Synthesis, Characterization, and Multimodal DNA Interaction of Novel Mn(II), Fe(III), and Co(II) Acylhydrazone Complexes

ABSTRACT A novel acylhydrazone Schiff base ligand was synthesized via the condensation of 2‐fluorobenzohydrazide with (2E)‐3‐(2‐methoxyphenyl)prop‐2‐enal and subsequently complexed with Mn(II), Fe(III), and Co(II) ions. We primarily characterized the resulting materials by thermal analysis (TGA‐DSC), elemental analysis, high‐resolution electrospray ionization mass spectrometry (HRESIMS), and powder x‐ray diffraction (PXRD), complemented by FT‐IR and UV–vis spectroscopy, 1 H NMR, and complexometric titration, confirming the formation of stable, well‐defined coordination structures. DNA‐binding studies using absorption spectroscopy, viscosity measurements, and ethidium bromide displacement assays supported compound‐dependent, predominantly groove‐associated or mixed non‐covalent interactions rather than a classical intercalative binding mode. Fluorescence quenching and binding assays with bovine serum albumin (BSA) demonstrated measurable protein‐binding affinities, with the Fe(III) complex showing the highest experimental binding constant. Molecular docking complemented the experimental findings by suggesting distinct binding orientations and non‐covalent interaction patterns with DNA and BSA. For DNA, the predicted interactions included hydrogen bonding, halogen contacts, and π‐related interactions with nucleotides, whereas BSA docking suggested a probable binding region in the vicinity of Site II. The compounds also showed positive log P values, indicating a moderate lipophilic character. Collectively, the results demonstrate that metal coordination modulates DNA and BSA recognition, providing complementary insight into the structure–interaction relationships of these acylhydrazone complexes.