Facile Synthesis of Hyperbranched Copolymers via an [A₂ + B₃] Click Polymerization Synthesized Reducible Hyperbranched Template

Abstract

Synthesis of multifunctional hyperbranched polymers (HPs) with simultaneously precisely modulated degrees of branch (DBs) and multibiorelevant signal-triggered sensitivities generally suffers from multistep preparation and purification procedures and uncontrolled DB. To develop a facile yet robust approach toward multifunctional HPs with a precisely modulated DB, we reported herein the synthesis of a reducible hyperbranched polymer template (HPT) with a fixed DB via an [A 2 + B 3 ]-based click polymerization and its further mediation of reversible addition−fragmentation chain transfer (RAFT) polymerization for the facile preparation of well-defined multifunctional HPs with a uniform DB, predetermined polymer compositions, and wellmodulated molecular weights (MWs) and low dispersity (Đ) indexes. The breakthrough of this study is the design of a bioreducible HPT-based multimacro chain transfer agent (multimacro-CTA) with a fixed DB of 0.45 via click polymerization between an A 2 unit containing a central trithiocarbonate group for further conduction of RAFT polymerization of any vinyl-based monomers, two disulfide links for reduction sensitivity, and two azide groups and a branched B 3 unit with three highly reactive alkynyl functions. The resulting HPT was further adopted as a multimacro-CTA to mediate RAFT polymerization of a previously reported acidic pH cleavable oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) monomer, α-OEGMA, affording reduction and acidic pH dual sensitive HPT-P(α-OEGMA). Notably, the resulting polymer panel of HPT-P(α-OEGMA)s could self-assemble into stabilized unimolecular micelles with MW-dependent mean hydrodynamic size in a range from 18.9 to 27.0 nm. The drug-loaded HPT-P(α-OEGMA) micelles incubated in a reducing or an acidic pH condition showed accelerated drug release due to the reduction-triggered cleavage of the disulfide links or an acidic pH induced breakage of the acetal links for polymer degradation. Therefore, the universal HPT platform provides a facile yet robust approach toward well-defined multifunctional HPs with a uniform DB, well-controlled MWs, and low Đ indexes for biomedical applications.

Metal-free polycyclotrimerization of trimethylsilyl-protected diynes: a facile strategy toward regioregular hyperbranched polyarylenes

“…1 Hyperbranched polymers (HBPs) have attracted much attention during the past decades due to their three-dimensional globular architectures, unique properties, and wide applications in optoelectronic and biomedical materials, supramolecular chemistry, and so on. [2][3][4][5][6][7][8] Thanks to the unremitting efforts of polymer chemists, numerous synthetic strategies, such as polycondensation, [9][10][11][12] self-condensation vinyl polymerization, [13][14][15] ring-opening polymerization, [16][17][18][19] polycycloaddition, 20,21 controlled/living polymerization, 22,23 and click polymerization, [24][25][26][27] have been developed for the synthesis of HBPs with diverse structures and functional properties.…”

Nickel-Catalyzed Azide–Alkyne Click Polymerization toward 1,5-Regioregular Polytriazoles

“…A turnaround took place in 2002 when the Cu­(I)-catalyzed azide–alkyne cycloaddition (CuAAC) was reported independently by Sharpless et al and Meldal et al , As a typical click reaction, CuAAC could produce sole 1,4-disubstituted 1,2,3-triazoles in excellent yields under mild conditions, which has been developed into a useful polymerization technique, i.e., Cu­(I)-catalyzed azide–alkyne click polymerization (CuAACP) . Thanks to its remarkable click features, CuAACP has been widely used for the preparation of 1,4-regioregular polytriazoles (PTAs) with advanced structures and desired functional properties, which could serve as biomaterials, photoelectric materials, nonlinear optical materials, shape memory materials, self-healing materials, − and so on. To avoid the detriment of the residue metallic species to the optoelectronic and bioapplication of the product, metal-free click polymerization (MFCP) of azides and alkynes was also reported by our groups for the preparation of 1,4-regioregular PTAs …”

Facile synthesis and self-assembly behaviors of biodegradable amphiphilic hyperbranched copolymers with reducible poly(caprolactone) grafts

“…[16][17][18] Different synthetic approaches that have been developed for stimuli-responsive biodegradable hyperbranched copolymers (SBHPs) include post-modification of commercial hyperbranched polymers, such as Boltorn family members, 14,15,19 and polymerization of stimuli-responsive monomers via stepgrowth polymerization or chain-growth polymerization techniques. [20][21][22] Notable examples are Yan's biodegradable amphiphilic hyperbranched multiarm copolymers with disulfide linkages placed between a poly(L-lactide) core and polyphosphate arms by post-modification of H40 via a "grafting to" approach, 14 and Ye's amphiphilic long-subchain hyperbranched copolymer synthesized via step-growth polymerization using a reduction-sensitive polycaprolactone (PCL)-based AB 2 macromonomer. 21 However, both strategies suffered from sophisticated chemical design and multistep preparation procedures, which hampers clearly the potential biomedical applications of materials.…”

“…13 To further improve the biodegradation of PCL for enhanced on-demand release of encapsulated cargoes, preparing PCL monomer-based SBHPs with both stimuli-responsive linear and dendritic units will be a useful strategy. 22 For this purpose, we reported in this study the design and synthesis of a reducible macromonomer, HSEMA-g-PCL, that integrates polymerizable vinyl and hydrophobic poly(ε-caprolactone) (PCL) units via a disulfide link. To provide an insight into the effect of block distribution and polymer composition on the self-assembly behaviors of SBHPs, two types of biodegradable amphiphilic hyperbranched copolymers, i.e., a hyperbranched statistical copolymer h-P(OEGMA-st-(HSEMA-g-PCL)) and a hyperbranched block-statistical copolymer h-P (HSEMA-g-PCL)-b-POEGMA, with an identical polymer composition but different polymer architectures were prepared via the RAFT-SCVP process.…”

“…13 To further improve the biodegradation of PCL for enhanced on-demand release of encapsulated cargoes, preparing PCL monomer-based SBHPs with both stimuli-responsive linear and dendritic units will be a useful strategy. 22…”