Synthesis of Amino Terminal Clicked Dendrimers. Approaches to the Application as a Biomarker

Abstract

Herein, we present an easy and efficient synthesis of amino terminal dendrons, combining protection/ deprotection reactions with copper-catalyzed azide alkyne cycloaddition in a convergent way. This new approach affords dendrons in gram scale with excellent yields and easy purification. By choosing the appropriate azido-functionalized core, these dendrons lead to a more efficient and controlled convergent synthesis of dendrimers with different sizes and shapes and multivalence. The amino terminal dendrimers were analyzed by diffusion-ordered spectroscopy experiments. The observed dendrimer size is in excellent correlation with the expected size and shape by molecular dynamic simulations. The construction of these kinds of nanostructures, in a simple and efficient way, opens new opportunities for biomedical applications. Moreover, by choosing the appropriate core, these versatile macromolecules become an excellent fluorescent biomarker.

Slightly congested amino terminal dendrimers. The synthesis of amide-based stable structures on a large scale

“…In order to achieve a higher separation between amine terminal groups, 5-amino-2-(3-aminopropyl)pentanoic acid was selected as a platform to build the dendrimers. This will arrange the terminal amino groups in a 1,7 relative position, achieving less steric hindrance than in previously prepared BAPAD 21 or clicked dendrimers, 23 where the amino groups were in a 1,3 relative position. The presence of a carboxylic acid and two amino groups in the selected AB 2 monomer will ensure that all connections will be exclusively amide bonds.…”

“…However, as previously reported, characterization of dendrimers with high molecular weights and charges by MALDI-TOF is extremely difficult. 23,37,38 For G4-5 no MALDI spectrum could be obtained, probably due to the high lability of the Boc protecting groups (in Gx-NHBoc) and the high degree of positive charges (in G4-5) during measurements.…”

“…Different dendrimers were also prepared using cores of different multiplicities, demonstrating the potential of this methodology for the assembly of dendrimers with a controlled shape and number of amino terminal groups. 23 These amide-based dendritic structures are completely stable, aqueous soluble and versatile enough to be used in different bioapplications. Thus, dendrons based on this structure were used as platforms in diagnosis tests of allergic reactions to drugs.…”

Thiol-Ene Click Inspired Late-Stage Modification of Long-Chain Polyurethane Dendrimers

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] After Tomalia's first report on poly(amidoamine) (PAMAM) dendrimers in 1985, 20 many research groups have reported the synthesis dendritic macromolecules using ether, ester, carbosilane, amide, and alkyne linkages. [21][22][23][24][25][26][27][28][29][30][31][32][33] Nevertheless, very few have reported the synthesis of dendrimers having urethane linkage. It is noteworthy that, as of now, SciFinder ® reveals less than 100 references showing the entry of polyurethane dendrimers, which is negligible as compared to the references reported on polyurethane polymers (more than 340,000).…”

Thiol-Ene Click Inspired Late-Stage Modification of Long-Chain Polyurethane Dendrimers

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] After Tomalia's first report on poly(amidoamine) (PAMAM) dendrimers in 1985, 20 many research groups have reported the synthesis dendritic macromolecules using ether, ester, carbosilane, amide, and alkyne linkages. [21][22][23][24][25][26][27][28][29][30][31][32][33] Nevertheless, very few have reported the synthesis of dendrimers having urethane linkage. It is noteworthy that, as of now, SciFinder ® reveals less than 100 references showing the entry of polyurethane dendrimers, which is negligible as compared to the references reported on polyurethane polymers (more than 340,000).…”