Editing Cyclodextrin (section)

==Synthesis==
Cyclodextrins are prepared by [[Enzyme|enzymatic]] treatment of [[starch]].<ref name=CR>{{cite journal | vauthors = Szejtli J | title = Introduction and General Overview of Cyclodextrin Chemistry | journal = Chemical Reviews | volume = 98 | issue = 5 | pages = 1743–1754 | date = July 1998 | pmid = 11848947 | doi = 10.1021/cr970022c }}</ref><ref>{{cite journal | vauthors = Biwer A, Antranikian G, Heinzle E | title = Enzymatic production of cyclodextrins | journal = Applied Microbiology and Biotechnology | volume = 59 | issue = 6 | pages = 609–617 | date = September 2002 | pmid = 12226716 | doi = 10.1007/s00253-002-1057-x | s2cid = 12163906 }}</ref> Commonly [[cyclodextrin glycosyltransferase]] (CGTase) is employed along with α-[[amylase]]. First starch is liquified either by heat treatment or using [[Α-Amylase|α-amylase]], then [[Cyclomaltodextrin glucanotransferase|CGTase]] is added for the enzymatic conversion. CGTases produce mixtures 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.<ref>{{Cite journal| vauthors = Farahat M |date=2020-03-28|title=Enhancement of β-cyclodextrin Production and Fabrication of Edible Antimicrobial Films Incorporated with Clove Essential Oil/β-cyclodextrin Inclusion Complex|journal=Microbiology and Biotechnology Letters|volume=48|issue=1|pages=12–23|doi=10.4014/mbl.1909.09016|s2cid=216203179|url=https://zenodo.org/record/4458882|doi-access=free}}</ref> Purification of the three types of cyclodextrins takes advantage of the different water [[solubility]] of the molecules: β-CD which is poorly water-soluble (18.5&nbsp;g/L or 16.3 mM at 25&nbsp;°C) 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 "[[Chelation|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 [[Precipitation (chemistry)|precipitates]]. The [[Coordination complex|complex formation]] drives the conversion of starch towards the synthesis of the precipitated cyclodextrin, thus enriching its content in the final mixture of products. [[Wacker Chemie]] [[Aktiengesellschaft|AG]] uses dedicated enzymes, that can produce alpha-, beta- or gamma-cyclodextrin specifically. This is very valuable especially for the [[food industry]], as only alpha- and gamma-cyclodextrin can be consumed without a daily intake limit.

[[Image:Rotaxane Crystal Structure ChemComm page493 2001 commons.jpg|thumbnail|Crystal structure of a [[rotaxane]] with an α-cyclodextrin [[macrocycle]].<ref>{{cite journal |doi=10.1039/b010015n |title=Synthesis of fluorescent stilbene and tolan rotaxanes by Suzuki coupling |year=2001 | vauthors = Stanier CA, O'Connell MJ, Clegg W, Anderson HL |journal=Chemical Communications |issue=5 |pages=493–494}}</ref>]]

===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 [[hydroxypropyl]]ated derivatives.<ref name=Ullmann/> The primary alcohols can be tosylated.  The degree of derivatization is an adjustable, i.e. full methylation vs partial.<ref>{{cite journal|title=6A-O-p-Toluenesulfonyl-β-Cyclodextrin| vauthors = Brady B, Lynam N, O'Sullivan T, Ahern C, Darcy R |journal=Organic Syntheses |year=2000|volume=77|page=220|doi=10.15227/orgsyn.077.0220}}</ref>

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.<ref>{{cite journal | vauthors = Rodal SK, Skretting G, Garred O, Vilhardt F, van Deurs B, Sandvig K | title = Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles | journal = Molecular Biology of the Cell | volume = 10 | issue = 4 | pages = 961–974 | date = April 1999 | pmid = 10198050 | pmc = 25220 | doi = 10.1091/mbc.10.4.961 }}</ref>

Due to the covalent attachment of thiol groups to cyclodextrins high mucoadhesive properties can be introduced as these thiolated oligomers (''[[thiomer]]s'') 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.<ref>{{cite journal | vauthors = Kali G, Haddadzadegan S, Laffleur F, Bernkop-Schnürch A | title = Per-thiolated cyclodextrins: Nanosized drug carriers providing a prolonged gastrointestinal residence time | journal = Carbohydrate Polymers | volume = 300 | pages = 120275 | date = January 2023 | pmid = 36372469 | doi = 10.1016/j.carbpol.2022.120275 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Grassiri B, Knoll P, Fabiano A, Piras AM, Zambito Y, Bernkop-Schnürch A | title = Thiolated Hydroxypropyl-β-cyclodextrin: A Potential Multifunctional Excipient for Ocular Drug Delivery | journal = International Journal of Molecular Sciences | volume = 23 | issue = 5 | pages = 2612 | date = February 2022 | pmid = 35269753 | pmc = 8910138 | doi = 10.3390/ijms23052612 | doi-access = free }}</ref> Furthermore, thiolated cyclodextrins are actively taken up by target cells releasing their payload into the cytoplasma. The cellular uptake of various model drugs, for instance, was up to 20-fold improved by using thiolated α-cyclodextrin as carrier system.<ref>{{cite journal | vauthors = Kaplan Ö, Truszkowska M, Kali G, Knoll P, Blanco Massani M, Braun DE, Bernkop-Schnürch A | title = Thiolated α-cyclodextrin: The likely smallest drug carrier providing enhanced cellular uptake and endosomal escape | journal = Carbohydrate Polymers | volume = 316 | pages = 121070 | date = September 2023 | pmid = 37321712 | doi = 10.1016/j.carbpol.2023.121070 | doi-access = free }}</ref>