Despite numerous attempts, Adolf von Baeyer was unable to isolate or characterize
the products from this reaction, describing them simply as a substance resembling
cement. Subsequently, Leo Baekeland (1905–1909) developed a method for synthesizing phenolic plastic from phenol and formaldehyde in an alkaline medium. Due to
the growing interest in this material, Zinke and Ziegler (1942) analyzed that
the products of the condensation reaction of alkylphenol and formaldehyde may
be the tetramers in the presence of NaOH. In 1955, Sir John Cornforth studied these
tetramers and found that there were four different conformational isomers. Finally,
Gutsche’s research indicated that these polymers were cyclic homologs, typically
tetramers, hexamers, and octamers, while odd species such as pentamers and heptamers were present in small amounts. Thus, Gutsche and colleagues explored the
experimental conditions for the synthesis of common calixarene macrocycles and
finally determined various reaction conditions for adjusting the synthesis products,
such as the type of base, the source of formaldehyde, solvent, and temperature.
It should be mentioned that the research of calixarene chemistry in China began in
the 1980s, pioneered by Prof. Zhi-Tang Huang (1928–2016) [4].
8.3
Calixarene Decoration
The general structure of calix[n]arene is shown in Fig. 2, wherein the number of
phenolic units is 4–20. However, the most studied members are those constituted by
4–8 aromatic units. Calixarenes have good chemical stability, high melting point,
adjustable cavity size, and other unique physical and chemical properties, and they
can be functionalized on demand [5]. For example, after modification by ionic
groups, the resultant calixarene derivatives can reach high water solubility, allowing
their potential for applications in supramolecular medicine to be considered.
The chemical modification of calix[n]arenes has been thoroughly investigated
with the main aim of synthesizing hosts with novel supramolecular properties. The
easiest and most common transformations regard:
• The para position of the aromatic rings (the upper, wide, or exo rim) by aromatic
electrophilic substitution (carboxylates, phosphates, guanidiniums, ammonium
groups, sulfonate functionalities, etc.)
• Phenolic hydroxyl groups (the lower, narrow, or endo rim) through alkylation and
acylation reactions
• Methylene bridges
• Aromatic walls
The chemistry of the modification of the calix[n]arenes has been widely reviewed
(Fig. 3) [6, 7]. Two particularly relevant modification types may be important in
medical applications: (a) preparation of water-soluble derivatives used as transport
molecules for molecules relevant to supramolecular medicine and (b) synthesis of
amphiphilic derivatives used to prepare self-assembling systems such as micelles,
liposomes, or solid lipid nanoparticles.
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J. Gao and D.-S. Guo
the products from this reaction, describing them simply as a substance resembling
cement. Subsequently, Leo Baekeland (1905–1909) developed a method for synthesizing phenolic plastic from phenol and formaldehyde in an alkaline medium. Due to
the growing interest in this material, Zinke and Ziegler (1942) analyzed that
the products of the condensation reaction of alkylphenol and formaldehyde may
be the tetramers in the presence of NaOH. In 1955, Sir John Cornforth studied these
tetramers and found that there were four different conformational isomers. Finally,
Gutsche’s research indicated that these polymers were cyclic homologs, typically
tetramers, hexamers, and octamers, while odd species such as pentamers and heptamers were present in small amounts. Thus, Gutsche and colleagues explored the
experimental conditions for the synthesis of common calixarene macrocycles and
finally determined various reaction conditions for adjusting the synthesis products,
such as the type of base, the source of formaldehyde, solvent, and temperature.
It should be mentioned that the research of calixarene chemistry in China began in
the 1980s, pioneered by Prof. Zhi-Tang Huang (1928–2016) [4].
8.3
Calixarene Decoration
The general structure of calix[n]arene is shown in Fig. 2, wherein the number of
phenolic units is 4–20. However, the most studied members are those constituted by
4–8 aromatic units. Calixarenes have good chemical stability, high melting point,
adjustable cavity size, and other unique physical and chemical properties, and they
can be functionalized on demand [5]. For example, after modification by ionic
groups, the resultant calixarene derivatives can reach high water solubility, allowing
their potential for applications in supramolecular medicine to be considered.
The chemical modification of calix[n]arenes has been thoroughly investigated
with the main aim of synthesizing hosts with novel supramolecular properties. The
easiest and most common transformations regard:
• The para position of the aromatic rings (the upper, wide, or exo rim) by aromatic
electrophilic substitution (carboxylates, phosphates, guanidiniums, ammonium
groups, sulfonate functionalities, etc.)
• Phenolic hydroxyl groups (the lower, narrow, or endo rim) through alkylation and
acylation reactions
• Methylene bridges
• Aromatic walls
The chemistry of the modification of the calix[n]arenes has been widely reviewed
(Fig. 3) [6, 7]. Two particularly relevant modification types may be important in
medical applications: (a) preparation of water-soluble derivatives used as transport
molecules for molecules relevant to supramolecular medicine and (b) synthesis of
amphiphilic derivatives used to prepare self-assembling systems such as micelles,
liposomes, or solid lipid nanoparticles.
204
J. Gao and D.-S. Guo