A Convergent Approach to Biocompatible Polyglycerol “Click” Dendrons for the Synthesis of Modular Core–Shell Architectures and Their Transport Behavior

Abstract

Dendrimers are an important class of polymeric materials for a broad range of applications in which monodispersity and multivalency are of interest. Here we report on a highly efficient synthetic route towards bifunctional polyglycerol dendrons on a multigram scale. Commercially available triglycerol (1), which is highly biocompatible, was used as starting material. By applying Williamson ether synthesis followed by an ozonolysis/reduction procedure, glycerol-based dendrons up to the fourth generation were prepared. The obtained products have a reactive core, which was further functionalized to the corresponding monoazido derivatives. By applying copper(I)-catalyzed 1,3-dipolar cycloaddition, so-called "click" coupling, a library of core-shell architectures was prepared. After removal of the 1,2-diol protecting groups, water-soluble core-shell architectures 24-27 of different generations were obtained in high yields. In the structure-transport relationship with Nile red we observe a clear dependence on core size and generation of the polyglycerol dendrons.

Dendritic Polyglycerols for Biomedical Applications

“…The focal point of the PG dendrons were then functionalized to azido groups by mesylation of the secondary hydroxyl group followed by subsequent reaction with sodium azide. [103] For synthesizing modular core/shell architectures the azide terminated, acetal protected PG dendrons can be ''clicked'' onto diverse oligoacetylene cores. Upon removal of the acetal protection groups, amphiphilic compounds can be obtained in high yields ranging from 92% for [G.2] to 67% for [G.4] dendrons (Fig.…”

“…[100,103] The synthetic protocol included the linking of the dendrons through amidation or click coupling. These architectures were evaluated as solubilizing agents for the hydrophobic dye Nile red.…”

Multivalent Peptide–Nanoparticle Conjugates for Influenza‐Virus Inhibition

“…To identify the optimal scaffold for a multivalent inhibitor, we chose dendritic PGs with different molecular weights and degrees of azide functionalization for peptide conjugation. CuAAC was carried out in basic ammonium bicarbonate buffer at room temperature overnight and the reaction mixture was pre‐purified by dialysis, followed by size exclusion chromatography 36. The conjugation products were analyzed by NMR spectroscopy and DLS to obtain the size and number of ligands for each peptide–polymer conjugate (Table 1 and Supporting Information).…”

Dendronized core-multishell nanocarriers for solubilization of guest molecules

“…The reaction was cooled to 0 °C in a water-icebath. Then 1-ethyl-3- to literature procedures [31,32]. dPG amine (M n 10,000 g/mol)…”