Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials.

Atsushi Tamura,Nobuhiko Yui,Yoshinori Arisaka,Asato Tonegawa

doi:10.3762/bjoc.12.287

Atsushi Tamura, Nobuhiko Yui + Show 2 more

Open Access

https://doi.org/10.3762/bjoc.12.287

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Abstract

Cyclodextrin (CD)-threaded polyrotaxanes (PRXs) with reactive functional groups at the terminals of the axle polymers are attractive candidates for the design of supramolecular materials. Herein, we describe a novel and simple synthetic method for end-reactive PRXs using bis(2-amino-3-phenylpropyl) poly(ethylene glycol) (PEG-Ph-NH2) as an axle polymer and commercially available 4-substituted benzoic acids as capping reagents. The terminal 2-amino-3-phenylpropyl groups of PEG-Ph-NH2 block the dethreading of the α-CDs after capping with 4-substituted benzoic acids. By this method, two series of azide group-terminated polyrotaxanes (benzylazide: PRX-Bn-N3, phenylazide: PRX-Ph-N3,) were synthesized for functionalization via click reactions. The PRX-Bn-N3 and PRX-Ph-N3 reacted quickly and efficiently with p-(tert-butyl)phenylacetylene via copper-catalyzed click reactions. Additionally, the terminal azide groups of the PRX-Bn-N3 could be modified with dibenzylcyclooctyne (DBCO)-conjugated fluorescent molecules via a copper-free click reaction; this fluorescently labeled PRX was utilized for intracellular fluorescence imaging. The method of synthesizing end-reactive PRXs described herein is simple and versatile for the design of diverse functional PRXs and can be applied to the fabrication of PRX-based supramolecular biomaterials.

Highlights

Polyrotaxanes (PRXs) are a class of interlocked polymers that consist of an inclusion complex of cyclodextrins (CDs) and a linear axle polymer capped with bulky stopper molecules [1,2,3]
To investigate whether PRXs could be obtained via 4-substituted benzoic acids, the end capping reaction of commonly utilized pseudopolyrotaxanes comprising bis(aminopropyl) PEG (PEG-NH2) (1) and α-CD was performed using 4-azidobenzoic acid as a model compound (Scheme 1A)
The synthesis of PRXs was assessed with size exclusion chromatography (SEC) measurements in dimethyl sulfoxide (DMSO), in which the unreacted pseudopolyrotaxanes were readily dissociated into their constituent compounds

Summary

Introduction

Polyrotaxanes (PRXs) are a class of interlocked polymers that consist of an inclusion complex of cyclodextrins (CDs) and a linear axle polymer capped with bulky stopper molecules [1,2,3]. The synthesis and characterization of PRXs bearing azide groups and their reactivity against model alkynes via copper-catalyzed click reactions are performed. 2a is insufficient bulky to prevent the dethreading of CDs from PRXs. To achieve the synthesis of end-reactive polyrotaxanes using 4-substituted benzoic acids as capping reagents, it is necessary to increase the bulkiness of the terminal group of the axle polymer.

Results

Conclusion