RAFT polymerization of methacrylates containing a tryptophan moiety: controlled synthesis of biocompatible fluorescent cationic chiral polymers with smart pH-responsiveness.

Abstract

Methacrylate monomers having a chiral tryptophan moiety (L- and D-) in the side chain, Boc-tryptophan methacryloyloxyethyl ester (Boc-L/D-Trp-HEMA), have been polymerized by the reversible addition-fragmentation chain transfer (RAFT) process. The controlled nature of RAFT polymerization was evidenced by the well-defined molecular weight and low polydispersity index of the resulting homopolymers and further confirmed to have retained end-group functionality by using these polymers as macro-chain transfer agents (macro-CTAs) to prepare well-defined block copolymers with methyl methacrylate (MMA). The presence of chiral and fluorescent tryptophan moieties in the side-chain of homo- and block-copolymers rendered chiroptical and fluorescence behaviour in them, which was studied through polarimetric measurements and fluorescence spectroscopy, respectively. Successive Boc group deprotection from the polymers produced pH responsive and cationic primary amine moieties at the side chain, which were respectively confirmed by UV-visible spectroscopy and dynamic light scattering (DLS). The in vitro cytotoxicity study using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction (MTT) assay established the cellular viability of HeLa cells in the presence of the poly(Boc-L-Trp-HEMA) homopolymer. The excellent biocompatibility of these fluorescent pH responsive cationic polymers can make them suitable candidates for siRNA delivery.