Ligand impact on reactive oxygen species generation of Au10 and Au25 nanoclusters upon one- and two-photon excitation

Atomically precise thiolate-protected gold nanoclusters present strong near-infrared excitation, long lifetimes, and surface biofunctionality, making them ideal candidates as photosensitizers in photodynamic therapy. Here, the authors evaluate the influence of the ligands and metal core on the efficiency of photoexcited Au-10 and Au-25 clusters to produce reactive oxygen species, as well as possible biological consequences in living cells. In photodynamic therapy (PDT), light-sensitive photosensitizers produce reactive oxygen species (ROS) after irradiation in the presence of oxygen. Atomically-precise thiolate-protected gold nanoclusters are molecule-like nanostructures with discrete energy levels presenting long lifetimes, surface biofunctionality, and strong near-infrared excitation ideal for ROS generation in PDT. We directly compare thiolate-gold macromolecular complexes (Au-10) and atomically-precise gold nanoclusters (Au-25), and investigate the influence of ligands on their photoexcitation. With the ability of atomically-precise nanochemistry, we produce Au(10)SG(10), Au(10)AcCys(10), Au(25)SG(18), and Au(25)AcCys(18) (SG: glutathione; AcCys: N-acetyl-cysteine) fully characterized by high-resolution mass spectrometry. Our theoretical investigation reveals key factors (energetics of excited states and structural influence of surface ligands) and their relative importance in singlet oxygen formation upon one- and two-photon excitation. Finally, we explore ROS generation by gold nanoclusters in living cells with one- and two-photon excitation. Our study presents in-depth analyses of events within gold nanoclusters when photo-excited both in the linear and nonlinear optical regimes, and possible biological consequences in cells.