Design and Synthesis of Dendrimers with Facile Surface Group Functionalization, and an Evaluation of Their Bactericidal Efficacy

Abstract

We report a versatile divergent methodology to construct dendrimers from a tetrafunctional core, utilizing the robust copper(I) catalyzed alkyne-azide cycloaddition (CuAAC, “click”) reaction for both dendrimer synthesis and post-synthesis functionalization. Dendrimers of generations 1–3 with 8–32 protected or free OH and acetylene surface groups, were synthesized using building blocks that included acetylene- or azide-terminated molecules with carboxylic acid or diol end groups, respectively. The acetylene surface groups were subsequently used to covalently link cationic amino groups. A preliminary evaluation indicated that the generation one dendrimer with terminal NH3+ groups was the most effective bactericide, and it was more potent than several previously studied dendrimers. Our results suggest that size, functional end groups and hydrophilicity are important parameters to consider in designing efficient antimicrobial dendrimers.

From Nanobiotechnology, Positively Charged Biomimetic Dendrimers as Novel Antibacterial Agents: A Review

“…By using the robust copper (I) catalyzed alkyne-azide cycloaddition (CuAAC) “click reaction” for dendrimer synthesis and for post-synthesis functionalization, Ladd et al reported a versatile divergent methodology to construct ammonium-terminated Ds from the tetrafunctional core pentaerythritol [ 99 ]. Ds of generations 0–3 (G0–G3) were achieved with from 4 to 32 acetylene surface groups, which in G0–G2 Ds were subsequently used to covalently link cationic amino groups.…”

Telodendrimer-Based Macromolecular Drug Design using 1,3-Dipolar Cycloaddition for Applications in Biology

“…We first explored the potential of 1,3-dipolar cycloaddition strategy in the synthesis of a symmetric generation 0 dendrimer. It was begun by the propargylation of pentaerythritol using propargyl bromide with potassium hydroxide in dry DMF (Scheme 1) [32], followed by the 1,3dipolar cycloaddition on the tetrapropargylated core (3) using a bromonitrile oxide precursor (4) in THF at 45 °C for 3 h, with NaHCO3 as base and ZnCl2 as a catalyst. It afforded 5,5′-(((2,2-bis(((3bromoisoxazol-5-yl)methoxy)methyl)propane-1,3-diyl)bis(oxy))bis(methylene))bis(3bromoisoxazole) (5) in 44% isolated yield (Scheme 1) [33].…”

Prospects of Nanostructure Materials and Their Composites as Antimicrobial Agents

“…Not only this, dendrimer itself can act as a powerful microbicide by using the antimicrobial agent as an elementary unit and the plausible mode of microbial toxicity is accredited to the polycationic structural feature which facilitates its adsorption onto the negatively charged bacterial cell. Once adsorbed, increased membrane permeability is witnessed that ensures entry of more dendrimers inside the cell which later facilitate K + ions leakage and complete loss of bacterial membrane integrity (Chen and Cooper, 2002 ; Ladd et al, 2017 ). The detailed discussion on antimicrobial activity of dendrimers has been described elsewhere (Scorciapino et al, 2017 ).…”