Synthesis, Characterization, and Density Functional Theory Modeling of New Cu‐ and Zn‐Based Cysteine and Glutamic Acid Nanocomplexes as Anticancer Agents

ABSTRACT In this study, bulk and nanoscale ternary complexes, [(Cu)(Cys)(Glu)(H 2 O) 2 ]·H 2 O and [(Zn)(Cys)(Glu)(H 2 O) 2 ]·2H 2 O, were synthesized using cetyltrimethylammonium bromide (CTAB) as a capping agent for nanoscale structure formation. Characterization via electronic spectroscopy, magnetic susceptibility, transmission electron microscopy, UV‐visible spectroscopy, thermogravimetric analysis, Fourier transform infrared (FTIR) spectroscopy, and mass spectrometry confirmed Cys coordination through amino and carboxylate groups, leaving the thiol moiety free. At the same time, Glu coordinated via amino and carboxylate groups, with one carboxylic group unbound. FTIR analysis further validated CTAB binding to functional groups. The nanosized complexes exhibited selective antiproliferative and proapoptotic effects against hepatocellular carcinoma (HepG2) cells, with lower IC 50 values than 5‐fluorouracil. Density functional theory (DFT) calculations (B3LYP/6‐311G(d,p) and LANL2DZ levels) supported experimental findings, with natural bond orbital analysis revealing bond strength, charge transfer, and molecular stability. Antibacterial assays showed efficacy against specific bacterial strains. Molecular docking and FTIR analyses suggested strong binding affinity to the human coronavirus NL63 nucleocapsid protein (PDB ID: 5EPW), with predicted harmonic vibrations elucidating potential inhibitory mechanisms against coronavirus disease 2019 (COVID‐19).