(up to 10
17 M
À1
) [11]. As a consequence of their variable sizes, CBs have selective
binding toward guests with different sizes and functional groups. Therefore, CBs are
excellent macrocyclic hosts to construct self-assembly for biomedical applications.
CBs are prepared by one-pot reaction to yield a mixture of CB homologues,
which are separated based on different solubilities in various solvents. Functionalization of CBs is relatively difficult. The general protocol is to oxidize CBs with
potassium persulfate or hydrogen peroxide. The preparation is typically low yield
and tedious to isolate. To tackle this challenge, CB derivatives have been developed,
which are prepared by multistep organic synthesis.
CB[8] could form 1:2 ternary complex with suitable guests with high binding affinity.
CB[8] is capable of encapsulating methyl viologen and 2,6-dihydroxynaphthlene simultaneously. The formation of ternary complex is due to intramolecular charge transfer
from electron-rich 2,6-dihydroxynaphthlene to electron-deficient methyl viologen. By
choosing property guests and suitable chemical modification to guests, supramolecular
cross-linking based on this ternary complex could be developed and used for selfassembly construction.
The excellent recognition property of CBs renders them the ability to encapsulate
drugs and dyes by host-guest interaction. Isaacs and co-workers prepared a biotinmodified CB[7] derivative by multistep organic synthesis. This CB[7] derivative
retains the good binding affinity of macrocyclic CBs and could encapsulate common
antitumor drug oxaliplatin [12]. Supramolecular interaction between host and
oxaliplatin is discovered to be high-affinity and kinetically stable, which render
this complex possible to be used for drug delivery purpose. Cell study indicates that
targeting effect of biotin could significantly enhance cell uptake of oxaliplatin, when
encapsulated by CB[7] derivative.
23.2.3 Calixarene
CAs are considered to be the third-generation macrocyclic host after crown ether and
CDs. The preparation of CAs involves the base-catalyzed condensation reaction of
phenol and formaldehyde with phenolic units linked by methylene bridges at the
meta-positions. CAs have variable cavity dimensions according to the number of
phenolic units. CAs with even numbers (n = 4, 6, 8) are easier to synthesize and
purify and have been widely investigated. By comparison, CAs with odd numbers
(n = 5, 7, 9) are relatively more difficult to synthesize and less frequently used.
CAs have unique unsymmetrical cone shape with an upper rim and a lower rim.
Both rims could be chemically modified to achieve desired functions. The lower rim
is featured with phenolic oxygen and a hydrophilic property. The upper rim is
hydrophobic due to the methyl groups. Therefore, guests can be encapsulated by
the cavity at both rims of CAs, which include small organic molecules, ions,
macromolecules, and so on. Various forces, including hydrophobic effect,
ion-dipole interaction, and hydrogen-bonding interaction, drive the complexation.
CAs are relatively less frequently used macrocyclic host molecules for molecular
recognition and self-assembly construction in water compared to CDs. There are
23 Stimuli-Responsive Self-Assembly Based on Macrocyclic Hosts and Biomedical. . .
607
17 M
À1
) [11]. As a consequence of their variable sizes, CBs have selective
binding toward guests with different sizes and functional groups. Therefore, CBs are
excellent macrocyclic hosts to construct self-assembly for biomedical applications.
CBs are prepared by one-pot reaction to yield a mixture of CB homologues,
which are separated based on different solubilities in various solvents. Functionalization of CBs is relatively difficult. The general protocol is to oxidize CBs with
potassium persulfate or hydrogen peroxide. The preparation is typically low yield
and tedious to isolate. To tackle this challenge, CB derivatives have been developed,
which are prepared by multistep organic synthesis.
CB[8] could form 1:2 ternary complex with suitable guests with high binding affinity.
CB[8] is capable of encapsulating methyl viologen and 2,6-dihydroxynaphthlene simultaneously. The formation of ternary complex is due to intramolecular charge transfer
from electron-rich 2,6-dihydroxynaphthlene to electron-deficient methyl viologen. By
choosing property guests and suitable chemical modification to guests, supramolecular
cross-linking based on this ternary complex could be developed and used for selfassembly construction.
The excellent recognition property of CBs renders them the ability to encapsulate
drugs and dyes by host-guest interaction. Isaacs and co-workers prepared a biotinmodified CB[7] derivative by multistep organic synthesis. This CB[7] derivative
retains the good binding affinity of macrocyclic CBs and could encapsulate common
antitumor drug oxaliplatin [12]. Supramolecular interaction between host and
oxaliplatin is discovered to be high-affinity and kinetically stable, which render
this complex possible to be used for drug delivery purpose. Cell study indicates that
targeting effect of biotin could significantly enhance cell uptake of oxaliplatin, when
encapsulated by CB[7] derivative.
23.2.3 Calixarene
CAs are considered to be the third-generation macrocyclic host after crown ether and
CDs. The preparation of CAs involves the base-catalyzed condensation reaction of
phenol and formaldehyde with phenolic units linked by methylene bridges at the
meta-positions. CAs have variable cavity dimensions according to the number of
phenolic units. CAs with even numbers (n = 4, 6, 8) are easier to synthesize and
purify and have been widely investigated. By comparison, CAs with odd numbers
(n = 5, 7, 9) are relatively more difficult to synthesize and less frequently used.
CAs have unique unsymmetrical cone shape with an upper rim and a lower rim.
Both rims could be chemically modified to achieve desired functions. The lower rim
is featured with phenolic oxygen and a hydrophilic property. The upper rim is
hydrophobic due to the methyl groups. Therefore, guests can be encapsulated by
the cavity at both rims of CAs, which include small organic molecules, ions,
macromolecules, and so on. Various forces, including hydrophobic effect,
ion-dipole interaction, and hydrogen-bonding interaction, drive the complexation.
CAs are relatively less frequently used macrocyclic host molecules for molecular
recognition and self-assembly construction in water compared to CDs. There are
23 Stimuli-Responsive Self-Assembly Based on Macrocyclic Hosts and Biomedical. . .
607