33
cycloamyloses might be the result of either a solvent effect or of a conformational
effect, e.g., in decarboxylation and stereoselective reactions. Bender is recognized
as the initiator of the era of biomimetic chemistry, including artificial enzymes,
molecular recognition, and bio-inspired reactivity (see his famous book: Bender and
Komiyama (1978)).
1.3.9 Complex Formation and Inclusion Compounds
In 1938, Freudenberg suggested, for the first time, the hydrophobicity of the inner
surface of the dextrin and noted how dextrins had the ability to form complexes due to
their cyclic structure (Freudenberg and Meyer-Delius 1938; Freudenberg et al. 1938).
The dextrins exhibited a complexing capacity which was discussed in connection with
the blue starch/iodine complex. For the first time, the ability of Schardinger dextrins
to form complexes was suggested. To explain these complexes, Freudenberg was the
first to show the involvement of hydrophobic forces in the formation of the complexes
(Freudenberg 1939; Freudenberg and Meyer-Delius 1939; Freudenberg et al. 1939).
Originally, however, Freudenberg was convinced that the dextrins and the amylose
helix were lined with a hydrocarbon interior, and thus the cavity of the dextrins has
been referred to as hydrocarbon in nature (Thoma and Stewart 1965; Caesar 1968;
Clarke et al. 1988; Szejtli 1998; Crini 2014; Morin- Crini et al. 2015; Crini et al. 2018).
Cramer was recognized not only for having introduced the cyclodextrin-based
nomenclature but mostly for his important work on inclusion complexes, although
they were only fully acknowledged at the end of the 1970s (Crini 2014). In 1949, in
his PhD dissertation entitled Die cyclodextrine aus Stärke, Cramer evoked for the
first time the fact that the three native cyclodextrins, considered as cylinders with
different internal diameters, were able to accommodate molecules of different sizes:
this was the first indication on their ability to form “inclusion” complexes (Cramer
1949). Two years later, Cramer published his first results on the complexes (Cramer
1951a, b, c, 1952). For instance, he observed that a number of dyes showed characteristic changes in their absorption spectra in aqueous solutions of the cyclodextrins
(Cramer 1952). Between 1952 and 1954, Cramer discovered that the toroidal form
of the cyclodextrin molecules, regarded as truncated cones, enabled them to accept
various molecules inside their cavity (Cramer 1952, 1953; Dietrich and Cramer
1954). He was the first to demonstrate the hypotheses Schardinger put forward at
the beginning of the nineteenth century on their ability to form complexes. In 1952,
Cramer adopted the term einschlussverbindungen, i.e., inclusion compound, to
characterize a complex (Cramer 1952), and later he also used the terms “occlusion
compound” and “molecular encapsulation” (Cramer and Dietsche 1959a). In 1953,
he registered his first patent where he highlighted the fact that “the formation of an
inclusion complex could modify the physical, chemical and biological characteristics of a guest molecule such as a drug” (Freudenberg et al. 1953). The inclusion
phenomena and the term einschlussverbindungen were however used by Schlenk in
1950 for the first time (Schlenk et al. 1955; French 1957a; Szejtli 1982a; Crini
1 History of Cyclodextrins
cycloamyloses might be the result of either a solvent effect or of a conformational
effect, e.g., in decarboxylation and stereoselective reactions. Bender is recognized
as the initiator of the era of biomimetic chemistry, including artificial enzymes,
molecular recognition, and bio-inspired reactivity (see his famous book: Bender and
Komiyama (1978)).
1.3.9 Complex Formation and Inclusion Compounds
In 1938, Freudenberg suggested, for the first time, the hydrophobicity of the inner
surface of the dextrin and noted how dextrins had the ability to form complexes due to
their cyclic structure (Freudenberg and Meyer-Delius 1938; Freudenberg et al. 1938).
The dextrins exhibited a complexing capacity which was discussed in connection with
the blue starch/iodine complex. For the first time, the ability of Schardinger dextrins
to form complexes was suggested. To explain these complexes, Freudenberg was the
first to show the involvement of hydrophobic forces in the formation of the complexes
(Freudenberg 1939; Freudenberg and Meyer-Delius 1939; Freudenberg et al. 1939).
Originally, however, Freudenberg was convinced that the dextrins and the amylose
helix were lined with a hydrocarbon interior, and thus the cavity of the dextrins has
been referred to as hydrocarbon in nature (Thoma and Stewart 1965; Caesar 1968;
Clarke et al. 1988; Szejtli 1998; Crini 2014; Morin- Crini et al. 2015; Crini et al. 2018).
Cramer was recognized not only for having introduced the cyclodextrin-based
nomenclature but mostly for his important work on inclusion complexes, although
they were only fully acknowledged at the end of the 1970s (Crini 2014). In 1949, in
his PhD dissertation entitled Die cyclodextrine aus Stärke, Cramer evoked for the
first time the fact that the three native cyclodextrins, considered as cylinders with
different internal diameters, were able to accommodate molecules of different sizes:
this was the first indication on their ability to form “inclusion” complexes (Cramer
1949). Two years later, Cramer published his first results on the complexes (Cramer
1951a, b, c, 1952). For instance, he observed that a number of dyes showed characteristic changes in their absorption spectra in aqueous solutions of the cyclodextrins
(Cramer 1952). Between 1952 and 1954, Cramer discovered that the toroidal form
of the cyclodextrin molecules, regarded as truncated cones, enabled them to accept
various molecules inside their cavity (Cramer 1952, 1953; Dietrich and Cramer
1954). He was the first to demonstrate the hypotheses Schardinger put forward at
the beginning of the nineteenth century on their ability to form complexes. In 1952,
Cramer adopted the term einschlussverbindungen, i.e., inclusion compound, to
characterize a complex (Cramer 1952), and later he also used the terms “occlusion
compound” and “molecular encapsulation” (Cramer and Dietsche 1959a). In 1953,
he registered his first patent where he highlighted the fact that “the formation of an
inclusion complex could modify the physical, chemical and biological characteristics of a guest molecule such as a drug” (Freudenberg et al. 1953). The inclusion
phenomena and the term einschlussverbindungen were however used by Schlenk in
1950 for the first time (Schlenk et al. 1955; French 1957a; Szejtli 1982a; Crini
1 History of Cyclodextrins