Glycopolymer Brushes by Reversible Deactivation Radical Polymerization: Preparation, Applications, and Future Challenges

Abstract

The cellular surface contains specific proteins, also known as lectins, that are carbohydrates receptors involved in different biological events, such as cell-cell adhesion, cell recognition and cell differentiation. The synthesis of well-defined polymers containing carbohydrate units, known as glycopolymers, by reversible deactivation radical polymerization (RDRP) methods allows the development of tailor-made materials with high affinity for lectins because of their multivalent interaction. These polymers are promising candidates for the biomedical field, namely as novel diagnostic disease markers, biosensors, or carriers for tumor-targeted therapy. Although linear glycopolymers are extensively studied for lectin recognition, branched glycopolymeric structures, such as polymer brushes can establish stronger interactions with lectins. This specific glycopolymer topology can be synthesized in a bottlebrush form or grafted to/from surfaces by using RDRP methods, allowing a precise control over molecular weight, grafting density, and brush thickness. Here, the preparation and application of glycopolymer brushes is critically discussed and future research directions on this topic are suggested.

Keywords: brush-like polymers; glycopolymer; lectin binding; reversible deactivation radical polymerization.

Figure 1

Schematic representation of the binding between lectins and one carbohydrate (monovalent binding) or two or more carbohydrates (multivalent binding).

Figure 2

Schematic representation of the binding between a lectin and a glycopolymer brush chain by the multivalent effect.

Figure 3

Available strategies for the preparation of polymeric bottlebrushes or immobilized polymer brushes by RDRP techniques: “grafting from”, “grafting to”, and “grafting through”.

Figure 4

Chemical structure of N-methyl-d-glucamine (1) and protected and non-protected glucose-based vinyl monomers used for the synthesis of polymer brushes by RDRP. 2: methacryloyloxyethyl d-glucopyranoside; 3: d-gluconamidoethyl methacrylate; 4: 2′-acrylamidoethyl-β-d-glucopyranoside; 5: 3-O-methacryloyl-1,2:5,6-di-O-isopropylidene-d-glucofuranose; 6: 2-(2′,3′,4′,6′,-treta-O-acetyl-β-d-glucosyloxy)ethyl methacrylate; 7: 6-O-methacryloyl-α-d-glucoside; 8: 2-{[(d-glucosamine-2-N-yl)carbonyl] oxy}ethyl methacrylate; 9: 2-{[(d-glucosamine-2-N-yl)carbonyl] oxy}ethyl acrylate; 10: N-acryloyl glucosamine; 11: 2′-acrylamidoethyl-1-thio-β-d-glucopyranoside; 12: p-acrylamidophenyl 3,4,6-tri-O-acetyl N-acetyl-glucosamine; 13: 4-vinylbenzenesulfonamidoethyl 1-thio-β-d-glucopyranoside; 14: 4-vinylbenzenesulfonamidoethyl 1-thio-β-d-lactoside; 15: 2-(2-,3-,4-,6-tetra-O-acetyl-β-d-glucosyloxy) ethyl methacrylate.

Figure 5

Specific protein interaction of BSA, Fb, and Con A with different glucose-based brushes.

Figure 6

Interaction of β-amyloid with different polymer brushes. (A): influence of the presence of the sulfate group on the glycopolymer; (B): non-specific interaction of PMA and PDMAEMA by hydrogen bonding and electrostatic interactions, respectively.

Figure 7

Structures of protected and non-protected mannose-based vinyl monomers used for the synthesis of polymer brushes by RDRP. 16: 2′-acrylamidoethyl-α-d-mannopyranoside; 17: p-acrylamidophenyl 2,3,4,6-tretra-O-acetyl-α-d-mannopyroside; 18: 2-methacryloyloxyethyl d-mannopyroside; 19: 2′-acrylamidoethyl 2,3,4,6-tetra-O-acetyl-α-d-mannopyranoside; 20: 2′-acrylamidoethyl-1-thio-(2)-d-mannopyranoside.

Figure 8

Schematic representation of the synthesis of oxazoline-based and mannose-containing linear and bottlebrushes copolymers. (A): Synthesis of copolymer bottlebrushes by combination of CROP with RDRP techniques; (B): representation of random and block linear copolymers; (C): representation of the different bottlebrushes with side chains of vary compositions, namely homopolymers (glycopolymer and PNIPAAm), random and block copolymers [89].

Figure 9

Structures of antiviral glycopolymer brushes prepared by combination chemical vapor deposition polymerization and SI-ATRP: (i) and (ii) reference polymer and correspondent mannose-based glycopolymer brush, respectively; (iii) and (iv) reference copolymer and correspondent mannose-based glycopolymer brush, respectively [18].

Figure 10

Chemical structure of galactose-based vinyl monomers used for the synthesis of polymer brushes by RDRP. 21: 2′-acrylamidoethyl-6β-d-galactopyranoside; 22: 2-lactobionamidoethyl methacrylate; 23: 6-O-methacryloyl-1,2:3,4-di-O-isopropylidene-d-galactopyranose; 24: N-[2-(4-vinylbenzenesulfoneamido)ethyl] lactobioneamide.

Figure 11

pH-responsive behavior of PMAGal-b-PDMAEMA block copolymer brushes at T > LCST.

Figure 12

Preparation of a glycol(co)polymer brush by the combination of ATRP and ROP polymerization techniques.

Figure 13

Chemical structure of maltose (25) and sorbitol methacrylate (26) used for the synthesis of polymer brushes by RDRP.