Published on Web 09/22/2009
Facile Synthesis of Polyester Dendrimers from Sequential
Click Coupling of Asymmetrical Monomers
Xinpeng Ma,† Jianbin Tang,‡ Youqing Shen,*,‡,† Maohong Fan,† Huadong Tang,†
and Maciej Radosz†
Center for Bionanoengineering and State Key Laboratory of Chemical Engineering, Department
of Chemical and Biological Engineering, Zhejiang UniVersity, Hangzhou, China 310027, and
Department of Chemical and Petroleum Engineering, UniVersity of Wyoming,
Laramie, Wyoming 82071
Received May 7, 2009; E-mail: shenyq@zju.edu.cn; sheny@uwyo.edu
Abstract: Polyester dendrimers are attractive for in vivo delivery of bioactive molecules due to their
biodegradability, but their synthesis generally requires multistep reactions with intensive purifications. A
highly efficient approach to the synthesis of dendrimers by simply “sticking” generation by generation together
is achieved by combining kinetic or mechanistic chemoselectivity with click reactions between the monomers.
In each generation, the targeted molecules are the major reaction product as detected by matrix-assisted
laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The only separation needed
is to remove the little unreacted monomer by simple precipitation or washing. This simple clicklike process
without complicated purification is particularly suitable for the synthesis of custom-made polyester
dendrimers.
Introduction
ecules for exclusion from the body. However, to make these
dendrimers useful in practice, researchers must develop more
Dendrimers, the highly branched macromolecules character-
ized by precise three-dimensional nanosized molecular struc-
tures, provide a perfect nanotechnology platform for numerous
applications,1,2 particularly in pharmaceutics as drug and gene
carriers3-5 because of their internal cavity for drug encapsula-
tion,6 large numbers of surface functional groups for drug
conjugations, and unusually low intrinsic viscosity in solution7
for easy transport in blood. While many types of dendrimers
such as polyamidoamine- (PAMAM-) based dendrimers have
been reported as carriers, polyester dendrimers are most
attractive4,5,8 because of their biodegradability, which allows
the macromolecules to degrade or hydrolyze into small mol-
efficient synthesis approaches.
Polyester dendrimers, like other dendrimers, are generally
synthesized via the divergent5,9-12 and convergent12,13 ap-
proaches. Both approaches involve repeated reactions between
functional groups A and B in multifunctional monomers Ax and
By or ABx. When the Ax and By types of monomers are used, a
large excess of the reactant must be used in each step to
minimize cross-linking.9 Consequently, a large quantity of
unreacted monomer must be removed to isolate the dendrimer.
When an ABx-type monomer is used, the B groups are generally
protected to make the A group react solely with the B groups
in the prior generation of dendrimer. Deprotection is needed to
reactivate the B groups for the subsequent reaction.14 This
protection and deprotection may be incomplete and may have
† University of Wyoming.
‡ Zhejiang University.
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