Engineering Nanoparticle Surface Amphiphilicity: An Integrated Computational and Laser Desorption Ionization Study of Controlled Ligand Self-Assembly

Multi-ligand monolayers can self-organize into advantageous interfacial patterns that govern nanoparticle (NP) properties. Polyethylene glycol (PEG) is widely incorporated into self-assembled monolayers (SAMs) to enhance bio-compatibility, particularly in drug delivery applications. Previous studies demonstrate that monolayer phase separation can be controlled by leveraging the energetic and entropic driving forces acting on ligands in the design of amphiphilic surfaces. In this work, we extend an integrated experimental and simulation framework to investigate the self-assembly of dodecanethiol (DDT), a long hydrophobic alkanethiol, with 2-ethoxyethane-1-thiol, a short hydrophilic PEG-thiol, as a function of their surface composition on ultrasmall gold NPs. The PEG-DDT Au NPs were synthesized via ligand exchange. Integrated MALDI-MS experiments and configurationally biased Monte Carlo (CBMC) simulations were used to analyze and predict the local ordering of the surface ligands. The MALDI-MS fragment distributions obtained from experiment and simulation show quantitative agreement, and both indicate that the PEG-DDT ligands undergo phase separation resulting in NP monolayers with patchy to Janus-like hydrophilic and hydrophobic ligand domains. Further, the domain size was found to increase proportionally with the surface fraction of each ligand, thereby demonstrating the ability to tune patch sizes in amphiphilic monolayers by controlling the surface composition.