Milan M. Stamenović

Additive-Free Clicking for Polymer Functionalization and Coupling by Tetrazine–Norbornene Chemistry

Herein we report the use of a tetrazine-norbornene inverse electron demand Diels-Alder conjugation applied to polymer end-functionalization and polymer-polymer coupling. The reaction was found to be applicable to polymer-polymer coupling, as judged by SEC, DOSY NMR, and LCxSEC analyses, giving diblock copolymers by merely mixing the constituent homopolymers together under ambient conditions, using no catalyst, additive, or external stimulus.

Straightforward synthesis of functionalized cyclic polymers in high yield via RAFT and thiolactone–disulfide chemistry

An efficient synthetic pathway toward cyclic polymers based on the combination of thiolactone and disulfide chemistry has been developed. First, heterotelechelic linear polystyrene (PS) containing an α-thiolactone (TLa) and an ω-dithiobenzoate group was synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization, employing a newly designed TLa-bearing chain transfer agent (CTA). The subsequent reaction of this heterotelechelic polymer with an amine, which acts as a nucleophile for both the TLa and dithiobenzoate units, generated the α,ω-thiol-telechelic PS under ambient conditions without the need for any catalyst or other additives. The arrangement of thiols under a high dilution afforded single cyclic PS (c-PS) through an oxidative disulfide linkage. The cyclic PS (c-PS) disulfide ring formation was evidenced by SEC, MALDI-TOF MS and 1H-NMR characterization. Moreover, we demonstrated a controlled ring opening via either disulfide reduction or thiol–disulfide exchange to enable easy and clean topology transformation. Furthermore, to illustrate the broad utility of this synthetic methodology, different amines including functional ones were employed, allowing for the one-step preparation of functionalized cyclic polymers with high yields.

Double modular modification of thiolactone-containing polymers: towards polythiols and derived structures

A conceptual proof for the double modification (aminolysis and subsequent thiol-click modification) of thiolactone units, incorporated in linear polymer scaffolds, was elaborated. These polymers were prepared by either reversible addition–fragmentation chain transfer (RAFT) or nitroxide mediated radical polymerization (NMP) starting from a stable, readily available styrenic thiolactone monomer (St-TLa). Successful copolymerization of the latter with styrene (St) or methyl methacrylate (MMA) yielded linear polymers with varying thiolactone content (4–25%). Upon amine treatment, the ring-opening of the pendent thiolactones resulted in the formation of linear polythiols. Reaction conditions were optimized to avoid cross-linking via disulfide formation, thus preserving the linear nature of the polymer. Different primary amines (propylamine, benzylamine, ethanolamine and Jeffamine M-1000) were attached to the polymer backbone, while the PDIs remained low. The resulting polythiols are versatile scaffolds for further modification by various thiol-click reactions. In this respect, thiol–maleimide conjugation was used as a model reaction. NMR- and SEC-analyses revealed a near-quantitative double modification of thiolactone containing polystyrene (PS) and poly(methylmethacrylate) (PMMA) by subsequent treatment with propylamine and N-benzylmaleimide.

Synthesis of multi-functionalized hydrogels by a thiolactone-based synthetic protocol

We established a simplified synthetic protocol for the preparation of multiple functionalized hydrogels, which is potentially employable for the fabrication of adaptable sensors, using the recently introduced thiolactone chemistry. Thiolactone groups can be opened with a primary amine, through which a functional group is introduced, while at the same time a thiol is released, which is available for crosslinking or further functionalization. In this respect, a thiolactone functionalized poly(N-isopropylacryl amide) (p(NIPAAm-co-TlaAm)) precursor, obtained via RAFT, and 3-morpholinopropylamine or histamine as the ring opening amines are used to synthesize gels responding to CO2. The synthetic protocol relies on a newly discovered crosslinking mechanism involving the solvent dichloromethane as the crosslinking agent. We discuss the gel formation protocol in detail, including the crosslinking mechanism, and additionally demonstrate the response of the synthesized gels towards CO2. Finally, we show how the applied synthetic protocol can be used for the preparation of multiple functionalized gels, extending the concept to optical response type gels.

From NMP to RAFT and Thiol-Ene Chemistry by In Situ Functionalization of Nitroxide Chain Ends

A straightforward, novel strategy based on the in situ functionalization of polymers prepared by nitroxide-mediated polymerization (NMP), for the use as an extension toward block copolymers and post-polymerization modifications, has been investigated. The nitroxide end group is exchanged for a thiocarbonylthio end group by a rapid transfer reaction with bis(thiobenzoyl) disulfide to generate in situ reversible addition-fragmentation chain transfer (RAFT) macroinitiators. Moreover, not only have these macroinitiators been used in chain extension and block copolymerization experiments by the RAFT process but also a thiol-terminated polymer is synthesized by aminolysis of the RAFT end group and subsequently reacted with dodecyl vinyl ether by thiol-ene chemistry.