Quadruple click reactions for the synthesis of cysteine-functional heterograft brush copolymer

The quadruple click reactions, thiol-ene, copper catalyzed azide-alkyne cycloaddition (CuAAC), Diels-Alder cycloaddition, and nitroxide radical coupling (NRC) reactions were successfully employed for the synthesis of cysteine-functional heterograft brush copolymer. An equimolar mixture of oxanorbornenyl-anthracene (ONB-anthracene), oxanorbornenyl-bromide (ONB-Br), and oxanorbornenyl tosylate (ONB-OTs) was polymerized via ring opening metathesis polymerization (ROMP) using the first generation Grubbs' catalyst in CH ₂Cl₂ at room temperature to form poly(ONB-anthracene-co- ONB-Br-co-ONB-OTs)₁₀ copolymer as a main backbone. Next, this main backbone was first reacted with N-acetyl-L-cysteine methyl-ester via radical thiol-ene click reaction and then sequentially clicked with a furan protected maleimide-terminated poly(methyl methacrylate) (PMMA₂₀-MI), and 2,2,6,6-tetramethyl-1-piperidinyloxy-terminated poly(ethylene glycol) (PEG ₁₃-TEMPO), alkyne-terminated poly(ε-caprolactone) (PCL ₂₈-alkyne) via Diels-Alder, and NRC/CuAAC reactions, respectively to yield a cysteine-functional poly(ONB-g-PMMA-co-ONB-g-PEG-co-ONB-g-PCL) ₁₀ heterograft brush copolymer.