Abstract / Summary
This review presents a systematic evaluation of the synthesis, structural characterization, and pharmacological applications of 66 Zn(II) Schiff base complexes. Although platinum-based chemotherapeutics remain clinically vital, their efficacy is limited by dose-limiting toxicity and acquired drug resistance. Zn(II) complexes offer an alternative because of their excellent biocompatibility and d10 structural plasticity. Herein, we analyze key correlations among ligand structure, coordination geometry, spectroscopic data (FT-IR, NMR, and UV–Vis), and biological efficacy across these 66 complexes. Structural analysis shows that chelation reduces metal ion polarity and increases complex lipophilicity. Comparative analysis indicates that hexacoordinate complexes with octahedral geometry exhibit the highest therapeutic potency, as evidenced by exceptional IC 50 values against MCF-7 breast cancer cells. This elevated apoptotic activity is driven by geometric distortions that optimize hydrogen bonding and enable highly targeted DNA minor-groove binding. By mapping these comprehensive structure–activity relationships (SAR) across tetrahedral, pentacoordinate, and octahedral configurations, this review establishes a strategic framework for the rational design of non-platinum metallodrugs with optimized safety profiles and targeted cytotoxicity. These findings are further corroborated by state-of-the-art computational insights, focusing on molecular docking parameters and binding affinity constants ( K b ) for selected complexes.