The present work investigates the surface chemistry engineering of Cu-based metal¿organic frameworks (MOFs) and the influence of amine and sulfonic functionalities on their structural, electronic, and antibacterial properties. Cu-BDC, Cu-BDC-NH¿, and Cu-BDC-SO¿H were synthesized via solvothermal synthesis and post-synthetic modification. FTIR and XPS analyses confirmed changes in the local chemical environment associated with Cu¿ligand coordination and the incorporation of amine- and sulfonic-related functionalities, while XRD and SEM/EDS revealed functionalization-dependent changes in crystal structure, morphology, and elemental composition. Periodic density functional theory (DFT) calculations provided complementary insights into the effects of functionalization on framework energetics and the electronic environment of the Cu centers. Antibacterial assays against Escherichia coli and Staphylococcus aureus demonstrated strong antibacterial activity for all Cu-based MOFs. Pristine Cu-BDC exhibited the strongest overall bactericidal performance and the highest electroactive Cu availability, whereas the functionalized materials showed more controlled time-dependent Cu availability. Notably, Cu-BDC-SO¿H exhibited greater antibacterial activity than Cu-BDC-NH¿, despite its lower electroactive Cu availability, indicating that antibacterial performance cannot be explained solely by Cu availability and is also influenced by the chemical environment of surface functionalization. Overall, the integration of structural characterization, electrochemical analysis, antibacterial assays, and DFT calculations establishes a qualitative structure¿electronic-property¿activity relationship, demonstrating that functional-group engineering is an effective strategy for tuning Cu availability and antibacterial performance in Cu-MOFs. These findings provide a basis for the rational design of functionalized Cu-MOF platforms with adjustable antibacterial activity profiles for future antimicrobial applications.
