ESIPT promotion or inhibition: gold cluster orientation in alanine.

An orientation-dependent regulatory mechanism whereby gold (Au) clusters influence the excited-state intramolecular proton transfer (ESIPT) process in biomolecules is revealed for the first time in this study. Using alanine (ALA) as a model system with multiscale theoretical calculations, we reveal that the orientation of Au clusters can precisely modulate both the reaction pathway and thermodynamic feasibility of proton transfer. Theoretical screening of clusters with different numbers of Au atoms and excited-state dynamics studies indicate that pristine ALA hardly undergoes spontaneous proton transfer in the excited state; however, upon sulfurization and bonding with clusters, ESIPT is activated. IR and Raman vibrational analyses demonstrate that the alanine-Au5 cluster (ALA-Au5) exhibits the most significant intramolecular hydrogen bond regulatory effect and achieves an optimal balance between capturing orientation-specific vibrational features and maintaining computational efficiency. A machine learning-assisted conformational search identified stable configurations, which lay a foundation for subsequent calculations. Electronic structure and energy analyses confirm that Au cluster binding to the acceptor blocks ESIPT while binding to the donor boosts it, elucidating how the spatial orientation of metal clusters modulates electronic structure and excited-state dynamics and providing a theoretical foundation for the rational design of metal-bio hybrid photofunctional systems.