2024 Volume 7 Issues 1–3

Open Access

INEOS OPEN, 2024, 7 (1–3), 3–4  Journal of Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences Download PDF Electronic supplementary information DOI: 10.32931/io2402a

Synthesis of Carbosilane Dendrimers with an Amine-Containing Shell Using CuAAC

Abstract

A new synthetic approach to carbosilane dendrimers bearing amino-containing functional groups in the shell is proposed based on the Cu-catalyzed azide–alkyne cycloaddition. The structures of the resulting compounds are confirmed using ¹H, ¹³C, and ²⁹Si NMR spectroscopy, as well as gel permeation chromatography.

Key words: carbosilane dendrimers, click reaction, azide–alkyne cycloaddition, N,N-dimethylpropargylamine, 2-ethynylpyridine.

 

Introduction

Dendrimers with an amine shell are widely used for the delivery of biologically active molecules and DNA and for the creation of dendriplexes and various nanostructures [1–3].

In turn, carbosilane dendrimers feature high chemical stability, inertness and hydrophobicity of the framework, while maintaining high reactivity of the functional groups and offering proper analytical control during the structure formation up to high generations [4, 5].

The hydrophobic internal framework of carbosilane dendrimers in combination with the amine shell opens up new ways of using carbosilane dendrimers for the delivery of drugs and genes, as well as for the coordination of metal ions [6].

Results and discussion

In this work, a series of new carbosilane dendrimers with two types of the amine-containing functional shells, namely, dimethylamine (G1-NMe₂ and G2-NMe₂) and pyridin-2-yl (G1-C₅H₄N and G2-C₅H₄N) were synthesized. The dendrimers were obtained by the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction between the previously obtained first and second generation carbosilane dendrimers with an azidopropyl shell (G1-N₃, G2-N₃) [7] and N,N-dimethylpropargylamine or 2-ethynylpyridine (Scheme 1).

Scheme 1. Synthesis of G2-NMe₂ and G2-C₅H₄N.

A combination of heterocyclic 1,2,3-triazole rings with the conjugated pyridine and dimethylamine chelating units enables the application of such structures for the coordination of transition metal ions, for example, for the stabilization of narrowly dispersed silver nanoparticles [8]. That is why 2-ethynylpyridine and 1,1-dimethylpropargylamine were chosen for the functionalization of the carbosilane dendrimers featuring an azide shell.

CuAAC was carried out in dry THF at 60 °C upon addition of 1 mol % of CuI. The reaction course was monitored using ¹H NMR spectroscopy by the disappearance of the signals of characteristic CH₂ groups at the azide moiety and the appearance of new ones, corresponding to the completion of CuAAC (Fig. 1). The structures of the compounds obtained were confirmed by ¹H, ¹³C, ²⁹Si NMR spectroscopy for all the compounds and gel permeation chromatography (GPC) for G1-C₅H₄N and G2-C₅H₄N (see Figs. S1–S18 in the Electronic supplementary information (ESI)).

Figure 1. ¹H NMR spectra of G2-N₃, G2-NMe₂, and G2-C₅H₄N.

Experimental section

General remarks

The synthesis of the first and second generation carbosilane dendrimers with an azidopropyl shell was described earlier [7]. THF was dried by the standard procedure. 2-Ethynylpyridine, N,N-dimethylpropargylamine (98%, Sigma Aldrich), and CuI (Acros Organics) were purchased from commercial sources and used without further purification.

The ¹H, ¹³C, ²⁹Si spectra were recorded with a Bruker Avance 300 NMR spectrometer in CDCl₃; chemical shifts were referenced relative to residual chloroform signal (7.26 ppm, ¹H).

The GPC analysis was performed on a Shimadzu chromatograph (Japan, Germany) using a RID-20A refractometer detector, Phenogel 5u 1000 Å column (300 × 7.8 mm), polystyrene standards, and THF as an eluent. The experiments were performed at 40 °C with the flow rate of 1 mL/s.

Syntheses

General procedure. A mixture of the azide-terminated dendrimer, the acetylene substrate, 1 mol % of CuI, and the catalytic amount of Et₃N in THF was stirred at 60 °C for 6 h. The conversion was monitored using ¹H NMR spectroscopy. The product was evacuated at 60 °C and 0.5 mbar.

The detailed synthetic procedure for each dendrimer is presented in the ESI.

Conclusions

The first and second generation carbosilane dendrimers with the dimethylaminotriazole shell and carbosilane dendrimers with the triazole–pyridine shell were synthesized using the CuAAC reaction. The developed approach can be further used to obtain carbosilane dendrimers with a cationic shell for biomedical applications or for coordination of metal ions.

Acknowledgements

This work was supported by the Russian Science Foundation, project no. 22-13-00459. The molecular-weight distribution and NMR spectroscopic studies were performed with financial support from the Ministry of Science and Higher Education of the Russian Federation (№ FFSM-2021-0004) using the equipment of the Collaborative Access Center "Center for Polymer Research" of ISPM RAS and within the framework of the program of state support for the centers of the National Technology Initiative (NTI) on the basis of educational institutions of higher education and scientific organizations (Сenter NTI "Digital Materials Science: New Materials and Substances" on the basis of the Bauman Moscow State Technical University).

Electronic supplementary information

Electronic supplementary information (ESI) available online: the synthetic procedures for the dendrimers; the ¹H, ¹³C, and ²⁹Si spectra; the GPC curves. For ESI, see DOI: 10.32931/io2402a.

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