Regiert, M .; Cyclodextrins: Anti-Aging Sugars; WACKER WORLD WIDE CORPORATE MAGAZINE 3/2002, 2002, 22-27
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