Particle modification 95

Much work has been done on the functionalization of polymers using thiol- ene chemistry.32, 33, 37-39 Herein we focus on the use of such chemistry to modify particles.

Polymerization of difunctional monomer species results in polymers with pendant vinyl groups; these can be exploited by thiol-ene click chemistry.40, 41 Poly(divinylbenzene) particles are a common substrate for such reactions, due to their well understood characterization and ease of synthesis via precipitation polymerization.42, 43 _{Radical thiol-ene chemistry has been widely employed for the}

modification of such functionalized particles using both thermal and photo-initiator pathways. Hawker and co-workers utilized thiol-ene click chemistry to modify multimodal composite poly(divinylbenzene) particles in order to disperse them in various organic media.44, 45 Charge stabilized poly(divinylbenzene) particles containing MnFe2O4 and Au nanoparticles were synthesized by miniemulsion

polymerization in water (Figure 3.4 a); on redispersion in THF the particles were found to be unstable. By reacting the pendant vinyl groups on the surface of the poly(divinyl benzene) particle with thiol functionalized PEG, using a thermal radical initiator (V-50), particles were found to be dispersible in a number of solvents including water, THF, chloroform and DMF (Figure 3.4 b).

Figure 3.4 (a) TEM image of composite multimodal composite poly(divinylbenzene)-inorganic latex

particles prepared by co-encapsulation of MnFe2O4 and Au nanoparticles and (b) photograph of

composite latex particles redispersed in THF; (left) before and (right) after attachment of PEG.44 Aiding particle dispersion is a common goal in the surface modification of particles. Mecking et al. post-functionalised poly(butadiene) particles with various hydrophilic moieties; including 3-mercaptopropionic acid methyl ester, 3- mercapatopropanesulfonic acid sodium salt and glutathione (Figure 3.5).46 Modification was achieved using a thermal radical initiator, in order to produce stable nanoparticles which were redispersible in water. Grafting of the more polar mercaptans (glutathione and 3-mercapatopropanesulfonic acid sodium salt) resulted in modification of the surface pendant vinyl groups on the poly(butadiene) particles. Using less polar mercaptans (3-mercaptopropionic acid methyl ester) resulted in complete conversion of all vinyl groups, due to permeability of the thiol into the polymer particle.

Figure 3.5 (1) 3-mercaptopropionic acid methyl ester, (2) 3-mercapatopropanesulfonic acid sodium

salt and (3) glutathione.

The grafting of polymers prepared by RAFT has proven a popular tool as highly controlled and well defined polymers can be converted to thiol ω-end functional polymers via aminolysis.47 Müller and co-workers modified

poly(divinylbenzene) particles, prepared by precipitation polymerization in acetonitrile, with poly(NIPAAm) in order to produce particles which were dispersible in water and had thermo-responsive behaviour.48 _{Thiol functionalized}

poly(NIPAAm) was prepared by RAFT polymerization and cleavage of the RAFT group to yield a thiol using NaBH4; the subsequent grafting reaction proceeded by

radical thiol-ene click using AIBN as an initiator. In a similar manner, Kang et al.

prepared fluorescent hollow particles with temperature responsive brushes.49 Encapsulation of silica nanoparticles in poly(divinylbenzene-co-n-vinylcarbazole) was followed by AIBN initiated click of thiol functionalized poly(NIPAM) to the pendant vinyl groups; where poly(NIPAAm) was prepared by RAFT polymerization followed by reduction of the RAFT group using NaBH4. The silica core was etched

out with hydrofluoric acid to yield multifunctional hollow particles.

Caruso and co-workers prepared hollow particles by layer-by layer assembly, where thiol-ene chemistry was used to cross-link polymer layers and to functionalize the surface with PEG to achieve anti-fouling properties.50 Silica particles were encapsulated by LbL assembly of poly(methacrylic acid) containing either thiol or ene functionality with poly(vinylpyrrolidone), using UV-light as an initiator (thiol self-initiates forming a radical). Thiol-ene chemistry was used to cross-link the poly(methacrylate) layers and the silica was etched out on addition of hydrofluoric acid and on increasing the pH to 7 the non-cross-linked layers of poly(vinylpyrrolidone) were released. The particles were further reacted with ene functionalized PEG, again using UV light, to create the thiyl radical to achieve the anti-fouling finish (Figure 3.6). Yogo and co-workers modified Fe3O4 nanoparticles

radical click chemistry of cysteine using AIBN, for use in biomedical applications such as an MRI contrast agent.51

Figure 3.6 Preparation of (PVP/PMAThiol/PVP/PMAEne)-coated particles, (1-2) PEGylation and

stabilization using thiol-ene chemistry, (3) removal of silica core and (4) removal of PVP.50

Though not as widely employed as the radical thiol-ene reaction, the thiol- ene Michael addition has also been used in polymer synthesis and modification. Stenzel and co-workers synthesized ethylene glycol dimethacrylate (EGDMA) particles by suspension polymerization and subsequently surface modified them with glucothiose to achieve bioactive particles using tris(2-carboxyethyl)phosphine (TCEP) as the nucleophilic catalyst.52 Boyer and co-workers used thiol-ene chemistry to modify the surface of titanium dioxide nanoparticles with polymeric chains to aid dispersibility in biological media and aid cell uptake.53 The TiO2

nanoparticles were modified to yield surface thiol groups by functionalizing with (3- mercaptopropyl) trimethoxysilane, thiol Michael addition with poly(oligo(ethylene glycol) methyl ether methacrylate) comb polymers with vinyl functionality (prepared by catalytic chain transfer) was achieved using hexylamine as a nucleophilic catalyst in acetonitrile (Figure 3.7).

Figure 3.7 Overall synthetic approach for the surface modification of TiO2 nanoparticles.53

In this body of work we describe the encapsulation of calcium carbonate particles with multi-functional acrylate monomers to achieve particles with pendant vinyl groups. Utilizing the pendant vinyl groups to modify the particles with thiol “click” chemistry, we demonstrate both hydrophilic and hydrophobic modification and the Michael addition of thiol functionalized poly(styrene) synthesized by RAFT polymerization.