anticancer activities [95–97]. However, bioapplication of C 60 is largely limited by its
poor water solubility. To overcome this disadvantage, Zhang and coworkers
designed and synthesized a bis-αCD-C 60 conjugate (Fig. 22a) using αCDs as
carriers, after a selective deprotection reaction on the second rim to give monolCD, followed by a coupling reaction to produce a CD dimer, which, via
Bingel–Hirsch cyclopropanation, provided the bis-αCD-C 60 conjugate. This
functionalized strategy tremendously enhanced the water solubility of C 60 from
1.3 Â 10
À11 to 0.5 mg/mL. On the basis of a similar concept, they also synthesized
two other species of bis-γCD-C 60 conjugates (Fig. 22b, c) with water solubility of
27.5 mg/mL and 3.5 mg/mL, respectively. Interestingly, the authors evaluated the
ability of a bis-αCD-C 60 conjugate to inhibit hepatitis C virus (HCV) in Huh7 cell
lines. This revealed significant anti-HCV activity (half-maximal inhibitory concentration (IC 50 ) 0.17 μM) (Fig. 22d), which was strongly dose dependent [98]. They
also evaluated the anti-influenza A/WSN/33 (H1N1) virus activity of bis-γCD-C 60
conjugates in MDCK cell lines and found that they displayed distinct activity. The
IC 50 values of conjugates B and C were 87.73 Æ 6.9 μM and 75.06 Æ 5.1 μM,
respectively, while that of oseltamivir (Tamiflu), which was used as a control, was
33.6 Æ 2.2 μM [99].
14.4 Conclusions
The special geometric structure of cyclodextrins (CDs) and their three different kinds
of hydroxyl groups express different chemical properties, which provide excellent
potential reactive sites for further modification to fulfill numerous applications.
Since scientists first demonstrated the structure of CDs, they have never stopped
exploring their applications and methods of functionalization. Sometimes, because
they want to achieve specific goals, they look for and discover appropriate functionalization method(s); sometimes they research particular methodologies based on new
functionalization methods and discover new applications. At the early stages,
functionalization of CDs was random; then, as scientists discovered more chemical
properties of CDs (for example, the three different kinds of hydroxyl groups express
different chemical properties; the hydroxyl groups on the primary rim possess less
steric hindrance than those on the secondary rim), chemists started to develop
selective functionalization strategies. Tert-butyldimethylsilyl chloride (TBDMSCl)
is the most common reagent chosen to synthesize primary-rim-modified cyclodextrins
because under optimal conditions it can give a 90% yield of the desired products
[100]. Site-specific selective functionalization of CDs is a more challenging aim to
accomplish. Since certain methods such as aluminum–alkane reagent–mediated
deprotection of per-protected CDs were discovered [13a], the process of site-selective
functionalization of CDs has been accelerated.
With their hydrophilic surface and hydrophobic inner cavity, CDs are perceived
as ideal molecules for developing delivery systems, such as nanoparticle and multivalence delivery systems, that can be used in delivering molecules for medical
diagnosis, biosensing, gene therapy, or chemotherapy. Ideas from scientists have
14 Functionalized Cyclodextrins and Their Applications in Biodelivery
419
poor water solubility. To overcome this disadvantage, Zhang and coworkers
designed and synthesized a bis-αCD-C 60 conjugate (Fig. 22a) using αCDs as
carriers, after a selective deprotection reaction on the second rim to give monolCD, followed by a coupling reaction to produce a CD dimer, which, via
Bingel–Hirsch cyclopropanation, provided the bis-αCD-C 60 conjugate. This
functionalized strategy tremendously enhanced the water solubility of C 60 from
1.3 Â 10
À11 to 0.5 mg/mL. On the basis of a similar concept, they also synthesized
two other species of bis-γCD-C 60 conjugates (Fig. 22b, c) with water solubility of
27.5 mg/mL and 3.5 mg/mL, respectively. Interestingly, the authors evaluated the
ability of a bis-αCD-C 60 conjugate to inhibit hepatitis C virus (HCV) in Huh7 cell
lines. This revealed significant anti-HCV activity (half-maximal inhibitory concentration (IC 50 ) 0.17 μM) (Fig. 22d), which was strongly dose dependent [98]. They
also evaluated the anti-influenza A/WSN/33 (H1N1) virus activity of bis-γCD-C 60
conjugates in MDCK cell lines and found that they displayed distinct activity. The
IC 50 values of conjugates B and C were 87.73 Æ 6.9 μM and 75.06 Æ 5.1 μM,
respectively, while that of oseltamivir (Tamiflu), which was used as a control, was
33.6 Æ 2.2 μM [99].
14.4 Conclusions
The special geometric structure of cyclodextrins (CDs) and their three different kinds
of hydroxyl groups express different chemical properties, which provide excellent
potential reactive sites for further modification to fulfill numerous applications.
Since scientists first demonstrated the structure of CDs, they have never stopped
exploring their applications and methods of functionalization. Sometimes, because
they want to achieve specific goals, they look for and discover appropriate functionalization method(s); sometimes they research particular methodologies based on new
functionalization methods and discover new applications. At the early stages,
functionalization of CDs was random; then, as scientists discovered more chemical
properties of CDs (for example, the three different kinds of hydroxyl groups express
different chemical properties; the hydroxyl groups on the primary rim possess less
steric hindrance than those on the secondary rim), chemists started to develop
selective functionalization strategies. Tert-butyldimethylsilyl chloride (TBDMSCl)
is the most common reagent chosen to synthesize primary-rim-modified cyclodextrins
because under optimal conditions it can give a 90% yield of the desired products
[100]. Site-specific selective functionalization of CDs is a more challenging aim to
accomplish. Since certain methods such as aluminum–alkane reagent–mediated
deprotection of per-protected CDs were discovered [13a], the process of site-selective
functionalization of CDs has been accelerated.
With their hydrophilic surface and hydrophobic inner cavity, CDs are perceived
as ideal molecules for developing delivery systems, such as nanoparticle and multivalence delivery systems, that can be used in delivering molecules for medical
diagnosis, biosensing, gene therapy, or chemotherapy. Ideas from scientists have
14 Functionalized Cyclodextrins and Their Applications in Biodelivery
419