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 (<i>M</i><sub>n</sub>) in the range of 4500–20100 g/mol and low dispersity (<i>M</i><sub>w</sub>/<i>M</i><sub>n</sub>) between 1.06 and 1.14 were obtained. The polymers were characterized by size exclusion chromatography, <sup>1</sup>H 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 <i>in situ</i> <sup>1</sup>H NMR kinetics experiments for both monomers. These measurements revealed almost ideally random distribution of the comonomers with reactivity ratio pairs <i>r</i><sub>EO</sub> = 0.96, <i>r</i><sub>DMPGE</sub> = 1.04 and <i>r</i><sub>EO</sub> = 1.20, <i>r</i><sub>DDPGE</sub> = 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.