In the rapidly evolving multidisciplinary field of polymer therapeutics, tailored polymer structures represent the key constituent to explore and harvest the potential of bioactive macromolecular hybrid structures. In light of the recent developments for anticancer drug conjugates, multifunctional polymers are becoming ever more relevant as drug carriers. However, the potentially best suited polymer, poly(ethylene glycol) (PEG), is unfavorable owing to its limited functionality. Therefore, multifunctional linear copolymers (mf-PEGs) based on ethylene oxide (EO) and appropriate epoxide comonomers are attracting increased attention. Precisely engineered via living anionic polymerization and defined with state-of-the-art characterization techniques-for example real-time (1)H NMR spectroscopy monitoring of the EO polymerization kinetics-this emerging class of polymers embodies a powerful platform for bio- and drug conjugation.

Introduction of highly reactive vinyl ether moieties along a poly(ethylene glycol) (PEG) backbone has been realized by copolymerization of the novel epoxide monomer ethoxy vinyl glycidyl ether (EVGE) with ethylene oxide (EO). A series of copolymers with varying structure (block and random) as well as EVGE comonomer content (5À100%) with molecular weights in the range of 3,900À13,200 g/mol and narrow molecular weight distributions (M w /M n = 1.06À1.20) has been synthesized and characterized with respect to their microstructure and thermal properties. The facile transformation of the vinyl ether side chains in click type reactions was verified by two different post polymerization modification reactions: (i) thiolÀene addition and (ii) acetal formation, employing various model compounds. Both strategies are very efficient, resulting in quantitative conversion. The rapid and complete acetal formation with alcohols results in an acid-labile bond and is thus highly interesting with respect to biomedical applications that require slow or controlled release of a drug, while the thiolÀene addition to a vinyl ether prevents cross-linking efficiently compared to other double bonds.

No abstract

A series of poly(ethylene glycol-co-isopropylidene glyceryl glycidyl ether) (P(EO-co-IGG)) random copolymers with different fractions of 1,2-isopropylidene glyceryl glycidyl ether (IGG) units was synthesized. After acidic hydrolysis a new type of "functional PEGs", namely poly(ethylene glycolco-glyceryl glycerol) (P(EO-co-GG)) was obtained. Using an initiator that releases a terminal amino moiety after deprotection, functional end groups with orthogonal reactivity to the in-chain groups were obtained. All polymers showed narrow molecular weight distributions (1.07-1.19), and control of the molecular weights was achieved in the range 5000-30 000 g/mol. Random incorporation of both comonomers was verified by monitoring the copolymerization kinetics via real-time 1 H NMR spectroscopy during the polymerization and by characterization of the triad sequence distribution, relying on 13 C NMR analysis. Using the 1,2-diol component of the side chains allows for attachment and facile acid-catalyzed release of molecules bearing ketone/aldehyde functionalities. This renders the materials potentially useful as support for reagents, drugs or catalysts. This was demonstrated using benzaldehyde as a model compound. DSC was carried out on all samples, showing amorphous structures upon incorporation of IGG fractions exceeding 15%.

Hetero-multifunctional poly(ethylene glycol-co-glycerol) random copolymers with multiple hydroxyl functionalities and a single terminal functionality have been prepared by copolymerization of ethylene oxide (EO) and ethoxy ethyl glycidyl ether (EEGE) with the use of a suitable initiator, introducing a protected amino group or a double bond, respectively. Acidic deprotection was used for removal of the acetal protecting groups in the chain, and the terminal amino group was regenerated by catalytic hydrogenation. A series of copolymers with narrow polydispersity was obtained, varying comonomer fractions from 3 to 67% and molecular weights in the range of 5 000-32 000 g · mol(-1) (1.05 < $\overline M _{\rm w} /\overline M _{\rm n}$ < 1.25). Molecular and thermal characterization was carried out using (1) H- and (13) C NMR, SEC and differential scanning calorimetry (DSC).