Novel Strategy for ROP of NCAs Using Thiols As Initiators: Synthesis of Diblock Copolymers Based on Polypeptides

Abstract

International audienceThe ring opening polymerization (ROP) of γ-benzyl-L-glutamate N-carboxyanhybride (BLG-NCA) and Nε-trifluroactetyl-L-lysine N-carboxyanhybride (TFALys-NCA) by thiol was investigated at 0°C in DMF as solvent. The use of 2-(trimethylsilyl)-ethanethiol as initiator and its incorporation in the macromolecular chain showed the efficient ring opening polymerization of BLG-NCA by the so called “amine” mechanism. Thus, we proposed a novel synthetic pathway for the synthesis of diblock copolypeptides [poly(N,Ndiethylacrylamide)- b-poly(γ-benzyl-L-glutamate) and poly(N,N-diethylacrylamide)-bpoly( Nε-trifluoroacetyl-L-lysine)] using thiol based macroinitiator. This last was obtained by cleavage of a dithioester end group of poly(N,N-diethylacrylamide) synthesized by RAFT polymerization

RAFT Polymerization and Thiol Chemistry: A Complementary Pairing for Implementing Modern Macromolecular Design

“…[29] The products of such substitution reactions are thioethers. Thiols can be added to N-carboxyanhydrides [30] or D,Llactide [31] by ring opening the anhydride thus forming a thioester linkage (Table 1). …”

“…A) Formation of three-armed stars through nucleophilic addition onto a core molecule, [84] B) Formation of hairy nanoparticles through a radical addition onto vinyl modified particles, [85] C) Formation of graft polymers through (co)polymerizing macromonomers, [74] and D) Formation of diblock copolymers through a thiol initiated ROP of lactic anhydrides [31] or N-carboxy-anhydrides. [30] See Table 1 for definition of Y.…”

“…These were connected to yield cyclic PNIPAM using azide/ acetylene click chemistry. A novel strategy employing thiol chemistry for producing diblock copolymers has been described by Zhang et al, [30] who used the thiol end-groups of RAFT-prepared PDEAM as initiators for a ring opening polymerization (ROP) of N-carboxyanhydrides. An amine mechanism was proposed for the initiation, where an amine is produced after the first attack of the thiol onto an N-carboxyanhydride.…”

Living Radical Polymerization by the RAFT Process – A Third Update

“…S S * DEAm [273] (VAc) [274] (NVP) [248] EHA-b-MA [275] 39 S S O OH * H A [240] (Continued ) [240] MMA/433 [276] MMA/434 [276] MMA/435 [276] MMA/436 [276] MMA/437 [276] DMAEMA/433 [276] DMAEMA/434 [276] DMAEMA/434 [276] DMAEMA/437 [276] HEMA/433 [276] HEMA/434 [276] HEMA/434 [276] HEMA/437 [276] MAA/PEGMA [277] St/CMS [278] 41…”

End Group Reactions of RAFT-Prepared (Co)Polymers

“…[163,164] Lefay et al [164] used thiol-terminated PSty (PSty-SH) to initiate the ROP of D,L-lactide under 4-(dimethylamino) pyridine (DMAP) catalysis. Starting from a PSty with an M n of 6100 and a polydispersity index of 1.2, diblock copolymers with M n s up to 25000 and polydispersity indices between 1.2 and 1.6 were prepared.…”