Journal of the American Chemical Society 2011-01-26

Core-clickable PEG-branch-azide bivalent-bottle-brush polymers by ROMP: grafting-through and clicking-to.

Jeremiah A Johnson, Ying Y Lu, Alan O Burts, Yeon-Hee Lim, M G Finn, Jeffrey T Koberstein, Nicholas J Turro, David A Tirrell, Robert H Grubbs

Index: J. Am. Chem. Soc. 133 , 559-566, (2011)

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Abstract

The combination of highly efficient polymerizations with modular "click" coupling reactions has enabled the synthesis of a wide variety of novel nanoscopic structures. Here we demonstrate the facile synthesis of a new class of clickable, branched nanostructures, polyethylene glycol (PEG)-branch-azide bivalent-brush polymers, facilitated by "graft-through" ring-opening metathesis polymerization of a branched norbornene-PEG-chloride macromonomer followed by halide-azide exchange. The resulting bivalent-brush polymers possess azide groups at the core near a polynorbornene backbone with PEG chains extended into solution; the structure resembles a unimolecular micelle. We demonstrate copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click-to" coupling of a photocleavable doxorubicin (DOX)-alkyne derivative to the azide core. The CuAAC coupling was quantitative across a wide range of nanoscopic sizes (∼6-∼50 nm); UV photolysis of the resulting DOX-loaded materials yielded free DOX that was therapeutically effective against human cancer cells.