Synthesis of Thiolated Four-Arm PEG

The synthesis of thiolated four-arm PEG was performed as previously reported.^{38 (link)} In short, PEG (1meq.), MP (40meq.), and PTSA (0.4meq.) were dissolved in toluene. Under a flow of nitrogen, the reaction was refluxed with stirring for 48hrs (Scheme 1). Water was collected by using a Dean-Stark trap. Toluene was removed under reduced pressure and the polymer was precipitated 3 times in cold ether. The polymer was reduced by dissolving 1meq in methylenechloride with DTT (1meq) and triethylamine (1meq) under nitrogen for 5hrs. The reaction was acidified with trifluoroacetic acid (1.1meq) and precipitated in ether and rinsed with copious amounts of 2-propanol and hexane. Functionality was determined via ¹H NMR spectroscopy and was approximately four (>95%). ¹H NMR (CDCl₃): δ = 4.28 (8H, CH₂-O-C(O), m), 3.74-3.50 (900H (CH₂-CH₂-O)_n, bs), 2.84-2.64 (16H, CH₂-CH₂-SH, m) (Figure S1).