High-yield Path to Dendrimers

A copper(I)-catalyzed fusion reaction of azides and alkynes to form 1,2,3-triazoles has been applied to dendrimer synthesis for the first time and has been found to give dendrimer yields higher than those achieved with any other reactions.

Dendrimers are large, globular molecules comprising several branches--or dendrons--emanating from a central core. A range of functional groups can be put on dendrimer surfaces to endow them with specific chemical and physical properties.

Applications of dendrimers ranging from drug delivery to smart materials have been suggested. In practice, however, dendrimer development has been slowed by the difficulty of making them in significant quantities. Although akin to polymers in molecular weight, dendrimers are prepared by stepwise syntheses, which typically give low yields.

The copper-catalyzed chemistry leading to triazoles, developed earlier by chemists Valery V. Fokin and K. Barry Sharpless at Scripps Research Institute, now appears to offer a simple, reliable, and productive dendrimer synthesis method. Each dendron is made up of 1,2,3-triazole repeating units formed by the almost perfectly efficient reaction between the azide and acetylene starting materials. The reaction is repeated the requisite number of times to achieve the dendron size desired. The same chemistry may also be used to attach the dendrons to a central core and to introduce functional groups at the periphery.

With chemist Craig J. Hawker at IBM Almaden Research Center, San Jose, Calif., and others, Fokin and Sharpless used the reaction to prepare and characterize dendrimers of high surface diversity in high purity and in higher yields than have been achieved before [Angew. Chem. Int. Ed., published online June 30, http://www3.interscience.wiley.com/cgi-<br > bin/abstract/109086281]. The reaction is so robust that it "works great in pure Jack Daniels," according to Hawker. Fokin notes that the reaction can indeed be carried out in a wide range of different solvents.

The route "is clearly a breakthrough in dendrimer synthesis," says Donald A. Tomalia, director of the National Center for Dendrimer-Based Nanotechnology at Central Michigan University, Mount Pleasant, and president and chief technology officer of Dendritic Nanotechnologies.

The method "shows enormous power," given the number of repetitions required to synthesize high-molecular-weight dendrimers, adds E. W. (Bert) Meijer, a professor of macromolecular and organic chemistry at Eindhoven University of Technology, in the Netherlands.

Because the reaction is atom-economical and proceeds practically to completion, no by-products are formed and purification often requires nothing more than filtration.

The first rounds of reaction "work beautifully, with quantitative yields and no copper contamination," Fokin says. With the fourth round, cleanup may require more than just filtration, but yields are still close to 90%. Previously, a 10% yield of a dendron had been considered good, he adds.