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

Abstract

Abstract 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 2 Cl 2 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) (PMMA 20 -MI), and 2,2,6,6-tetramethyl-1-piperidinyloxy-terminated poly(ethylene glycol) (PEG 13 -TEMPO), alkyne-terminated poly(e-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.