Poly(lactide)-block-Poly(HEMA) Block Copolymers: An Orthogonal One-Pot Combination of ROP and ATRP, Using a Bifunctional Initiator

Abstract

We describe an orthogonal polymerization strategy for the preparation of amphiphilic poly(lactide)-block-poly(2-hydroxyethyl methacrylate) (PLA-b-PHEMA) copolymers with a partially biodegradable and a potentially biocompatible polymer backbone segment. The strategy is based on an orthogonal polymerization from a double-headed initiator, which has been realized in a rapid one-pot or in a two-pot route. The “lactide first” strategy permits exclusive chain growth from the hydroxyl group of the initiator, 2-hydroxyethyl 2-bromo-2-methylpropanoate. 2-Hydroxyethyl methacrylate (HEMA) was polymerized in a second step by controlled radical polymerization (ATRP) without the use of hydroxyl protecting groups. Because of the heterogeneous character of the two blocks, ATRP had to be conducted in dimethyl sulfoxide at 80 °C, both granting sufficient solubility for the stereoregular, semicrystalline poly(lactide) block and permitting fast chain growth of the poly(HEMA) block. The PLLA/PDLA macroinitiators were synthesized using Sn(Oct)2 as a catalyst in solution (PDI = 1.07−1.17; Mn = 2000−9000 g/mol). NMR spectroscopy and MALDI-ToF MS confirmed complete terminal functionalization with the bifunctional initiator 2-hydroxyethyl 2-bromo-2-methylpropanoate. Fast growth (<10 min, 45−60% conversion) of the poly(HEMA) block was achieved with a CuCl/bipyridine or CuCl/CuCl2/bipyridene system. SEC measurements indicated complete attachment of the second block resulting in narrow polydispersity of Mw/Mn = 1.2−1.3 (Mn = 5000−9000 g/mol). Developing the concept further, removal of residual lactide monomer and Sn(Oct)2 catalyst has been proven to be redundant by a variation in the synthetic procedure. In consistence with new AGET (activators generated by electron transfer) ATRP methods, grafting of free lactide monomer onto the HEMA backbone could be avoided by oxidative deactivation of Sn(Oct)2 by small amounts of copper(II), obtaining the PLA-b-PHEMA block copolymers in one single step. DSC measurements demonstrate phase segregation of the blocks after cooling from the melt as well as work-up from solution.