Chemistry Reference
In-Depth Information
SCHEME 11.1
Representative structures of commonly used cyclodextrins.
development in recent years, many nanomedicine and drug delivery designs incor-
porated CDs as major structural elements, capitalizing on their unique dendrite-like
functionalities and the hosting capability of the annular cavity [4]. To explore its
vast spectrum of applications, it is critically important to recognize that CDs have
to be modified chemically to achieve their desirable functions. In this chapter, we
will discuss how “click” reactions [5], a new chemistry tool, would potentiate the
biomedical applications of the CDs.
11.2 CHEMICAL MODIFICATION OF CYCLODEXTRINS
Most biomedical applications of CDs involve the chemical conjugations of CD struc-
tures to other functional structure elements. Due to the availability of the multiple
hydroxyl groups on the rims of CDs, most of the chemical modifications of these
functional groups are therefore the first step in derivatization of CD. According to
their different
pKa
values and nucleophilicity, primary or secondary hydroxyl groups
can be selectively modified. Under neutral, acidic, and weak basic conditions, the
primary hydroxyl groups have relatively higher nucleophilic substitution potential
than secondary hydroxyl groups. While under strong basic conditions, nucleophilic
substitution mainly takes place on secondary hydroxyl groups. No selectivity can be
achieved among the primary hydroxyl groups on the narrow rim or among secondary
hydroxyl groups on the wide rim in the process of chemical modification because of
their structural similarity. However, monosubstituted CDs can be obtained by con-
trolling the conversion ratio and applying different purification methodologies. For
example, treatment of
-CD with p-toluenesulfonic anhydride under basic aqueous
conditions would lead to monotosylation of the primary hydroxyl group on
-CD
[6]. Derived from these intermediates, other functionalities such as halide and azide
can be introduced. Interestingly, it is possible to obtain disubstituted CDs by using
bifunctional reagents with geometry matching the distance between two primary
hydroxyl groups on the narrow rim. Similarly, selective multisubstitution of CDs can
also be achieved. Therefore, in theory, by controlling the pH value of the reaction
media, the amount and geometry of the reagents, a variety of substituted CDs with
defined structure can be prepared [7].
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