An investigation of the copolymerization of EO and PO by in situ1H NMR spectroscopy reveals striking differences in the monomer gradient, depending on the polymerization method.

The statistical copolymerization of isoprene with p-ethyl- (p-ES), p-isopropyl- (p-iPS), and p-tert-butylstyrene (p-tBS) initiated by sec-butyllithium in cyclohexane was investigated with respect to kinetics, reactivity ratios, and formation of tapered block copolymers with pronounced monomer gradient. An efficient synthetic route to the monomers was developed on a multigram scale, relying on the precipitation of the side-product triphenylphosphine oxide at low temperature. The copolymerization kinetics and resulting molecular weight distributions were analyzed. The dispersity, Đ, of the copolymers depends on the p-alkyl substituent, the the degree of polymerization P n and the comonomer mole fraction, X. In situ 1H NMR kinetics characterization revealed a strong gradient structure for all three copolymer systems (r I = 21.9, r p‑ES = 0.022; r I = 19.7, r p‑iPS = 0.027; r I = 19.8, r p‑tBS = 0.022). The rate of crossover from a polyisoprenyl­lithium chain end (I) to a p-alkylstyrene (S) unit relative to the alkylstyrene homopolymerization, k IS/k SS (in 10–3 (L mol–1)−1/4), decreases in the order p-MS (19.1) > p-ES (11.3) > p-iPS (5.71) ≈ p-tBS (5.63), supporting the observed, increasingly bimodal character of the molecular weight distributions and the higher dispersity. Thermogravimetric analysis revealed that all poly­(p-alkylstyrene) homopolymers are stable up to 300 °C.

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.

The tailormade ester functional epoxides, methyl 4,5epoxypentenoate (MEP) and t butyl 4,5-epoxypentenoate ( t BEP), were synthesized in good overall yields (60−65%) in short reaction sequences. Both MEP and t BEP were investigated as comonomers in the statistical copolymerization with ethylene oxide (EO) via the monomer-activated anionic ring-opening polymerization (MAROP), using triisobutyl-aluminum as a catalyst. Homopolymers and a series of copolymers of EO with varied molar contents of MEP and t BEP (0.6−31.3 mol %) were prepared, possessing molecular weights up to 11,800 g mol −1 . Surprisingly, in situ 1 H NMR kinetics studies revealed an ideally random copolymer microstructure for EO/MEP copolymers (r EO = 0.99, r MEP = 1.0) via MAROP for the first time. t BEP was found to be a less reactive comonomer, yielding gradient polyether structures (r EO = 2.9, r t BEP = 0.35). After polymerization, the ester-protecting groups were fully cleaved under basic or acidic conditions, respectively, resulting in either random or gradient distribution of carboxyl moieties. MTT assays demonstrated good biocompatibility of the novel carboxylic acid functional poly(ethylene glycol) (PEG) copolymers. The thermal properties of the copolymers were investigated via differential scanning calorimetry, showing the highly flexible nature of the PEG-based polyelectrolytes after deprotection. The liberated carboxylic acid groups were addressed with Ca 2+ cations, resulting in cross-linked polymer networks.