Photoresponsive Ru Complex–Gold Nanoparticle Hybrids for Theranostics: A Theoretical Study of Electronic Structure and Luminescence-Based Detection

Photoactivatable nitric oxide donors (photoNORMs) are promising agents for controlled NO release and real-time optical tracking in biomedical theranostics. Here, we report a comprehensive density functional theory (DFT) and time-dependent DFT (TDDFT) study on a series of hybrid ruthenium-gold nanocluster systems of the general formula [(L)Ru(NO)(SH)@Au₂₀], where L = salen, bpb, porphyrin, or phthalocyanine. Structural and bonding analyses reveal that the Ru-NO bond maintains a formal {RuNO}⁶ configuration with pronounced Ru → π*(NO) backbonding, leading to partial reduction of the NO ligand and an elongated N-O bond. Natural Bond Orbital (NBO), Natural Energy Decomposition Analysis (NEDA), and Extended Transition State-Natural Orbitals for Chemical Valence (ETS-NOCV) analyses confirm that Ru-NO bonding is dominated by charge-transfer and polarization components, while Ru-S and Au-S linkages exhibit a delocalized, donor-acceptor character coupling the molecular chromophore with the metallic cluster. TDDFT results reproduce visible-near-infrared (NIR) absorption features arising from mixed metal-to-ligand and cluster-mediated charge-transfer transitions. The calculated zero-zero transition and reorganization energies predict NIR-II emission (1.8-3.8 μm), a region of high biomedical transparency, making these systems ideal candidates for luminescence-based NO sensing and therapy. This study establishes fundamental design principles for next-generation Ru-based photoNORMs integrated with plasmonic gold nanoclusters, highlighting their potential as multifunctional, optically trackable theranostic platforms.