CuAAC Reaction Synthesis Strategy for Dendrimers

Copper-assisted azide-alkyne cycloaddition (CuAAC) is a widely used click chemistry reaction not only for the synthesis of dendrimers but also for functionalized dendrimers. With advanced technology and experienced scientists, CD BioSciences offers you CuAAC synthesis services for dendrimers.

Click Chemistry and CuAAC

As an efficient and reliable method of chemical synthesis, click chemistry has made a great contribution to chemical synthesis by its simplicity of operation and water resistance, and can be used to construct various substances with complex molecular structures for synthesis. Click chemistry can be applied to many fields such as drug development and biomedical materials and has become one of the most useful and attractive chemical synthesis methods. There are many chemical synthesis methods based on click chemistry, such as CuAAC reaction, thiol-ene and thiol-yene click (TEC/TYC) reactions and Diels-Alder (DA) reactions, among others. In terms of simplicity, scope of application, solvent, and substrate insensitivity, CuAAC is the only widely used universal click reaction so far. In addition to the seven orders of magnitude increase in reaction rate, CuAAC leads to the feasibility of reactions in organic solvents, water, or ionic solutions, thus driving CuAAC to be completed within minutes at room temperature.

Typical conditions for the CuAAC reaction, a 1,3-dipolar cycloaddition, and the resulting product. (Pasini D, 2013)

Mechanism of CuAAC

CuAAC is a Huisgen1,3-dipolar cyclization reaction in which 1,4-disubstituted [1,2,3]-triazoles are formed between a terminal alkyl group and an aliphatic azide in the presence of copper, and the beneficial outcome of copper(I) catalysis of the thermal Huisgen reaction is attributed to an overcoming the kinetic barrier in the formation of the desired triazole ring. This is manifested by the initial formation of a π-complex of copper(I) and an alkyl substrate (I), which lowers the pkA value of the acetylate to 9.8, thus facilitating the formation of copper(I)-acetylate (II). In the next step, the formation of the dinuclear/triplex complex (III) with the coordinated azide group leads to a preorientation of the reactive functional groups, which in turn leads to the formation of a six-membered ring through the nucleophilic attack of the azide, introducing the first covalent CN bond (IV). The desired 1,2,3-triazole product (V) is provided by the cationization of the second CN bond, which, upon final addition of the electrophile, gives rise to the exclusive 1,4-regioisomer (VI).

Mechanistic details of the CuAAC as currently proposed. (Neumann S, et al., 2019)

CuAAC Reaction Synthesis for Dendrimers

As the most important and widely used click reaction, CuAAC can be applied in medicinal chemistry and other chemistries and is a common tool for building complex molecular structures. Due to its high efficiency, it has been widely used in the fields of bio coupling, polymer, and dendrimer synthesis. When CuAAC is applied to the field of dendrimers, it can be used not only for the synthesis of dendrimers but also for functionalized dendrimers (including conjugation with small molecules).

Our Services

CD BioSciences offers click chemistry-based dendrimer CuAAC synthesis services and guarantee that all deliverables undergo rigorous quality testing to ensure quality and reliability and are delivered on time.

What We Provide

Service Process

As a leading global provider of custom services, CD BioSciences has advanced facilities and experienced scientists to synthesize a variety of dendrimers through click chemistry synthesis methods such as CuAAC, TEC/TYC reactions, DA reactions, and other click chemistry-based methods to help our customers advance their downstream applications of dendrimers. If you are interested in our services or have any other questions, please feel free to contact us, we would be happy to hear from you and look forward to working with you.

References

1. Pasini D. The click reaction as an efficient tool for the construction of macrocyclic structures. Molecules. 2013, 18: 9512-30.
2. Neumann S.; et al. The CuAAC: Principles, Homogeneous and Heterogeneous Catalysts, and Novel Developments and Applications. Macromol Rapid Commun. 2020, 41:1-32.