Origins of the pH-Responsive Photoluminescence of Peptide-Functionalized Au Nanoclusters.

Ultrasmall peptide-protected gold nanoclusters are a promising class of bioresponsive material exhibiting pH-sensitive photoluminescence. We present a theoretical insight into the effect peptide-ligand environment has on pH-responsive fluorescence, with the aim of enhancing the rational design of gold nanoclusters for bioapplications. Employing a hybrid quantum/classical computational methodology, we systematically calculate deprotonation free energies of N-terminal cysteine amine groups in proximity to the inherently fluorescent core of Au25(Peptide)18 nanoclusters. We find that subtle changes in hexapeptide sequence alter the electrostatic environment and significantly shift the conventional N-terminal amine pKa expected for amino acids free-in-solution. Our findings provide an insight into how the deprotonation equilibrium of N-terminal amine and side chain carboxyl groups cooperatively respond to solution pH changes, explaining the experimentally observed, yet elusive, pH-responsive fluorescence of peptide-functionalized Au25 clusters.

Origins of Structural Elasticity in Metal-Phenolic Networks Probed by Super-Resolution Microscopy and Multiscale Simulations.

Metal-phenolic networks (MPNs) are amorphous materials that can be used to engineer functional films and particles. A fundamental understanding of the heat-driven structural reorganization of MPNs can offer opportunities to rationally tune their properties (e.g., size, permeability, wettability, hydrophobicity) for applications such as drug delivery, sensing, and tissue engineering. Herein, we use a combination of single-molecule localization microscopy, theoretical electronic structure calculations, and all-atom molecular dynamics simulations to demonstrate that MPN plasticity is governed by both the inherent flexibility of the metal (FeIII)-phenolic coordination center and the conformational elasticity of the phenolic building blocks (tannic acid, TA) that make up the metal-organic coordination complex. Thermal treatment (heating to 150 °C) of the flexible TA/FeIII networks induces a considerable increase in the number of aromatic π-π interactions formed among TA moieties and leads to the formation of hydrophobic domains. In the case of MPN capsules, 15 min of heating induces structural rearrangements that cause the capsules to shrink (from ∼4 to ∼3 µm), resulting in a thicker (3-fold), less porous, and higher protein (e.g., bovine serum albumin) affinity MPN shell. In contrast, when a simple polyphenol such as gallic acid is complexed with FeIII to form MPNs, rigid materials that are insensitive to temperature changes are obtained, and negligible structural rearrangement is observed upon heating. These findings are expected to facilitate the rational engineering of versatile TA-based MPN materials with tunable physiochemical properties for diverse applications.

Surface Dynamics and Ligand-Core Interactions of Quantum Sized Photoluminescent Gold Nanoclusters.

Quantum-sized metallic clusters protected by biological ligands represent a new class of luminescent materials; yet the understanding of structural information and photoluminescence origin of these ultrasmall clusters remains a challenge. Herein we systematically study the surface ligand dynamics and ligand-metal core interactions of peptide-protected gold nanoclusters (AuNCs) with combined experimental characterizations and theoretical molecular simulations. We show that the peptide sequence plays an important role in determining the surface peptide structuring, interfacial water dynamics and ligand-Au core interaction, which can be tailored by controlling peptide acetylation, constituent amino acid electron donating/withdrawing capacity, aromaticity/hydrophobicity and by adjusting environmental pH. Specifically, emission enhancement is achieved through increasing the electron density of surface ligands in proximity to the Au core, discouraging photoinduced quenching, and by reducing the amount of surface-bound water molecules. These findings provide key design principles for understanding the surface dynamics of peptide-protected nanoparticles and maximizing the photoluminescence of metallic clusters through the exploitation of biologically relevant ligand properties.