63
Britain), and supplements. In the 2000s, the three native cyclodextrins were introduced into the generally regarded safe list of the US Food and Drug Administration
for use as a food additive (Hashimoto 2002). Now the food industry, along with the
pharmaceutical domain, is one of the sectors that consumes the most cyclodextrins, at
least in Japan.
Hinze (1981) was the first to describe the application of cyclodextrins in analytical chemistry, focusing on their use in chromatography and purification methods. At
that time, the first studies had established that cyclodextrins were interesting complexing agents, chiral selectors, and/or additives in chromatography (SmolkováKeulemansová and Krysl 1980; Hinze 1981; Smolková-Keulemansová 1982;
Sybilska and Smolková-Keulemansová 1984; Krysl and Smolková-Keulemansová
1985; Li and Purdy 1992). Cyclodextrins were first proposed for thin-layer chromatography, gel electrophoresis, gas chromatography, and liquid chromatography and
later for capillary electrophoresis, electrokinetic chromatography, and dialysis
(Armstrong 1980, 1984; Smolková-Keulemansová and Krysl 1980; SmolkováKeulemansová 1982; Hinze 1981; Cserhati et al. 1983; Ward and Armstrong 1986;
Li and Purdy 1992; Fanali 1993; Fanali et al. 1994; Schneiderman and Stalcup
2000). The first cyclodextrin-based chiral gas chromatography was published by
Smolková-Keulemansová (1982).
At the beginning of the 1980s, Armstrong laid down the fundamentals of
cyclodextrin- assisted separation science. Between 1980 and 1988, Armstrong and
his collaborators pioneered the development and optimization of analytical methods
suitable for cyclodextrin-based isomer separation. In 1984, the first chromatographic columns were marketed (Advanced Separation Technologies Inc.,
Whippany, NJ), and this led to spectacular progress in chromatography (Armstrong
1980, 1984; Hinze 1981; Ward and Armstrong 1986, 1988; Armstrong and Jin 1989;
Han and Armstrong 1989; Menges and Armstrong 1991). These chromatographic
packings consisted of cyclodextrin molecules linked to silica gel via a 6–10-atom
spacer. Both the linkage and the cyclodextrin were hydrolytically stable under highperformance liquid chromatography. Easily the most popular cyclodextrin-based
stationary phases were based on β-cyclodextrin, e.g., they have been shown to be
very effective at resolving the enantiomers of many compounds. Subsequently,
other stationary phases were developed, based on other native cyclodextrins, e.g.,
α- and γ-cyclodextrin, or derivatized cyclodextrins such as naphthyl-ethyl- carbamate
derivative. The α-cyclodextrin and γ-cyclodextrin columns, while less broadly
applicable in the reversed-phase mode than the β-cyclodextrin columns, were useful
for specific applications such as the separation of enantiomers of underivatized aromatic amino acids and substituted analogues or of polycyclic aromatic compounds
and steroid stereoisomers. The aromatic-derivatized cyclodextrin phases were used
to separate the enantiomers of many classes of compounds including pesticides,
biological compounds, drugs, and amino acids (Menges and Armstrong 1991;
Mitchell and Armstrong (2004). The chiral recognition mechanisms in analytical
separation sciences were reviewed by Scriba (2012). Li and Purdy (1992) and later
Szente and Szemán (2013) comprehensively reviewed the application of cyclodextrins in diverse fields of analytical chemistry and covered the structural aspects of
1 History of Cyclodextrins
Britain), and supplements. In the 2000s, the three native cyclodextrins were introduced into the generally regarded safe list of the US Food and Drug Administration
for use as a food additive (Hashimoto 2002). Now the food industry, along with the
pharmaceutical domain, is one of the sectors that consumes the most cyclodextrins, at
least in Japan.
Hinze (1981) was the first to describe the application of cyclodextrins in analytical chemistry, focusing on their use in chromatography and purification methods. At
that time, the first studies had established that cyclodextrins were interesting complexing agents, chiral selectors, and/or additives in chromatography (SmolkováKeulemansová and Krysl 1980; Hinze 1981; Smolková-Keulemansová 1982;
Sybilska and Smolková-Keulemansová 1984; Krysl and Smolková-Keulemansová
1985; Li and Purdy 1992). Cyclodextrins were first proposed for thin-layer chromatography, gel electrophoresis, gas chromatography, and liquid chromatography and
later for capillary electrophoresis, electrokinetic chromatography, and dialysis
(Armstrong 1980, 1984; Smolková-Keulemansová and Krysl 1980; SmolkováKeulemansová 1982; Hinze 1981; Cserhati et al. 1983; Ward and Armstrong 1986;
Li and Purdy 1992; Fanali 1993; Fanali et al. 1994; Schneiderman and Stalcup
2000). The first cyclodextrin-based chiral gas chromatography was published by
Smolková-Keulemansová (1982).
At the beginning of the 1980s, Armstrong laid down the fundamentals of
cyclodextrin- assisted separation science. Between 1980 and 1988, Armstrong and
his collaborators pioneered the development and optimization of analytical methods
suitable for cyclodextrin-based isomer separation. In 1984, the first chromatographic columns were marketed (Advanced Separation Technologies Inc.,
Whippany, NJ), and this led to spectacular progress in chromatography (Armstrong
1980, 1984; Hinze 1981; Ward and Armstrong 1986, 1988; Armstrong and Jin 1989;
Han and Armstrong 1989; Menges and Armstrong 1991). These chromatographic
packings consisted of cyclodextrin molecules linked to silica gel via a 6–10-atom
spacer. Both the linkage and the cyclodextrin were hydrolytically stable under highperformance liquid chromatography. Easily the most popular cyclodextrin-based
stationary phases were based on β-cyclodextrin, e.g., they have been shown to be
very effective at resolving the enantiomers of many compounds. Subsequently,
other stationary phases were developed, based on other native cyclodextrins, e.g.,
α- and γ-cyclodextrin, or derivatized cyclodextrins such as naphthyl-ethyl- carbamate
derivative. The α-cyclodextrin and γ-cyclodextrin columns, while less broadly
applicable in the reversed-phase mode than the β-cyclodextrin columns, were useful
for specific applications such as the separation of enantiomers of underivatized aromatic amino acids and substituted analogues or of polycyclic aromatic compounds
and steroid stereoisomers. The aromatic-derivatized cyclodextrin phases were used
to separate the enantiomers of many classes of compounds including pesticides,
biological compounds, drugs, and amino acids (Menges and Armstrong 1991;
Mitchell and Armstrong (2004). The chiral recognition mechanisms in analytical
separation sciences were reviewed by Scriba (2012). Li and Purdy (1992) and later
Szente and Szemán (2013) comprehensively reviewed the application of cyclodextrins in diverse fields of analytical chemistry and covered the structural aspects of
1 History of Cyclodextrins