New Route to Polymeric Nanoparticles by Click Chemistry Using Bifunctional Cross‐Linkers

Abstract

A new route to functional polymeric nanoparticles (PNPs) of different chemical nature in the 3 to 20 nm size range is reported by combining both radical addition fragmentation chain transfer (RAFT) polymerization and “click” chemistry (CC) techniques. RAFT polymerization was employed for the synthesis of well‐defined statistical copolymers with pending –Cl groups along the macromolecular chain. After transformation of the –Cl groups to –N3 groups by treatment with sodium azide, an appropriate bifunctional cross‐linker is employed to obtain PNPs under CC conditions promoting intramolecular cycloaddition (cross‐linking). Following this new route, polystyrene, poly(alkyl (meth)acrylate), polymethacrylic acid, poly(sodium styrenesulfonate) and poly(N‐isopropyl) NPs have been synthesized and in‐deep characterized.

Advances in Click Chemistry for Single-Chain Nanoparticle Construction

“…I agree with the suggested changes, that can be made easily by the editorial office. [7,22,28,29], poly(styrene) [3,22,23,[30][31][32], poly(haloalkyl styrene) [3,33], poly(4-N-Boc-vinylaniline) [33], poly(sodium 4-styrenesulfonate) [22], poly(N-alkyl acrylamide) [22,34,35] Atom transfer radical polymerization ATRP Poly(alkyl methacrylates) [14], poly(alkyl acrylates) [11,12], poly(styrene) [36], poly(N-hydroxyethyl acrylamide) [37] Nitroxide mediated radical polymerization NMP Poly(alkyl methacrylates) [9,[38][39][40], poly(alkyl acrylates) [40], poly(styrene) [2,38,40], poly(haloalkyl styrene) [40], poly(fluorene) [41] Ring opening metathesis polymerization ROMP Poly(-caprolactone) [38], poly(carbonates) [42] poly(norbornenes) [13,43,44] * For SCNP copolymer and terpolymer precursors, only the nature of the main component is indicated.…”

“…Covalent bonding interactions Vinyl [33,38,39,42] Radical coupling & Cross-Metathesis Benzocyclobutene [40,53] Diels-Alder reaction * Benzosulfone [9,28,41] Diels-Alder reaction * Azide + Protected alkyne [3,10,21,22,30,34] Copper-catalyzed [3+2] cycloaddition ** Carboxilic acid [54] Amide formation Isocyanate [23] Urea formation ** Enediyne [11,12,24,29] Bergman & Photo-Bergman cyclization Sulfonyl azide [31] Nitrene-mediated cross-linking Benzoxazine [36] Ring opening polymerization Alkyne [25] Glaser-Hay coupling * * C-C click chemistry. ** N-C click chemistry.…”

Metal-Free Polymethyl Methacrylate (PMMA) Nanoparticles by Enamine “Click” Chemistry at Room Temperature

“…The precursors were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using 2-cyanoprop-2-yl-dithiobenzoate (CDB) as chain transfer agent and 2,2′-azobis(2-methylpropionitrile) (AIBN) as free-radical initiator. RAFT is a very convenient polymerization technique for obtaining nanoparticle precursors with low molecular-weight dispersity [11][12][13] and hence nanoparticles with uniform size. The main characteristics of the random P(MMA-co-AEMA) copolymers investigated in this work are summarized in Table 1, as determined by size exclusion chromatography with absolute molar mass characterization and proton nuclear magnetic resonance spectroscopy.…”

“…Significant efforts have been devoted in recent years to open new routes to unimolecular nanoparticles relying on efficient synthetic methods for the controlled, irreversible intramolecular collapse of individual polymer chains. In this sense, different synthetic approaches have been reported: free-radical cross-linking of vinyl units [6][7][8], thermal cross-linking of benzocyclobutene and o-quinodimethane functional groups by Diels-Alder reactions [9,10], copper-catalyzed azide-alkyne "click" chemistry [11][12][13] and fast cross-linking of isocyanate groups from appropriate precursor chains by diamines [14].…”

“…In an attempt to solve the limitations of the previous techniques, we introduced the macromolecular "click" cycloaddition route [11][12][13] which relies on the use of alkyne and azide functional groups allowing the synthesis of unimolecular NPs by copper-catalyzed azide-alkyne "click" chemistry. Currently, a great interest exists for developing "click" chemistry procedures beyond the copper-catalyzed azide-alkyne cycloaddition [15], allowing the synthesis of "metal-free" unimolecular polymeric nanoparticles at r.t.…”