Thiol-terminated four-armed poly(ethylene glycol) PEG4SH was prepared in a manner similar to Goessl et al.,(6 (link)) but with some significant modifications. Five grams of hydroxy-terminated, four-armed PEG (MW 10 000) (Jenkem) was dissolved in 70 mL of toluene in a round-bottomed flask and refluxed at 80 °C. Sodium hydride (Sigma-Aldrich), 1.5 mol equiv with respect to hydroxyls, was added to the solution. Allyl bromide (Sigma-Aldrich), 1.5 mol equiv relative to hydroxyls, was diluted with 10 mL of toluene and added dropwise to the solution via an addition funnel. The reaction was refluxed overnight at 80 °C.
Any unreacted sodium hydride was neutralized with the addition of 1 mL of methanol, whereupon sodium salts were removed via filtration, and the PEG was recovered from solution by precipitation in cold diethyl ether. The PEG tetraallyl ether was dried in vacuo and then redissolved in 50 mL of methanol in a 100 mL round-bottom flask, to which was added 0.10 g of the radical photoinitiator 2,2-dimethoxy-1,2-diphenylethan-1-one (trade name Irgacure 651, BASF). Thiol acetic acid (Sigma-Aldrich), 1.5 equiv relative to the allyl groups, was added, and the solution was stirred vigorously under exposure to 10 mW/cm2 365 nm UV light for 20 min. PEG thioacetate was recovered from solution by precipitation and dried as before. Dried PEG thioacetate was dissolved in 20 mL of deionized water (diH2O), whereupon 20 mL of 2 M NaOH was added and the solution was stirred for 5 min, and 11 mL of 4 N HCl solution was added to acidify the solution and discourage disulfide formation. The aqueous solution was extracted with equivalent volumes of chloroform twice, combined fractions were concentrated by rotary evaporation, and product was recovered by precipitation in cold diethyl ether. Substitution was determined to be ∼90% by both Ellman’s analysis and proton NMR. The initiator LAP was synthesized as described previously.(20 (link))
Any unreacted sodium hydride was neutralized with the addition of 1 mL of methanol, whereupon sodium salts were removed via filtration, and the PEG was recovered from solution by precipitation in cold diethyl ether. The PEG tetraallyl ether was dried in vacuo and then redissolved in 50 mL of methanol in a 100 mL round-bottom flask, to which was added 0.10 g of the radical photoinitiator 2,2-dimethoxy-1,2-diphenylethan-1-one (trade name Irgacure 651, BASF). Thiol acetic acid (Sigma-Aldrich), 1.5 equiv relative to the allyl groups, was added, and the solution was stirred vigorously under exposure to 10 mW/cm2 365 nm UV light for 20 min. PEG thioacetate was recovered from solution by precipitation and dried as before. Dried PEG thioacetate was dissolved in 20 mL of deionized water (diH2O), whereupon 20 mL of 2 M NaOH was added and the solution was stirred for 5 min, and 11 mL of 4 N HCl solution was added to acidify the solution and discourage disulfide formation. The aqueous solution was extracted with equivalent volumes of chloroform twice, combined fractions were concentrated by rotary evaporation, and product was recovered by precipitation in cold diethyl ether. Substitution was determined to be ∼90% by both Ellman’s analysis and proton NMR. The initiator LAP was synthesized as described previously.(20 (link))
