Protected Poly(3-sulfopropyl methacrylate) Copolymers: Synthesis, Stability, and Orthogonal Deprotection

Abstract

Because of their permanent charge, strong polyelectrolytes remain challenging to characterize, in particular, when they are combined with hydrophobic features. For this reason, they are typically prepared through a postmodification of a fully hydrophobic precursor. Unfortunately, these routes often result in an incomplete functionalization or otherwise require harsh reaction conditions, thus limiting their applicability. To overcome these problems, in this work a strategy is presented that facilitates the preparation of well-defined strong polyanions by starting from protected 3-sulfopropyl methacrylate monomers. Depending on the chemistry of the protecting group, the hydrophobic precursor could be quantitatively converted into a strong polyanion under nucleophilic, acidic, or basic conditions. As a proof of concept, orthogonally protected diblock copolymers were synthesized, selectively deprotected, and allowed to self-assemble in aqueous solution. Further conversion into a fully water-soluble polyanion was achieved by deprotecting the second block as well.

Scheme 1. General Reaction Scheme and Schematic Illustration Describing the Strategy for the Synthesis and Deprotection of the Hydrophobic Polymeric Precursors

Depending on the deprotecting conditions, the strong polyanion (PSPMA) is obtained as either the sulfonate salt or sulfonic acid. This work describes four different protecting groups (R = isobutyl, phenyl, neopentyl, and HFIP), resulting in PBSPMA, PPhSPMA, PNSPMA, and PFSPMA after polymerization, respectively.

Scheme 2. Schematic Description of the Deprotection of Isobutyl-Protected (PBSPMA), Neopentyl-Protected (PNSPMA), Phenyl-Protected (PPhSPMA), and Hexafluoroisopropyl-Protected (PFSPMA) Poly(3-sulfopropyl methacrylates)

Figure 1

¹H NMR spectra of RAFT-synthesized homopolymers before and after deprotection. (a) PBSPMA treated with NaI (weak nucleophile), (b) PPhSPMA with NaOH (base), and (c) PNSPMA with NaN₃ (strong nucleophile). (d) PFSPMA’s protecting group could not be removed under the tested conditions. All spectra were recorded in DMSO-d₆.

Scheme 3. General Reaction Scheme and Schematic Illustration Describing the Route towards Orthogonally Protected Diblock Copolymers through RAFT Polymerization

Figure 2

GPC elugrams and ¹H NMR spectra (CDCl₃) of the orthogonally protected diblock copolymers. (a, b) PNeo-b-PPh, (c, d) PiBu-b-PPh, and (e, f) PiBu-b-PNeo. Copolymer compositions were calculated by comparing the signals of the protecting groups.

Scheme 4. Schematic Representation of the Sequential Deprotection of Orthogonally Protected PNeo-b-PPh, PiBu-b-PPh, and PiBu-b-PNeo Diblock Copolymers under Weak Nucleophilic (NaI/PiBu), Strong Nucleophilic (NaN₃/PNeo), or Basic (NaOH/PPh) Conditions

Figure 3

Reaction schemes and ¹H NMR spectra of the stepwise deprotection of the orthogonally protected diblock copolymers: (a) PNeo-b-PPh by NaOH/NaN₃ treatment, (b) PiBu-b-PPh via NaI/NaOH treatment, and (c) PiBu-b-PNeo via reaction with NaI/NaN₃. All spectra were recorded in DMSO-d₆.

Figure 4

(a–c) DLS size distribution plots of the self-assembled micellar aggregates prepared from the partially deprotected diblock copolymers; the deprotected block is underlined. (d–f) Transmission electron micrographs of negatively stained block copolymer aggregates: (d) PNeo-b-PPh, (e) PiBu-b-PPh, and (f) PiBu-b-PNeo. Particles were formed via the solvent addition method. Final composition: 1.0 mg mL^–1, 13 wt % DMSO in H₂O, and 11 mM KNO₃.