Elucidation of DNA binding interaction of new Cu(II)/Zn(II) complexes derived from Schiff base and L-tryptophan amino acid: a multispectroscopic and molecular docking approach

Herein, we describe the synthesis, structural elucidation, and DNA interaction of newly synthesized Cu(II) and Zn(II) complexes, i.e., [Cu(SB)(L-trp)(H₂O)₂]NO₃ (1) and [Zn(SB)(L-trp)(H₂O)₂]NO₃ (2) (SB = Schiff base obtained from the reaction between o-vanillin and 2-amino-2-methylpropane-1,3-diol; L-trp = L-tryptophan). From the analysis, a six-coordinated environment around the Cu(II) or Zn(II) center is proposed. The ability of the complexes to bind with calf thymus DNA was examined by optical spectroscopy (UV-vis titrations and steady-state fluorescence emission) and viscosity measurements. The vivid experimental results revealed that complexes 1 and 2 avidly bind to DNA through surface and groove binding modes, albeit with dissimilar intrinsic binding constants (1.54 × 10⁴ and 1.36 × 10⁴ M^-1 for 1 and 2, respectively). Both complexes can displace ethidium bromide (EB) to some extent from the intercalated EB-DNA system, resulting in fluorescence quenching. Additional experiments such as [Fe(CN)₆]^4--induced quenching and thermal melting confirmed the electrostatic and groove binding mode. Furthermore, molecular docking studies verified that both complexes locate in the DNA minor groove by surface binding and were stabilized through weak intermolecular forces. The binding affinity of the lowest energy docked pose was found to be -5.37 kcal/mol for complex 1 and - 5.18 kcal/mol for complex 2. The present work is expected to pave the way for the synthesis of DNA-targeting Cu(II)/Zn(II) metal complexes for the development of chemotherapeutic agents.