165
properties (Crini 2014; Crini et al. 2018). For instance, Professor Casu demonstrated three important characteristics (Crini 2014): (1) all secondary hydroxyl
groups were situated on one of the two edges of the cyclodextrin ring, whereas all
the primary ones were placed on the other edge; (2) the cavity was lined by the
hydrogen atoms and the glycosidic oxygen bridges, respectively; and (3) the C-2
and C-3 hydroxyl groups of the adjacent glucopyranose units formed hydrogen
bonds which stabilized the shape of the cyclodextrin molecule. Later, Professor
Szejtli has shown that these characteristics had a significant influence on the solubility of cyclodextrins in water (Szejtli 1982, 1988).
Professor Casu reported the infrared spectra of several cycloamyloses (Fig. 3.3)
and assigned the main individual bands (Fig. 3.4). He detailed the spectra of hydrates
of cyclohexaamylose where he observed the reduced splitting and the broadening of
the bands in the dehydrated samples with respect to the hydrated forms (Casu and
Reggiani 1964; Casu et al. 1965a). Professor Casu concluded that “it was not easy
to explain the shift of the frequencies of the ring vibrations on going from cyclohexaamylose to cycloheptaamylose to amylodextrin and amylose in terms of the
conformation of glucopyranose rings” (Casu et al. 1965a). He suggested that “the
configuration of the ring sequences and the bulkiness of the chains certainly affected
ring vibrations” (Crini 2014). He also suggested the existence in water of hydrogen
bonds between the secondary hydroxyl functions (Casu et al. 1965a).
In 1966, Professor Casu, studying the IR spectra of cycloamyloses in the amorphous solid phase and in aqueous and dimethyl sulfoxide solutions (Fig. 3.5),
showed that the C1-H bond was equatorial and the C1-O bond axial, and this was
consistent with the C-1 conformation of the glucopyranose (Casu and Reggiani
1966). The same year, Professor Casu published the first NMR spectra of cycloamyloses (Fig. 3.6). Comparing the spectra of maltose and cycloamyloses, “an interesting and curious downfield displacement of the non-anomeric hydroxyl signal below
5” was evident (Casu et al. 1966). Professor Casu also showed that
1
H-NMR spectroscopy was applicable to quantitative analysis of concentrated solutions of mixtures of cyclodextrins in dimethyl sulfoxide (Casu 1966, 1967; Casu and Reggiani
1966; Casu et al. 1966).
Using NMR of α-cyclodextrin in DMSO-d 6 through hydrogen-deuterium
exchanges of cyclodextrins, Professor Casu also demonstrated that the
D-glucopyranose units in cyclodextrins were in the C-1 chair conformation and the
primary and secondary hydroxyl groups had similar conformation to those in the
crystalline state (Casu 1966; Casu and Reggiani 1966). Both NMR and IR spectra
through hydrogen-deuterium exchanges of cyclodextrins also first showed the existence in water of hydrogen bonds between the secondary hydroxyl functions, which
brought about a slight chemical shift in the protons of these functions (Casu 1966;
Casu and Reggiani 1966). Later, Professor Casu determined the value of the deuteration equilibrium constant of the same functions (Casu 1967; Casu et al. 1968a).
The equilibrium constant for the secondary hydroxyl groups was 0.75 in
α-cyclodextrin and 0.65 in β-cyclodextrin, both much less than the corresponding
value for amylose, i.e., 0.85. This clearly indicated that intramolecular hydrogen
bonding rendered the secondary hydroxyl groups in cyclodextrins more resistant to
3 Professor Casu and Cyclodextrins
properties (Crini 2014; Crini et al. 2018). For instance, Professor Casu demonstrated three important characteristics (Crini 2014): (1) all secondary hydroxyl
groups were situated on one of the two edges of the cyclodextrin ring, whereas all
the primary ones were placed on the other edge; (2) the cavity was lined by the
hydrogen atoms and the glycosidic oxygen bridges, respectively; and (3) the C-2
and C-3 hydroxyl groups of the adjacent glucopyranose units formed hydrogen
bonds which stabilized the shape of the cyclodextrin molecule. Later, Professor
Szejtli has shown that these characteristics had a significant influence on the solubility of cyclodextrins in water (Szejtli 1982, 1988).
Professor Casu reported the infrared spectra of several cycloamyloses (Fig. 3.3)
and assigned the main individual bands (Fig. 3.4). He detailed the spectra of hydrates
of cyclohexaamylose where he observed the reduced splitting and the broadening of
the bands in the dehydrated samples with respect to the hydrated forms (Casu and
Reggiani 1964; Casu et al. 1965a). Professor Casu concluded that “it was not easy
to explain the shift of the frequencies of the ring vibrations on going from cyclohexaamylose to cycloheptaamylose to amylodextrin and amylose in terms of the
conformation of glucopyranose rings” (Casu et al. 1965a). He suggested that “the
configuration of the ring sequences and the bulkiness of the chains certainly affected
ring vibrations” (Crini 2014). He also suggested the existence in water of hydrogen
bonds between the secondary hydroxyl functions (Casu et al. 1965a).
In 1966, Professor Casu, studying the IR spectra of cycloamyloses in the amorphous solid phase and in aqueous and dimethyl sulfoxide solutions (Fig. 3.5),
showed that the C1-H bond was equatorial and the C1-O bond axial, and this was
consistent with the C-1 conformation of the glucopyranose (Casu and Reggiani
1966). The same year, Professor Casu published the first NMR spectra of cycloamyloses (Fig. 3.6). Comparing the spectra of maltose and cycloamyloses, “an interesting and curious downfield displacement of the non-anomeric hydroxyl signal below
5” was evident (Casu et al. 1966). Professor Casu also showed that
1
H-NMR spectroscopy was applicable to quantitative analysis of concentrated solutions of mixtures of cyclodextrins in dimethyl sulfoxide (Casu 1966, 1967; Casu and Reggiani
1966; Casu et al. 1966).
Using NMR of α-cyclodextrin in DMSO-d 6 through hydrogen-deuterium
exchanges of cyclodextrins, Professor Casu also demonstrated that the
D-glucopyranose units in cyclodextrins were in the C-1 chair conformation and the
primary and secondary hydroxyl groups had similar conformation to those in the
crystalline state (Casu 1966; Casu and Reggiani 1966). Both NMR and IR spectra
through hydrogen-deuterium exchanges of cyclodextrins also first showed the existence in water of hydrogen bonds between the secondary hydroxyl functions, which
brought about a slight chemical shift in the protons of these functions (Casu 1966;
Casu and Reggiani 1966). Later, Professor Casu determined the value of the deuteration equilibrium constant of the same functions (Casu 1967; Casu et al. 1968a).
The equilibrium constant for the secondary hydroxyl groups was 0.75 in
α-cyclodextrin and 0.65 in β-cyclodextrin, both much less than the corresponding
value for amylose, i.e., 0.85. This clearly indicated that intramolecular hydrogen
bonding rendered the secondary hydroxyl groups in cyclodextrins more resistant to
3 Professor Casu and Cyclodextrins