Linear Amphiphilic Polyglycidol/Poly(ε-caprolactone) Block Copolymers Prepared via “Click” Chemistry-Based Concept

Abstract

We introduce a "click" chemistry-based concept for the preparation of amphiphilic block copolymers comprising linear polyglycidol (PG). Herein, a new class of linear polyglycidol/poly(ε-caprolactone) (PG/PCL) block copolymers of precisely designed macromolecular characteristics and composition was synthesized to demonstrate the convenience of this strategy. Monohydroxyl poly(ethoxyethylglycidyl ether) (PEEGE) precursors were synthesized by ring-opening anionic polymerization of ethoxyethylglycidyl ether (EEGE) and subsequently functionalized with a "clickable" alkyne end group. In parallel, a bifunctional PCL diol was modified to an azide-terminated macroreagent. PG/PCL block copolymers were obtained by "click" coupling reaction of the alkyn-and azide-functional macroreagents in the presence of a CuBr/PMDETA catalytic complex and subsequent cleavage of the protective ethoxyethyl groups of PEEGE. The amphiphilic block copolymers were not directly soluble in water, and defined nano-sized micelles were obtained via the solvent evaporation method. The synthesis pathway described here can be extended toward synthesis of various functional block copolymers comprising linear PG.Recent advances in polymer chemistry have enabled the synthesis of amphiphilic macromolecules with controlled length, topology, and well-defined positions of functional groups along the chain. This offers many possibilities for fabricating desired nanoscale structures with tailored properties by design of novel copolymer molecules. For example, the pioneering works devoted to micellar carriers for nanomedicine have been focused mainly on the formation of core−shell micelles, loading with active substances, and in vitro release studies, while nowadays, more complex functional systems combining a variety of properties and allowing for the simultaneous performance of multiple functions in in vivo conditions are being investigated. 4 It is not unexpected that the spectrum of micellar characteristics such as size, loading capacity, elimination time, cell penetration ability, and drug release profile has been remarkably improved or optimized.

Click chemistry strategies for the accelerated synthesis of functional macromolecules

“…Telechelic or heterotelechelic polymer with clickable groups on both ends can be coupled with polymers containing complementary end groups, resulting in ABA or ABC triblock copolymers. For example, Poly(ethoxyethyl glycidyl ether)‐ block ‐Poly(ε‐caprolactone)‐ block ‐Poly(ethoxyethyl glycidyl ether) (PEEGE‐ b ‐PCL‐ b ‐PEEGE) triblock copolymer was synthesized by CuAAC between diazide‐functionalized PCL middle block and alkyne terminated PEEGE 671 . Similarly, Tunca and coworkers applied CuAAC and DA in constructing ABC triblock copolymers, by using α‐anthracene, ω‐azide terminated PS as a heterotelechelic polymer 333 .…”

Tailor-Made Functional Polyolefins of Complex Architectures: Recent Advances, Applications, and Prospects

“…Hadjichristidis et al designed and synthesized well-defined AB 2 type 3-miktoarm star copolymers of ethylene and ε-caprolactone [3 μ-HBPE (PCL) 2 ] using successive CWP, ROMP, and azide–alkyne cycloaddition click chemistry, as shown in Figure . The star copolymers of poly­[ε-caprolactone] (PCL) are widely used in biomedical applications, − drug delivery systems, nanoelectronics, , and polymers modification , thanks to their ability to form self-assemblies and micelles in selective solvents . Moreover, both the alkyne-containing PCL and azide-functionalized HBPE are valuable precursors for synthesizing complex tailor-made PCL and HBPE-based architectures, respectively.…”

Advances, Challenges, and Opportunities of Poly(γ-butyrolactone)-Based Recyclable Polymers

“…To further improve the polymer performance, copolymerization was utilized as an effective strategy to tailor material property by the combination of certain desirable characteristics of two or more homopolymers. − Based on the advances of efficient polymerization of GBL at low temperature and high monomer concentration, ring-opening copolymerizations (ROCOP) of nonstrained GBL and high-strained cyclic monomers achieved progress to prepare block and random copolymers with controlled structures and varied properties (Figure ). It is notable that the utilization of a comonomer contributed to an elevation of polymerization temperature above the ceiling temperature. − For example, the addition of comonomer ε-caprolactone (ε-CL) enabled the copolymerization at room temperature, and copolymers with molecular weights up to 135 kg/mol were obtained .…”