“Click” methodologies: efficient, simple and greener routes to design dendrimers

Abstract

Designing dendrimers that are monodisperse hyperbranched macromolecules and offer significant potential in numerous scientific fields, is becoming a major topical area in modern research. Among the challenges of the 21st century, synthetic methodologies that increase efficiency of conversion and a greener chemistry approach, are expected to lead the way in the quest to build novel nanomaterials. The recent entry of so-called "click" reactions that include Diels-Alder, Cu(I)-catalyzed Huisgen cycloaddition and thiol-ene coupling, have generated real stimulus not only in developing elegant materials of choice, but also in making the leap to industrial scale build-up of dendritic macromolecules. This tutorial review takes on the task of demonstrating the simplicity of these "click" reactions and the advantages they offer from a synthetic view point in developing mono- to multifunctional dendrimers. A brief introduction to "click" chemistry is followed by a chronological survey of developments in the field, and the impact these have had in designing novel dendritic macromolecules. The review is intended to introduce scientists to these highly efficient methodologies with demonstrated potential, and provide impetus for further growth of the area.

Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model

“…In gene delivery, most studies have used the limited number of commercial dendrimers for further chemical modification (27)(28)(29). However, orthogonal click chemistry has recently made a transformative impact on the synthesis of dendritic materials through protecting group-free methodologies to overcome historical limitations in fidelity and provide a larger toolbox for dendrimer design (30)(31)(32)(33)(34). The expansion of dendrimer applications therefore depends on the ability to easily tune the size, chemistry, topology, and, ultimately, dendrimer physical properties through chemical synthesis.…”

Dendrimer-based magnetic resonance imaging agents for brain cancer

“…It is worth noting that "click" chemistry has been successfully implemented in dendrimer synthesis, offering simplified and accelerated synthesis, and at the same time, diverse structural complexity [49,50]. "Click" reactions give a high yield within a short reaction time, yet can be performed under mild conditions and with high atom economy.…”

Glycodendritic structures: tools to interact with DC-SIGN

“…The click chemistry reaction CuAAC is a very efficient, versatile, and popular reaction that has found several applications in many fields to achieve the preparation of very diverse molecules ranging from small compounds to polymers, hydrogel and other larges entities, including dendrimers (Wu et al, 2004;Joralemon et al, 2005;Malkoch et al, 2005;Fernández-Megia et al, 2006;Franc, Kakkar, 2010). Following a convergent strategy based on CuAAC reaction, the synthesis of a new class of glycodendrons with full control of the structure was developed.…”