Design, Synthesis, DFT, and Biological Evaluation of Nano-Sized Pt(II) and Cu(II) Complexes of 2-(Benzo[d]oxazol-2-yl)phenylphosphoramidic Dichloride: Spectral Analysis, Cell Cycle Arrest, Apoptosis Assay, Cytotoxicity, and DNA Binding/Cleavage

A new novel bidentate benzo[d]oxazole ligand, 2-((benzo[d]oxazol-2-yl)phenyl)phosphoramidic dichloride (H-BOPPADC), is synthesized through reacting 2-(benzo[d]oxazol-2-yl)aniline and phosphoryl trichloride in a 1:1 ratio. Nano-sized bivalent metal complexes are created and subsequently characterized using various physical methods. Based on the elemental analysis results, the complexes are inferred to follow the overall formula [M(BOPPADC)Cl(H₂O)]·nH₂O (as M = Cu(II) (S1); n = 6 and Pt(II) (S2); n = 3 and BOPPADC = ligand). The molar conductance findings demonstrate the nonelectrolytic behavior of all inspected metal complexes. Infrared spectral analysis indicates both the removal of a proton and the bonding of the imine-NH. Additionally, it supports involving the nitrogen atom from the benzo[d]oxazol group in complex development. Quantum chemical calculations, along with electronic spectra and magnetic susceptibility findings, indicate that two complexes exhibit a square planar configuration. The EPR spectrum for Cu(II) complex confirmed the suggested structure. Thermodynamic parameters are determined through the Horowitz–Metzger (HM) and Coast–Redfern (CR) techniques. The complexes' structural geometries are validated by employing the DFT approach, utilizing DMOL³ determinations. The EDX, TEM, and AFM analysis of the studied complex unveils distinct and strong diffraction peaks, indicating its crystalline nature and providing evidence of its nano-sized particle sizes. Various bacterial and fungal pathogens were evaluated to assess the in vitro antimicrobial effectiveness of the ligand and metal complexes. The results highlight these compounds as a highly effective fungicides and bactericides. To explore the interaction among CT-DNA and M(II) complex, absorption titration was performed within a Tris-HCl buffer (pH 7). Additionally, viscosity measurement was used to evaluate the DNA-binding activity of the Pt(II) complex in a buffer solution. The data demonstrated that Pt(II) complex exhibits strong binding to CT-DNA through an intercalative binding mechanism. The capability of the complexes S1 and S2 to cleave DNA without the need for external agents is demonstrated by their interaction with pUC19 DNA. In vitro cytotoxic effects of the formulated complexes were explored utilizing HePG2 liver cancer cells. According to IC₅₀ and selective index (SI) measurements, it was shown that the complex exhibited higher potency against MCF7 cell lines. Moreover, Pt(II) complex exhibited the capability of triggering DNA damage in HePG2 cells, resulting in dose-dependent cell apoptosis. Subsequent investigations revealed that the complex triggered cell cycle arrest during the S and G2 phases.