Nanoparticle Ligand Exchange via Phase Transfer Using Sterically Encumbered <i>m</i>-Terphenyl Isocyanides

Ligand exchange via phase transfer (LEPT) is a highly utilized process for the surface functionalization of colloidal nanoparticles (NPs) across various fields. LEPT involves the displacement of the native ligands on NPs to enhance their solvent dispersibility, colloidal stability, and biocompatibility while enabling the efficient extraction of functionalized NPs by employing immiscible solvents for the exchange process. While LEPT is commonly employed in the postsynthetic processing of NPs where uniform NP passivation is desired, achieving selective NP surface ligation remains a challenge. This work investigates the LEPT mechanism and parameters influencing NP functionalization with <i>m</i>-terphenyl isocyanide ligands, which have been previously demonstrated for NP size separation and size focusing. Herein, we offer a detailed examination of the extraction efficiency of gold nanospheres (AuNSs) from water to organic solvents using LEPT. Solvent choice, AuNS and ligand concentration, and pH are shown to modify the kinetics of LEPT, which deviate from prior theoretical predictions based solely on ligand binding energies and molecular solubilities. These insights contribute to a comprehensive understanding of LEPT with <i>m</i>-terphenyl isocyanides, offering pathways for the development of tailored NP extraction and separation methods that improve NP utility and performance.