Synthesis and facile end-group quantification of functionalized PEG azides

Abstract

Azido-functionalized poly(ethylene glycol) (PEG) derivatives are finding ever-increasing applications in the areas of conjugation chemistry and targeted drug delivery by their judicious incorporation into nanoparticle-forming polymeric systems. Quantification of azide incorporation into such PEG polymers is essential to their effective use. ¹H Nuclear Magnetic Resonance (NMR) analysis offers the simplest approach; however, the relevant adjacent azide-bearing methylene protons are often obscured by the PEG manifold signals. This study describes the synthesis of 1,2,3-triazole adducts from their corresponding PEG azides via a convenient, mild click reaction, which facilitates straightforward NMR-based quantitative end-group analysis.This method was found to be compatible with many examples of bifunctional azido PEGs with molecular weights ranging from 2 to 18 kDa bearing a variety of functional groups. © 2016 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 2888-2895.

Keywords: NMR spectroscopy; azides; calculations; click chemistry; hydrophilic polymers; poly(ethylene glycol); triazoles; water‐soluble polymers.

Scheme 1

Triazole forming click reaction.

Scheme 2

Syntheses of azido PEG derivatives.

Figure 1

¹H NMR (CD₃CN) of mPEG3.5K‐N₃.

Figure 2

¹H NMR (CD₃CN, 400 MHz) of DEBD click adduct.