21
(Freudenberg and Cramer 1948; Cramer 1949). In 1950, French, studying the periodate oxidation of the three cycloamyloses, finally concluded that all three molecules had a cyclic structure in which each D-glucose unit was linked to the next by
an α-D-(1→4)-glucosidic bond, and the interior of the cavity was apolar (French
and McIntire 1950; Norberg and French 1950; French et al. 1950b). Schardinger
dextrins were then regarded rather as conical cylinders than cylinders, in agreement
with Cramer’s suggestion. Another interesting feature is made by French: γ-dextrin
was “a noncoplanar, more flexible structure,” and therefore, it was the “most soluble
of the three dextrins.” Later, cycloamyloses were finally regarded as truncated cones
or “capsules” by French (French 1957a), in agreement with the results published by
Cramer (Cramer 1952, 1953, 1956; Dietrich and Cramer 1954).
Cramer also contributed greatly to the molecular structural knowledge of the
Schardinger dextrins. In 1948, the young student Cramer published his first result
on Schardinger dextrins (Freudenberg and Cramer 1948). Using optical activity,
Cramer demonstrated the cyclic nature of α- and β-dextrins. The same year, he discovered γ-dextrin and suggested that the three dextrins possessed an apolar cavity.
One year later, Cramer received his PhD at Heidelberg University, under the supervision of Freudenberg (Cramer 1949). He introduced the cyclodextrin-based
nomenclature, demonstrated the cyclic nature of cyclodextrins using optical activity
data, and showed that the three cyclodextrins had different internal diameters and
each cavity was filled with water molecules (Cramer 1949). His doctoral work was
then published between 1951 and 1952 (Cramer 1951a, b, c, 1952), adding to the
previous results of Freudenberg but mostly “confirming those of French” on the
physical (cavity size) and chemical (reactivity) properties, the structure, and chemistry of cyclodextrins. For instance, investigating the configuration at the anomeric
centers by hydrolytic methods, Cramer came to the same conclusions as Karrer
(1923), Miekeley (1932), and French (French and Rundle 1942) as to the existence
of α-(1→4) glucosidic/glycosidic linkages. Cramer also published for the first time
a variety of other interesting features. Studying the molecular size of the three dextrins, he showed that a same dextrin could exist in different crystal forms. Cramer
then discovered the toroidal form of the cyclodextrin molecules, considering cyclodextrins as truncated cones or “capsules” rather than cylinders, like previously
reported by French (French et al. 1948, 1949a, b). The numbering system employed
to describe the glucopyranose rings, reported in Fig. 1.5, was then accepted, and
Cramer schematized his conclusions on the chemical structure of α-, β-, and
γ-cyclodextrins by the two schemes reported in Fig. 1.7. Cramer finally concluded
that cyclodextrins were non-reducing oligosaccharides containing 6, 7, or 8 units
linked by α-D-(1→4) bonds, having both hydrophobic and hydrophilic regions. On
the side where the secondary hydroxyl groups were situated, the diameter of the
cavity was larger than on the side with the primary hydroxyls, since free rotation of
the latter reduced the effective diameter of the cavity. Figure 1.8 illustrates the
hydrophobic and hydrophilic regions of an α-dextrin “capsule” (Cramer 1953,
1956; Dietrich and Cramer 1954).
In 1965, both Casu et al. (1965) and Hybl et al. (1965) confirmed the conclusions
published by French and Cramer on the cyclic structure of cyclodextrin and its
1 History of Cyclodextrins
(Freudenberg and Cramer 1948; Cramer 1949). In 1950, French, studying the periodate oxidation of the three cycloamyloses, finally concluded that all three molecules had a cyclic structure in which each D-glucose unit was linked to the next by
an α-D-(1→4)-glucosidic bond, and the interior of the cavity was apolar (French
and McIntire 1950; Norberg and French 1950; French et al. 1950b). Schardinger
dextrins were then regarded rather as conical cylinders than cylinders, in agreement
with Cramer’s suggestion. Another interesting feature is made by French: γ-dextrin
was “a noncoplanar, more flexible structure,” and therefore, it was the “most soluble
of the three dextrins.” Later, cycloamyloses were finally regarded as truncated cones
or “capsules” by French (French 1957a), in agreement with the results published by
Cramer (Cramer 1952, 1953, 1956; Dietrich and Cramer 1954).
Cramer also contributed greatly to the molecular structural knowledge of the
Schardinger dextrins. In 1948, the young student Cramer published his first result
on Schardinger dextrins (Freudenberg and Cramer 1948). Using optical activity,
Cramer demonstrated the cyclic nature of α- and β-dextrins. The same year, he discovered γ-dextrin and suggested that the three dextrins possessed an apolar cavity.
One year later, Cramer received his PhD at Heidelberg University, under the supervision of Freudenberg (Cramer 1949). He introduced the cyclodextrin-based
nomenclature, demonstrated the cyclic nature of cyclodextrins using optical activity
data, and showed that the three cyclodextrins had different internal diameters and
each cavity was filled with water molecules (Cramer 1949). His doctoral work was
then published between 1951 and 1952 (Cramer 1951a, b, c, 1952), adding to the
previous results of Freudenberg but mostly “confirming those of French” on the
physical (cavity size) and chemical (reactivity) properties, the structure, and chemistry of cyclodextrins. For instance, investigating the configuration at the anomeric
centers by hydrolytic methods, Cramer came to the same conclusions as Karrer
(1923), Miekeley (1932), and French (French and Rundle 1942) as to the existence
of α-(1→4) glucosidic/glycosidic linkages. Cramer also published for the first time
a variety of other interesting features. Studying the molecular size of the three dextrins, he showed that a same dextrin could exist in different crystal forms. Cramer
then discovered the toroidal form of the cyclodextrin molecules, considering cyclodextrins as truncated cones or “capsules” rather than cylinders, like previously
reported by French (French et al. 1948, 1949a, b). The numbering system employed
to describe the glucopyranose rings, reported in Fig. 1.5, was then accepted, and
Cramer schematized his conclusions on the chemical structure of α-, β-, and
γ-cyclodextrins by the two schemes reported in Fig. 1.7. Cramer finally concluded
that cyclodextrins were non-reducing oligosaccharides containing 6, 7, or 8 units
linked by α-D-(1→4) bonds, having both hydrophobic and hydrophilic regions. On
the side where the secondary hydroxyl groups were situated, the diameter of the
cavity was larger than on the side with the primary hydroxyls, since free rotation of
the latter reduced the effective diameter of the cavity. Figure 1.8 illustrates the
hydrophobic and hydrophilic regions of an α-dextrin “capsule” (Cramer 1953,
1956; Dietrich and Cramer 1954).
In 1965, both Casu et al. (1965) and Hybl et al. (1965) confirmed the conclusions
published by French and Cramer on the cyclic structure of cyclodextrin and its
1 History of Cyclodextrins