Design, Synthesis, and Characterization of Fully Zwitterionic, Functionalized Dendrimers.

Abstract

Dendrimers are interesting candidates for various applications because of the high level of control over their architecture, the presence of internal cavities, and the possibility for multivalent interactions. More specifically, zwitterionic dendrimers modified with an equal number of oppositely charged groups have found use in in vivo biomedical applications. However, the design and control over the synthesis of these dendrimers remains challenging, in particular with respect to achieving full modification of the dendrimer. In this work, we show the design and subsequent synthesis of dendrimers that are highly charged while having zero net charge, that is zwitterionic dendrimers that are potential candidates for biomedical applications. First, we designed and fully optimized the synthesis of charge-neutral carboxybetaine and sulfobetaine zwitterionic dendrimers. Following their synthesis, the various zwitterionic dendrimers were extensively characterized. In this study, we also report for the first time the use of X-ray photoelectron spectroscopy as an easy-to-use and quantitative tool for the compositional analysis of this type of macromolecules that can complement techniques such as nuclear magnetic resonance and gel permeation chromatography. Finally, we designed and synthesized zwitterionic dendrimers that contain a variable number of alkyne and azide groups that allow straightforward (bio)functionalization via click chemistry.