5-Hydroxyisophthalic acid and neocuproine containing copper(II) complex as a promising cytotoxic agent: Structure elucidation, topology, Hirshfeld surface, DFT calculations, and molecular docking analysis

Abstract

We aimed to synthesize a new copper(II) complex, namely [Cu(H2IPA)(NC)(Cl)]⋅H2O (1) (where, H3IPA = 5-hydroxy isophthalic acid and NC = 2,9-dimethyl-1,10-phenanthroline or Neocuproine) as a promising chemotherapeutic agent. Complex 1 was structurally characterized by single-crystal X-ray diffraction (SCXRD), UV-Visible, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and powder X-ray diffraction (PXRD) methods. Single crystal diffraction analysis reveals that Cu(II) ion exists in a distorted square pyramidal geometry, with the ligation of a chloride ion, two oxygen atoms, and two nitrogen atoms. Topological structural simplification of complex 1 shows ins as an underlying net. The prominent intermolecular interactions and their quantitative contributions in complex 1 were investigated using Hirshfeld Surface (HS) analysis. The DFT calculations were also performed to validate the experimental results (XRD, FTIR, and UV-Visible). In vitro cytotoxicity of complex 1 was performed against acute myeloid leukemia (THP-1), colorectal (SW480), and prostate cancer (PC-3) cell lines by utilizing MTT assay. The result shows that complex 1 has the ability to inhibit the growth of cancer cells at a lower concentration. The morphological changes that occur during apoptosis were carried out with acridine orange/ethidium bromide (AO/EB) staining methods on THP-1 and SW480 cancer cell lines. Additionally, comprehensive molecular docking studies were performed to understand the potential binding interactions of complex 1 with target protein and DNA double helix.