Versatile, Highly Controlled Synthesis of Hybrid (Meth)acrylate–Polyester–Carbonates and their Exploitation in Tandem Post‐Polymerization–Functionalization

Abstract

The use of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) as a mild catalyst for the ring‐opening polymerization (ROP) of the pharma‐friendly and biodegradable monomer lactide and a functionalizable tert‐butyloxycarbonyl (BOC)‐protected cyclic carbonate is explored. Successful and controlled ROP is demonstrated when employing a series of labile‐ester (bis)(meth)acrylate initiators to produce macromonomers suitable for a range of post‐polymerization modifications. Importantly, the use of DBU ensured retention of the BOC group of the carbonate monomer during the polymerization, thus facilitating the production of highly functionalizable hybrid materials unobtainable using the more reactive triazabicyclodecene (TBD). Subsequently, a variety of short homo‐ and copolymers are synthesized with good control over material properties and final polymer composition. Successful attainment of these short copolymers confirm that DBU can overcome the previously observed limitations of TBD related to its kinetic competition between ROP and transesterification side‐reactions under these reaction conditions. Furthermore, the fidelity of the hydroxyl and (meth)acrylic end groups are maintained as confirmed by a series of secondary tandem reactions. The macromonomers are also utilized in reversible addition−fragmentation chain‐transfer polymerization (RAFT) polymerization for the production of amphiphilic block or random copolymers with a hydrophilic comonomer, poly(ethyleneglycol)methacrylate. The amphiphilic copolymers produced via the tandem RAFT reaction demonstrate the ability to self‐assemble into monodisperse nanoparticles in aqueous environments.

2‐Methyltetrahydrofuran (2‐MeTHF) as a versatile green solvent for the synthesis of amphiphilic copolymers via ROP, FRP, and RAFT tandem polymerizations

“…To corroborate the versatility of 2‐MeTHF and the ability of DBU to control polymerization reactions at 65°C, rather than at room temperature as explored in the previous literature, [ 19 ] HEMA (Figure S4 as integrated spectra example) and PEGMA‐initiated LA macromonomers were synthesized targeting a final DP n of 25 (DP n calculated from spectra integration as for Figure S4 and ref. [19]). The control at such temperature would allow both total monomer and initiators solubility as well as the possibility to conduct radical polymerizations, AIBN initiated, in tandem simply in 2‐MeTHF.…”

“…[30][31][32] In previous work, our group has assessed that the mild activity of DBU would prevent such transesterification side-reactions, even when targeting a DP n below 35 was found to be unachievable with TBD. [19,30] This would allow for tandem polymerization, allowing for the production of polymers with a greater range of architectures and chemistries. To corroborate the versatility of 2-MeTHF and the ability of DBU to control polymerization reactions at 65 C, rather than at room temperature as explored in the previous literature, [19] HEMA ( Figure S4 as integrated spectra example) and PEGMA-initiated LA macromonomers were synthesized targeting a final DP n of 25 (DP n calculated from spectra integration as for Figure S4 and ref.…”

“…[18] The production of versatile biodegradable copolymers with hybrid architectures can be achieved by employing functional initiators such as (meth)acrylates, which introduce an end-chain reactive double bond to the final polymer product. [19] The functionality of the resultant copolymers can be explored further with a second synthesis step, such as free radical polymerization (FRP) or a controlled mechanism as reversible addition-fragmentation chain-transfer (RAFT) polymerization. [11] Previously we demonstrated the suitability of 2-MeTHF for ROP process producing a library of PDLLAbased oligomers initiated by terpene-alcohols, achieving a totally sustainable chemical process.…”

Antimicrobial Hyperbranched Polymer–Usnic Acid Complexes through a Combined ROP‐RAFT Strategy

“…[15,16] Previously, we have demonstrated a facile and highlyaccessible route to a range of amphiphilic polymeric materials through a combined ring-opening polymerization (ROP) and reversible addition−fragmentation chain-transfer (RAFT) polymerization strategy. [17,18] Particularly, we have shown that the use of 2-hydroxyethyl methacrylate (HEMA) as a bifunctional initiator for the ROP step gives ready access to biodegradable macromonomers that can be polymerized into interesting final architectures, such as hyperbranched polymers (HBs). [19] HBs show great promise for drug delivery applications on account of their unimolecular nature (no critical aggregation concentration), small particle sizes (less than 50 nm), and their highly branched structure, which provides a high local density of functional groups for further functionalization with drugs.…”

A ‘greener’ one-pot synthesis of monoterpene-functionalised lactide oligomers

“…The catalyst is 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU), a naturally occurring, non-nucleophilic amidine base [30][31][32] which has mild activity to minimise side reactions and preserve key functionalities both on the headgroups, backbone and end-group moieties. [30,37] A key target is to demonstrate the crucial importance of the retention of the "terpenoid double bond" motif along the headgroups of the bio-hybrid polyesters, to provide a versatile docking-point for the production of highly functionalised, degradable polymeric platforms; for example in future work via thiol-ene addition chemistry. [38] Functionalisation of the terpene alkene motif in this way has been recently demonstrated by Weems et al in the production of resins using thiols for 'click' reactions, via photopolymerisation.…”