Chemistry Reference
In-Depth Information
Most CD functionalizations, however, are not single-step substitutions, but involve
multiple steps of derivatization. To get the objective products, strict reaction condi-
tions have to be met. Temperature, solvent, water, oxygen, reaction time, and reagent
ratios are the most common concerns. Therefore, CD modifications often give poor
yield and selectivity. Furthermore, the competing reaction sites and spatial hindrance
usually would lead to structure uncertainty and decrease in reaction efficiency. Due
to these limitations of the conventional methodologies, the field has been constantly
in need of more efficient tools for CDs' derivatization with better functional group
tolerance and mild reaction condition requirements [7].
Originally conceptualized by Sharpless et al. [5], “click” chemistry encompasses
a group of reactions that are modular, high yielding, stereospecific, and generate
inoffensive byproducts. The main characteristics of “click” reactions include simple
reaction conditions, readily available starting materials and reagents, the use of no
solvent or a solvent that is benign or easily removed, and simple product isolation
[5]. Among the identified “click” reactions, Cu(I)-catalyzed azide-alkyne cycload-
dition, namely the Huisgen 1,3-dipolar cycloaddition (HDC) reaction, is the most
widely reported. With azides and terminal alkynes as starting materials, this reaction
exclusively forms 1,4-substituted products. The reaction can be carried out within
a wide temperature range (0
◦
C -160
◦
C), in a variety of solvent systems (including
water), and over a wide range of pH values (5-12). It proceeds as much as 10
7
times
faster than the uncatalyzed version. Furthermore, it is unaffected by steric factors [8].
Different primary, secondary, tertiary, and aromatic azides readily participate in this
reaction. It also has excellent tolerance for various acetylene reactants [9].
Clearly, these unique features of the Cu(I)-catalyzed HDC reaction make it
a powerful tool in organic coupling reactions. For the complex CD derivatiza-
tion/conjugation, which have often been plagued by rigorous reaction conditions,
multiple reaction sites and spatial hindrance, these exceptional features of HDC
reactions were especially valuable.
11.3 BIOMEDICAL APPLICATIONS
Since “click” reactions were first introduced to the modification of CDs, a large num-
ber of CD derivatives have been rationally designed and prepared. In the following
sections, some recent representative developments using novel “click”-modified CDs
are discussed in detail, focusing on their biomedical applications in the area of chiral
separation, functional biomaterials, biosensors, and drug delivery.
11.3.1 Chiral Separation
Chirality of active pharmaceutical ingredients (APIs) is essential for their biologi-
cal activities. Different enantiomers or diastereomers may have significantly differ-
ent, or even completely reversed activities [10]. Therefore, effective detection and
separation of chiral isomers are of great importance for the pharmaceutical indus-
try. Chromatography techniques, especially high-performance liquid chromatography
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