Zwitterionic Moieties from the Huisgen Reaction: A Case Study with Amphiphilic Dendritic Assemblies

Abstract

Supramolecular nano-assemblies that reduce non-specific interactions with biological macromolecules, such as proteins, are of great importance for various biological applications. Recently, zwitterionic materials have been shown to reduce non-specific interactions with biomolecules, owing both to their charge neutrality and their ability to form strong hydration layer around zwitterions via electrostatic interactions. In this article, we present new triazole-based zwitterionic moieties that are incorporated as the hydrophilic functionalities in facially amphiphilic dendrons. The amphiphilic zwitterionic dendrons spontaneously self-assemble in aqueous solutions forming micelle-type aggregates, which are confirmed by DLS, TEM, and fluorescence techniques. We also compare the structural and functional characteristics of the zwitterionic dendrons with the corresponding charge-neutral PEG-based dendrons and anionic carboxylate-based dendrons. Surface charge measurements, temperature sensitivity and evaluation of interactions of these assemblies with proteins form the bases for these comparisons.

Antibiofouling polymer interfaces: poly(ethylene glycol) and other promising candidates

“…108 Zwitterionic polymers have also been successful at conferring protein resistant properties to nanoparticles. 20,109 To this end, zwitterionic polymers have been used in a variety of nanoparticulate systems, including surface coatings for gold nanoparticles [110][111][112] and nanorods, 113 silica nanoparticles, 114 iron oxide nanoparticles, 115,116 block copolymer micelles, 117 knedel-like polymers, 118 dendrimers, 119 polymeric immunobeads, 120,121 and quantum dots 122,123 and in protein conjugates. 124 In these applications, zwitterionic particles can strongly resist protein fouling.…”

Structures and Synthesis of Zwitterionic Polymers

“…As the cleavage of such an ester function often has the character of the deprotection step in protecting group chemistry, especially if tert-butyl esters are employed [93,94,349,357,[398][399][400][401][402], it generally provides excellent yields. Thus, chances are very high to obtain rather clean polyzwitterions if not the amine, but the quaternized ammonium derivative is already engaged as monomer in the polymerization.…”

“…Of course, the Huisgen 1,3-dipolar cycloaddition can be also employed in less direct approaches. For instance, zwitterionic dendrimers were made by clicking -azido-tert-butylacetate to polymer bound alkyne groups, followed by methylation of the triazole formed and subsequent hydrolysis of the tert-butylester to yield triazoliocarboxylate moieties [400].…”

Protein-Triggered Supramolecular Disassembly: Insights Based on Variations in Ligand Location in Amphiphilic Dendrons

“…Also, we have shown how controlled variations in PEG density could affect interactions of nanoparticles with proteins. Developing zwitterionic moieties, 35 which have the potential to circumvent the steric hindrance exhibited by lengthy PEG chains in amphiphilic systems, for use in protein-binding-induced disassembly is part of the ongoing focus in our laboratories.…”