Straightforward synthesis of cysteine-reactive telechelic polystyrene

Synthesis of a thiol-reactive telechelic polystyrene and conjugation of cysteine is reported. A dimethylfulvene-protected maleimide-functionalized atom transfer radical polymerization (ATRP) initiator (3) was synthesized, and the thermostability was compared to the analogous furan-protected initiator (1) by thermogravometric analysis (TGA). The former protecting group was stable to a higher temperature than the latter in the bulk phase (143°C vs 125°C) and thus was investigated as an initiator for the ATRP of styrene. Kinetic studies of the polymerization of styrene mediated by copper(I)/N,N,N′, N″,N″-pentamethyldiethylenetriamine (PMDETA) indicated that the reaction proceeded in a controlled manner with high initiator efficiency (92%). Polystyrene with a number-average molecular weight (M_n) of 2530 Da and a narrow polydispersity index (PDI) of 1.15 was then synthesized and subjected to atom transfer radical (ATR) coupling to form the bis-functionalized polymer. Gel permeation chromatography (GPC) and ¹H NMR spectroscopy studies indicated that dimerization had occurred and that the end groups were intact. Reactivity of the polymer was demonstrated by an in-situ retro-Diels-Alder and thioether bond formation first with model compound benzyl mercaptan and then with the amino acid N-acetyl-L-cysteine methyl ester. Bis-conjugation was verified by inspection of the ¹H NMR spectra and by elemental analysis.