“Patchy particles”, where the surface is anisotropically patterned through variation in the surface composition, can assemble into different colloidal crystal structures as well as act as interface stabilizers, heterogeneous reaction catalysts, and targeted drug delivery agents. Patchy nanoparticles (NPs) can be formed by adsorbing two chemically different polymer chains that will spontaneously phase separate. Although there is growing interest in polymer-based patchy nanoparticles, the majority of the studies have been theoretical rather than experimental due to difficulties in preparing significant quantities of nanoparticles with controlled polymer ratios. Likewise, characterization of the phase separation on the nanoparticle surface is challenging. Here we simultaneously overcome the synthesis and characterization hurdles by developing a facile, versatile protocol to produce sufficient quantities of patchy NPs for quantitative solid-state NMR measurements of the patch fractions, degree of phase separation, and morphology. Monodisperse 3.5 nm ZrO2 nanocrystals with polystyrene (PS) and poly­(ethylene oxide) (PEO) ligands, covering the entire possible composition range, were reproducibly prepared through a simple exchange process. This approach has the advantage of well-defined polymer molecular weights and NP sizes, allowing experimental validation of theoretical predictions for nanophase separation in NPs with mixed homopolymer brushes. Upon exposure to a nonselective solvent, the nanoparticles assemble into different morphologies, namely micelles and vesicles, as a function of the PEO:PS ratios.

Spontaneous phase separation in binary mixed ligand shells is a proposed strategy to create patchy nanoparticles. The surface anisotropy, providing directionality along with interfacial properties emerging from both ligands, is highly desirable for targeted drug delivery, catalysis, and other applications. However, characterization of phase separation on the nanoscale remains quite challenging. Here we have adapted solid-state 1 H spin diffusion NMR experiments designed to detect and quantify spatial heterogeneity in polymeric materials to nanoparticles (NPs) functionalized with mixed short ligands. Janus NPs and physical mixtures of homoligand 3.5 nm diameter ZrO 2 NPs, with aromatic (phenylphosphonic acid, PPA) and aliphatic (oleic acid, OA) ligands, were used to calibrate the 1 H spin diffusion experiments. The Janus NPs, prepared by a facile wax/water Pickering emulsion method, and mixed ligand NPs, produced by ligand exchange, both with 1:1 PPA:OA ligand compositions, display strikingly different solvent and particle−particle interactions. 1 H spin diffusion NMR experiments are most consistent with a lamellar surface pattern for the mixed ligand ZrO 2 NPs. Solid-state 1 H spin diffusion NMR is shown to be a valuable additional characterization tool for mixed ligand NPs, as it not only detects the presence of nanoscale phase separation but also allows measurement of the domain sizes and geometries of the surface phase separation.

Synthesis of (3-(pyridin-4-yl)propyl)phosphonic acid.Synthesis of (3-(pyridin-4-yl)propyl)phosphonic acid was performed in two steps as shown in scheme S1.Synthesis of diethyl (3-(pyridine-4-yl)propylphosphonate. Lithium diisopropyl amide (LDA) (18.5 ml, 1.2 eq.) was added dropwise to a solution 4-methyl pyridine (Sigma Aldrich) (1.5 ml, 15.25 mmol, 1 eq.) in 30 ml dry THF at -30 o C under an inert atmosphere. After the reaction mixture was stirred at low temperature for 3 h, diethyl 2-bromoethyl phosphonate (2.85 ml, 15.25 mmol, 1 eq.) was added as a solution in 20 ml dry THF. The reaction mixture was allowed to reach room temperature overnight then was portioned between water and chloroform. The organic layer was separated, dried over MgSO4 and concentrated. The crude product was purified by column chromatography (SiO2, dichloromethane: methanol, 24 : 1 (v : v)). The fractions with Rf = 0.15 were separated to give 1.91 g of diethyl (3-(pyridine-4-yl)propylphosphonate (h = 0.48).