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 CH2Cl2 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) (PEG13-TEMPO), alkyne-terminated poly(ε-caprolactone) (PCL28-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.