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

Elizabeth Ladd; Amir Sheikhi; Na Li; Theo G M van de Ven; Ashok Kakkar

doi:10.3390/molecules22060868

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

Molecules. 2017 May 24;22(6):868. doi: 10.3390/molecules22060868.

Authors

Elizabeth Ladd^{1

2

3}, Amir Sheikhi^{4

5

6}, Na Li^{7

8}, Theo G M van de Ven^{9

10

11}, Ashok Kakkar^{12

13}

Affiliations

¹ Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada. elizabeth.ladd@mail.mcgill.ca.
² Pulp and Paper Research Centre, McGill University, 3420 rue University, Montreal, QC H3A 2A7, Canada. elizabeth.ladd@mail.mcgill.ca.
³ Centre for Self-Assembled Chemical Structures, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada. elizabeth.ladd@mail.mcgill.ca.
⁴ Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada. amir.sheikhi@mail.mcgill.ca.
⁵ Pulp and Paper Research Centre, McGill University, 3420 rue University, Montreal, QC H3A 2A7, Canada. amir.sheikhi@mail.mcgill.ca.
⁶ Centre for Self-Assembled Chemical Structures, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada. amir.sheikhi@mail.mcgill.ca.
⁷ Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada. Blinan04st@gmail.com.
⁸ Centre for Self-Assembled Chemical Structures, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada. Blinan04st@gmail.com.
⁹ Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada. theo.vandeven@mcgill.ca.
¹⁰ Pulp and Paper Research Centre, McGill University, 3420 rue University, Montreal, QC H3A 2A7, Canada. theo.vandeven@mcgill.ca.
¹¹ Centre for Self-Assembled Chemical Structures, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada. theo.vandeven@mcgill.ca.
¹² Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada. ashok.kakkar@mcgill.ca.
¹³ Centre for Self-Assembled Chemical Structures, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada. ashok.kakkar@mcgill.ca.

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.

Keywords: bactericide; click chemistry; dendrimers; hyperbranched macromolecules; synthesis.

MeSH terms

Anti-Bacterial Agents / chemistry
Click Chemistry / methods*
Dendrimers / chemistry*
Molecular Structure

Substances

Anti-Bacterial Agents
Dendrimers