Antimicrobial and DNA Binding Activity of Some Metalloantibiotic Ternary Chelates Synthesized via Green Ball Milling Method, Characterization, SAR, and Drug-Likeness Prediction

Novel metalloantibiotic ternary complexes are created by combining cefazolin (CFZ) with sulfate salts of Cu²⁺, Zn²⁺, and VO²⁺ using a ball milling technique. This method is waste-free and minimizes hazardous materials while achieving a high yield of 98% in a few minutes. The structure of the synthesized metalloantibiotic complexes is characterized through elemental analysis, FTIR, UV–visible spectroscopy, TEM, SEM, EDX, and powder XRD. According to the results, CFZ acted as a neutral bidentate ligand by binding to (C=O)_lactam and (C=O)_amide. Also, as shown by the ESR, magnetic, and UV–visible data, Cu²⁺ has tetragonally deformed octahedral geometry, whereas VO²⁺ has a square pyramidal geometry. Moreover, the optimized molecular structures as well as some quantum mechanical parameters of CFZ and its metalloantibiotic complexes are estimated using DFT theory. The antimicrobial activity of CFZ and its metalloantibiotic complexes is evaluated against Staphylococcus aureus (a gram-positive bacterium), Escherichia coli (a gram-negative bacterium), and Candida albicans (a fungus). As indicated by the outcome data of all the isolated complexes examined, the Zn² complex has the strongest antibacterial and antifungal activity. To further explore, the DNA binding activity is performed using methyl green dye that acted as a substrate for detecting deoxyribonucleases. The CFZ ligand exhibited the strongest DNA binding, with an IC₅₀ value below the standard (27.21), followed by the Zn²⁺ complex (30.50). The VO²⁺ complex demonstrated moderate DNA binding with an IC₅₀ of 54.19, while the Cu²⁺ complex showed weak DNA binding activity (89.26).