Selectively functionalized glycerol/diacid dendrimers via click chemistry of azido fatty acids

Authors: Zerkowski, Jonathan; Nunez, Alberto; Solaiman, Daniel

Submitted to: Journal of the American Oil Chemists' Society
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/7/2010
Publication Date: 3/1/2011
Citation: Zerkowski, J.A., Nunez, A., Solaiman, D. 2011. Selectively functionalized glycerol/diacid dendrimers via click chemistry of azido fatty acids. Journal of the American Oil Chemists' Society. 88(3):403-413.

Interpretive Summary: Using glycerol and fatty acids, which are biorenewable compounds from agricultural sources, we have prepared several new representatives of the class of molecules known as dendrimers, whose name derives from their highly branched “tree-like” structure. Molecules with this shape have received intense study due to their ability to surround or hide other small guest molecules, which can become entangled within the crevices of the branches. This property has led dendrimers to be used as drug-delivery or controlled-release agents, since the drug can becarried into a biological system and then leak out slowly over time. Our approach to preparing these molecules relies on a stepwise, rather than an all-at-once method, where the branches of the product are built up one bond at a time. In this way, a desired chemical building block can be inserted into the final dendrimer at a selected position, and in a known ratio. This selectivity is an advance over previous techniques for dendrimer synthesis; it can be used to append special reactive groups that might direct the dendrimer (and any encapsulated guest molecules) to specific sites in a cell, or the reactive groups can be used to hold onto the guest with greater specificity.

Technical Abstract: Abstract: Dendrimers consisting of glycerol and dicarboxylic acid units were synthesized using a convergent or “outside-in” strategy. The multimeric arms, or dendrons, are joined to a central core in the final step using the azide/alkyne click reaction. The combination of these approaches allows the preparation of dendrimers with variable, and controlled, degrees of substitution at their periphery. For example, a single protected amino acid has been situated at the periphery, with all other substituents being hydrophobic. In another example, all the peripheral substituents are protected amino acids. The identity of the dendrimers is unambiguous due to the purification and characterization of all synthetic intermediates. Functional groups have also been selectively incorporated along the arms (dicarboxylic acids) and at the cores.