Reversible control of nanoparticle functionalization and physicochemical properties by dynamic covalent exchange

Abstract

Existing methods for the covalent functionalization of nanoparticles rely on kinetically controlled reactions, and largely lack the sophistication of the preeminent oligonucleotide-based noncovalent strategies. Here we report the application of dynamic covalent chemistry for the reversible modification of nanoparticle (NP) surface functionality, combining the benefits of non-biomolecular covalent chemistry with the favorable features of equilibrium processes. A homogeneous monolayer of nanoparticle-bound hydrazones can undergo quantitative dynamic covalent exchange. The pseudomolecular nature of the NP system allows for the in situ characterization of surface-bound species, and real-time tracking of the exchange reactions. Furthermore, dynamic covalent exchange offers a simple approach for reversibly switching—and subtly tuning—NP properties such as solvophilicity.

Figure 1

Preparation and reversible surface modification of a dynamic covalent NP building block exploiting N-aroylhydrazone surface monolayers.

Figure 2

Synthesis and characterization of AuNP-1. a) Nanoparticle synthesis. 1) AuPPh₃Cl, borane tert-butylamine complex, DMF/THF 1:9, RT, 6 h. b) ¹H NMR spectra ([D₇]DMF, 500.1 MHz, 295 K): 1₂ (top); AuNP-1 (middle); AuNP-1­ T₂-filtered spectrum (bottom). Signals at 8.02, 3.50, 2.92, and 2.75 ppm correspond to residual nondeuterated solvent and water. c) ¹⁹F NMR spectra ([D₇]DMF, 470.5 MHz, 295 K): 1₂ (top); AuNP-1 (bottom). d) Size distribution of a representative batch of AuNP-1 (mean diameter 3.39±0.61 nm). e) UV/Vis spectrum of AuNP-1 in DMF (SPR λ_max=509 nm). f) LDI-MS of AuNP-1.

Figure 3

a) Hydrazone exchange between AuNP-1 and AuNP-2. Conditions: aldehyde (20 equiv with respect to 1), CF₃CO₂H (5 equiv with respect to 1), D₂O/[D₇]DMF 1:9, 50 °C. b) Partial ¹⁹F NMR spectra ([D₇]DMF, 470.5 MHz, 295 K), from top to bottom: AuNP-1; AuNP-1_0.12_0.9; AuNP-2; 1_0.52_0.5; AuNP-1_0.742_0.26 . c) Partial LDI-MS spectra of AuNP-1 (top), AuNP-2 (middle), and AuNP-1_0.742_0.26 (bottom).

Figure 4

Reversible switching of AuNP solvophilicity properties by hydrazone exchange. For full conditions, see the SI, Section 11. Solvents in the inset pictures: A=hexane, B=chloroform, C=tetrahydrofuran, D=methanol, E=DMF, F=water.