Binding studies of the X-ray characterized [SnMe₂Cl₂(Me₂phen)] complex with human serum albumin: experimental and...

Due to the limitations of platinum-based chemotherapeutics such as cisplatin, including severe toxicity and acquired drug resistance, the development of alternative metal-based agents with improved efficacy and reduced side effects has become a key goal in medicinal chemistry. Among these, organotin(IV) compounds have attracted considerable interest owing to their potent antibacterial and anticancer properties. Since the pharmacological activity, transport, and bioavailability of such metal-based drugs are strongly influenced by their binding to plasma proteins particularly human serum albumin (HSA) understanding these interactions is essential for evaluating their in vivo behavior and therapeutic potential. This study investigates the binding behavior of the organotin(IV) complex [SnMe₂Cl₂(Me₂phen)] with HSA under physiological pH (7.4), utilizing both spectroscopic techniques and molecular docking studies. Upon addition of the complex, a decrease in HSA absorbance was observed, suggesting an interaction between the complex and the protein. Fluorescence quenching data, along with the calculated Stern-Volmer (K_sv) and bimolecular quenching (k_q) constants, indicated a static quenching mechanism. Thermodynamic parameters (ΔH° < 0 and ΔS° < 0) implied that hydrogen bonding forces and van der Waals forces predominantly govern the binding process. Site-selective displacement assays with site-specific markers, warfarin and ibuprofen, suggested that the complex may associate with both Sudlow's site I and site II of HSA. Circular dichroism (CD) spectroscopy revealed a reduction in the α-helical content of HSA upon complexation, indicating partial conformational changes in the protein structure. Molecular docking results supported the experimental findings and provided further insight into the binding mode of the complex with HSA.