6
applications has existed (Duchêne 1987, 1991; Szejtli 1988). An abundant scientific
literature has built up since the 1980s. Currently, every year, more than 2000 publications, including articles and book chapters, are devoted to cyclodextrins
(Cyclodextrin News, CycloLab Ltd., Hungary). Nowadays, these molecules still
fascinate researchers and industrials.
The objective of this chapter is to describe historical landmarks of the discovery,
exploration, and utilization of cyclodextrins. We also present some highlights of
their early industrial applications. To this end, an extensive list of data from about
500 original publications has been compiled. Although this historical chapter cannot hope to be exhaustive, it does highlight the work of those researchers who have
contributed to the knowledge of cyclodextrins throughout the 129 years of its
history.
1.2 Discovery and First Chemical Studies of Cyclodextrins
1.2.1 Discovery: 1891–1911
During experiments on the degradation and reduction of carbohydrates under the
action of ferments, Antoine Villiers, a French pharmacist and chemist, was the first
to observe in 1891 the formation of unwanted crystals with particular properties,
i.e., the formation of cyclodextrins. Among various Villiers’ biographies, those by
French (1957a), Thoma and Stewart (1965), Caesar (1968), Szejtli (1998), Loftsson
and Duchêne (2007), Kurkov and Loftsson (2013), Crini (2014), and Morin-Crini
et al. (2015) deserve particular mention.
Studying the degradation and reduction of carbohydrates, Villiers showed how
easy it was to transform starch to yield “novel crystalline dextrins” with particular
properties under the action of ferments. He first obtained a small amount of crystalline dextrins from digests of Bacillus amylobacter, i.e., Clostridium butyricum, on
potato starch under certain conditions (Villiers 1891a, b): 50 g potato starch in 1 L
of water at 100 °C subsequently seeded with Bacillus amylobacter and incubated
for several days in an oven at 40 °C. Villiers presented his results to the French
Académie des Sciences in February 1891 (Fig. 1.2). At that time, the dextrins, previously discovered in 1821, were the degradation products and/or the intermediate
decomposition products of starch through heating. For Villiers, his dextrins were
degradation products of starch. When purified by fractional precipitation, the crystals presented very different optical rotation properties and were difficult to hydrolyze any further. Iodine stains red those dextrins that had a high optical activity, and
the intensity of the stain decreased with the optical activity. The butyric ferment
caused the transformation of the starch directly into dextrin without the involvement
of intermediates such as diastases secreted by the ferment. Later, Villiers considered
his dextrins as the intermediate decomposition products of starch (Villiers 1891b).
Villiers also obtained un curieux sous-produit, i.e., a curious by-product, in small
N. Morin-Crini et al.
applications has existed (Duchêne 1987, 1991; Szejtli 1988). An abundant scientific
literature has built up since the 1980s. Currently, every year, more than 2000 publications, including articles and book chapters, are devoted to cyclodextrins
(Cyclodextrin News, CycloLab Ltd., Hungary). Nowadays, these molecules still
fascinate researchers and industrials.
The objective of this chapter is to describe historical landmarks of the discovery,
exploration, and utilization of cyclodextrins. We also present some highlights of
their early industrial applications. To this end, an extensive list of data from about
500 original publications has been compiled. Although this historical chapter cannot hope to be exhaustive, it does highlight the work of those researchers who have
contributed to the knowledge of cyclodextrins throughout the 129 years of its
history.
1.2 Discovery and First Chemical Studies of Cyclodextrins
1.2.1 Discovery: 1891–1911
During experiments on the degradation and reduction of carbohydrates under the
action of ferments, Antoine Villiers, a French pharmacist and chemist, was the first
to observe in 1891 the formation of unwanted crystals with particular properties,
i.e., the formation of cyclodextrins. Among various Villiers’ biographies, those by
French (1957a), Thoma and Stewart (1965), Caesar (1968), Szejtli (1998), Loftsson
and Duchêne (2007), Kurkov and Loftsson (2013), Crini (2014), and Morin-Crini
et al. (2015) deserve particular mention.
Studying the degradation and reduction of carbohydrates, Villiers showed how
easy it was to transform starch to yield “novel crystalline dextrins” with particular
properties under the action of ferments. He first obtained a small amount of crystalline dextrins from digests of Bacillus amylobacter, i.e., Clostridium butyricum, on
potato starch under certain conditions (Villiers 1891a, b): 50 g potato starch in 1 L
of water at 100 °C subsequently seeded with Bacillus amylobacter and incubated
for several days in an oven at 40 °C. Villiers presented his results to the French
Académie des Sciences in February 1891 (Fig. 1.2). At that time, the dextrins, previously discovered in 1821, were the degradation products and/or the intermediate
decomposition products of starch through heating. For Villiers, his dextrins were
degradation products of starch. When purified by fractional precipitation, the crystals presented very different optical rotation properties and were difficult to hydrolyze any further. Iodine stains red those dextrins that had a high optical activity, and
the intensity of the stain decreased with the optical activity. The butyric ferment
caused the transformation of the starch directly into dextrin without the involvement
of intermediates such as diastases secreted by the ferment. Later, Villiers considered
his dextrins as the intermediate decomposition products of starch (Villiers 1891b).
Villiers also obtained un curieux sous-produit, i.e., a curious by-product, in small
N. Morin-Crini et al.