Slightly congested amino terminal dendrimers. The synthesis of amide-based stable structures on a large scale

Abstract

Nowadays, amino terminal dendrimers are appealing materials for biological applications due to their multivalence and the versatile conjugation of the amino groups. However, the high reactivity of these terminal groups can be decreased by steric hindrance, limiting their possible bioapplications. Herein, we report the divergent synthesis of slightly sterically hindered amino terminal polyamide dendrimers. A simple and unique AB₂ scaffold has been chosen to build the dendritic structures, where only amide bonds have been used as the connecting unit. The 1–7 relative positions of the amino groups in the AB₂ monomers avoid the steric congestion of the macromolecules, allowing the construction of robust dendrimers up to the fifth generation. The construction of the dendrimers is based on two well-established reactions, using simple and cheap reactants, with yields above 90% on a gram scale and easy purification procedures. This synthetic methodology constitutes an easy and efficient way for the preparation of stable and aqueous soluble dendrimers on a gram scale, representing a substantial improvement over the synthesis of this kind of aliphatic polyamide amino terminal dendrimer. The prepared structures were completely characterized and evaluated by size exclusion chromatography, diffusion ordered spectroscopy and atomic force microscopy to determine their size. Molecular dynamics simulations were also carried out and the values obtained were consistent with the experimentally determined values.