Unraveling site-specific dopant behavior governing antibacterial activity in doped titanate nanosheets

Antimicrobial resistance (AMR) poses a critical global health threat, particularly for immuno-compromised patients, such as those undergoing treatment for hematological malignancies. To address the limitations of conventional antibiotics, two-dimensional (2D) inorganic nanomaterials have attracted increasing attention as alternative antimicrobial platforms owing to their tunable surface chemistry and mechanical rigidity. In this study, we investigated the antibacterial mechanisms of copper- or silver-doped titanate nanosheets (Cu-TNS and Ag-TNS), focusing on how the dopant species and their structural locations influence antibacterial activity. Fine titanate nanosheets with low aspect ratios were synthesized through a liquid-phase reaction, enabling the evaluation of the chemical contributions of trace metal dopants while minimizing nanosheet-induced mechanical killing effects, as reported previously. Comprehensive characterization, including Raman spectroscopy, DLS, and XPS, indicated that Cu⁺ ions were substitutionally incorporated into the titanate lattice, generating oxygen vacancies and modulating the electronic structure, whereas Ag⁺ ions are suggested to reside in the interlayer galleries as exchangeable cations. Antibacterial assays against Staphylococcus aureus and Escherichia coli demonstrated that Cu-TNS exerted stable, contact-dependent antibacterial effects without ion diffusion, whereas Ag-TNS exhibited strong but transient activity driven by Ag⁺ release, which was consistent with the inhibition-zone formation observed in disk diffusion tests. Overall, Ag-TNS is suited for short-term, high-intensity disinfection, whereas Cu-TNS provides stable, contact-dependent surface antibacterial properties ideal for solid-state applications, such as antimicrobial coatings. This study provides the first systematic elucidation of metal-dependent antibacterial mechanisms from a chemical perspective and highlights design principles for next-generation inorganic antimicrobial materials.