Unveiling the Bio-Interface via Spectroscopic and Computational Studies of (Propyl-3-ol/butyl-4-ol)triphenyltin(IV)...

Two structurally tunable (propyl-3-ol)triphenyltin(IV) (Ph₃SnL₁) and (butyl-4-ol)triphenyltin(IV) (Ph₃SnL₂) compounds were investigated at the human serum transferrin (Tf) molecular interface to resolve how ligand architecture and protein metallation modulate organotin(IV) biocompound stability and lobe-selective binding. Steady-state fluorescence spectroscopy revealed efficient quenching of native Tf emission (λ_ex = 280 nm, 296-310 K, pH 7.4) without significant spectral displacement, indicating the predominant formation of non-fluorescent ground-state complexes. Calculated bimolecular quenching constants (K_q ~10¹² M^-1 s^-1) exceeded the diffusion-controlled aqueous limit, ruling out a collisional dynamic quenching mechanism and confirming static complexation as the principal origin of fluorescence suppression. Double-log binding analysis revealed moderate affinity (K_a ~10²-10³ M^-1) and an approximately single dominant binding event per protein (n ≈ 0.65-0.90). Temperature-dependent van't Hoff evaluation yielded positive ΔH° and ΔS° values, supporting a spontaneous, entropy-favored association process largely governed by hydrophobic and dispersion-type contributions, consistent with lipophilic organotin(IV) scaffold accommodation. Iron (Fe³⁺) loading of Tf markedly enhanced ligand engagement, especially for Ph₃SnL₁, evidencing that metallation-induced lobe closure reshapes pocket accessibility and local polarity relevant for organotin(IV) binding presentation rather than simply strengthening empirical docking scores. Molecular docking localized the most stable Ph₃SnL₂ poses in the sterically confined, rigid C-lobe, while Ph₃SnL₁ preferentially penetrated the more adaptive N-lobe. ONIOM QM/MM refinement of docking poses confirmed strong interfacial stabilization (ΔE_int ≈ -38 to -62 kcal mol^-1) and clarified charge-packing interplay without invoking frontier orbital analysis. The results map multiscale structure-interaction relationships defining lobe preference and complex stability at the transferrin interface.