title: Oxidation-Responsive and "Clickable" Poly(ethylene glycol) via Copolymerization of 2-(Methylthio)ethyl Glycidyl Ether.
abstract: Poly(ethylene glycol) (PEG) is a widely used biocompatible polymer. We describe a novel epoxide monomer with methyl-thioether moiety, 2-(methylthio)ethyl glycidyl ether (MTEGE), which enables the synthesis of well-defined thioether-functional poly(ethylene glycol). Random and block mPEG-b-PMTEGE copolymers (Mw/Mn = 1.05-1.17) were obtained via anionic ring opening polymerization (AROP) with molecular weights ranging from 5 600 to 12 000 g·mol(-1). The statistical copolymerization of MTEGE with ethylene oxide results in a random microstructure (rEO = 0.92 ± 0.02 and rMTEG E = 1.06 ± 0.02), which was confirmed by in situ (1)H NMR kinetic studies. The random copolymers are thermoresponsive in aqueous solution, with a wide range of tunable transition temperatures of 88 to 28 °C. In contrast, mPEG-b-PMTEGE block copolymers formed well-defined micelles (Rh ≈ 9-15 nm) in water, studied by detailed light scattering (DLS and SLS). Intriguingly, the thioether moieties of MTEGE can be selectively oxidized into sulfoxide units, leading to full disassembly of the micelles, as confirmed by detection of pure unimers (DLS and SLS). Oxidation-responsive release of encapsulated Nile Red demonstrates the potential of these micelles as redox-responsive nanocarriers. MTT assays showed only minor effects of the thioethers and their oxidized derivatives on the cellular metabolism of WEHI-164 and HEK-293T cell lines (1-1000 μg·mL(-1)). Further, sulfonium PEG polyelectrolytes can be obtained via alkylation or alkoxylation of MTEGE, providing access to a large variety of functional groups at the charged sulfur atom.
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.|Graduate School Materials Science in Mainz , Staudinger Weg 9, 55128 Mainz, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Herzberger
authors.affiliation: Institute of Physical Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.|Graduate School Materials Science in Mainz , Staudinger Weg 9, 55128 Mainz, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Leibig
authors.affiliation: Department of Dermatology, University Medical Center of the Johannes Gutenberg-University , Langenbeckstrasse 1, 55131 Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bros
authors.affiliation: Fraunhofer ICT-IMM , Carl-Zeiss-Str.18-20, 55129 Mainz, Germany.
authors.forename: Raphael
authors.initials: R
authors.lastname: Thiermann
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.|Graduate School Materials Science in Mainz , Staudinger Weg 9, 55128 Mainz, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Frey