Facile Preparation of Well-Defined AB₂ Y-Shaped Miktoarm Star Polypeptide Copolymer via the Combination of Ring-Opening Polymerization and Click Chemistry

Abstract

Well-defined AB2 Y-shaped miktoarm star polypeptide copolymer, PZLL-b-(PBLG)2, was synthesized via a combination of ring-opening polymerization (ROP) of alpha-amino acid N-carboxyanhydride (NCA) and click chemistry, where PZLL is poly(epsilon-benzyloxycarbonyl-L-lysine) and PBLG is poly(gamma-benzyl-L-glutamate). First, two types of primary-amine-containing initiators, N-aminoethyl 3,5-bis(propargyloxyl)-benzamide and 3-azidopropylamine, were synthesized and employed for the ROP of NCA, leading to the formation of dialkynyl-terminated PZLL and azide-terminated PBLG, dialkynyl-PZLL and PBLG-N3, respectively. The subsequent copper(I)-catalyzed cycloaddition reaction between dialkynyl-PZLL and slightly excess PBLG-N3 led to facile preparation of PZLL-b-(PBLG)2 Y-shaped miktoarm star polypeptide copolymer. The excess PBLG-N3 was scavenged off by reacting with alkynyl-functionalized Wang resin. The obtained Y-shaped miktoarm star polypeptide copolymer was characterized by gel permeation chromatograph (GPC), Fourier transform-infrared spectroscopy (FT-IR), and (1)H NMR. Moreover, after the hydrolysis of protecting benzyl and benzyloxycarbonyl groups of PZLL-b-(PBLG)2, water-soluble pH-responsive Y-shaped miktoarm star polypeptide copolymer, PLL-b-(PLGA)2, was obtained, where PLL is poly(L-lysine) and PLGA is poly(L-glutamic acid). It can self-assemble into PLGA-core micelles at acidic pH and PLL-core micelles at alkaline pH, accompanied with the coil-to-helix transition of PLGA and PLL sequences, respectively. The spontaneous pH-responsive supramolecular assembly of PLL-b-(PLGA)2 miktoarm star polypeptide copolymer has been investigated via a combination of (1)H NMR, laser light scattering (LLS), transmission electron microscopy (TEM), and circular dichroism (CD) spectroscopy.

Synthesis and Characterization of Biodegradable Amphiphilic Star and Y-Shaped Block Copolymers as Potential Carriers for Vinorelbine

“…Y-shaped block copolymers are another interesting vehicle for drug delivery since they exhibit different micellization behavior (especially stability) compared to the traditional amphiphilic materials [19][20][21][22]. However, it is still a challenge to prepare biodegradable Y-shaped block copolymers.…”

Synthesis of Amphiphilic Tadpole-Shaped Linear-Cyclic Diblock Copolymers via Ring-Opening Polymerization Directly Initiating from Cyclic Precursors and Their Application as Drug Nanocarriers

“…[1][2][3] It has been well-established that the topological structures and chemical composition of nonlinearshaped block copolymers can exhibit dramatic effects on the solution properties and self-assembling morphologies as compared with their linear counterpart. [4][5][6][7][8][9] It is worthy of noting that the developments of a variety of controlled radical polymerization techniques 10 such as atom transfer radical polymerization (ATRP), [11][12][13] reversible addition-fragmentation chain transfer (RAFT) polymerization, [14][15][16] and nitroxide-mediated polymerization (NMP) 17,18 have facilitated the synthesis of nonlinear-shaped polymers with varying chain architectures such as cyclic, 8,9,[19][20][21][22][23] (miktoarm) star, [24][25][26] star block copolymers, 27,28 comb, [29][30][31][32] sun-shaped, [33][34][35] H-shaped, [36][37][38] and θ-shaped 39,40 polymers. Among these nonlinear chain topologies, tadpole-shaped linearcyclic diblock copolymers [41]…”

Synthesis of amphiphilic and thermoresponsive ABC miktoarm star terpolymer via a combination of consecutive click reactions and atom transfer radical polymerization

“…Our research interests involve the controlled synthesis of responsive block copolymers and their supramolecular self-assembly in aqueous solution. [31][32][33][34] In this work, we synthesized a novel ABC miktoarm star terpolymer consisting of hydrophilic PEG, hydrophobic poly(tert-butyl methacrylate) (PtBMA), and thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) arms via a combination of consecutive click reactions and ATRP, starting from bis(2-azidoethyl)amine, (N 3 ) 2 ANH, which contains two azide groups and one secondary amine moiety (Schemes 1 and 2). We then investigated the supramolecular self-assembly behavior of PEG(-b-PtBMA)-b-PNIPAM miktoarm star terpolymer in aqueous solution.…”