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 pK_a 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.