Poly(ethylene glycol) with Multiple Aldehyde Functionalities Opens up a Rich and Versatile Post-Polymerization Chemistry

Two novel epoxide monomers 3,3-dimethoxy-propanyl glycidyl ether (DMPGE) and 3,3-dimethoxy-2,2-dimethylpropanyl glycidyl ether (DDPGE) were developed for the introduction of multiple aldehyde functionalities into the poly­(ethylene glycol) (PEG) backbone. The acetal protecting group for the aldehyde functionality is stable against the harsh, basic conditions of the anionic ring-opening polymerization. Both monomers could be homopolymerized as well as copolymerized randomly with ethylene oxide (EO) in a controlled fashion. Copolymers with molecular weights (M_n) in the range of 4500–20100 g/mol and low dispersity (M_w/M_n) between 1.06 and 1.14 were obtained. The polymers were characterized by size exclusion chromatography, ¹H NMR spectroscopy, and by differential scanning calorimetry regarding their thermal properties. The controlled character of the copolymerization was verified by MALDI-TOF. To study the distribution of the acetal-protected aldehyde functionalities at the polyether chains, the copolymerization with EO was monitored by in situ ¹H NMR kinetics experiments for both monomers. These measurements revealed almost ideally random distribution of the comonomers with reactivity ratio pairs r_EO = 0.96, r_DMPGE = 1.04 and r_EO = 1.20, r_DDPGE = 0.83. The acetal functionalities of DMPGE polymers were successfully addressed by hydrazone formation. In addition, DDPGE copolymers were successfully deprotected in acidic media, and various transformations yielded aldehyde-, ester-, and nitrile-functionalized PEG while maintaining a dispersity below 1.1. Consequently, these monomers represent promising building blocks for the synthesis of multifunctional PEG for a variety of biomedical purposes.