Exploring the Potential of a New Nickel(II):Phenanthroline Complex with L-isoleucine as an Antitumor Agent: Design, Crystal Structure, Spectroscopic Characterization, and Theoretical Insights.

This study presents the synthesis, physicochemical characterization, and biological evaluation of a novel ternary nickel(II) complex with isoleucine and 1,10-phenanthroline ligands, [Ni(Phen)(Ile)(2)]∙6H(2)O, designed as a potential antitumor agent. Single-crystal X-ray diffraction revealed a monoclinic structure (C2-space group) with an octahedral Ni(II) coordination involving Phen and Ile ligands. A Hirshfeld surface analysis highlighted intermolecular interactions stabilizing the crystal lattice, with hydrogen bonds (H···H and O···H/H···O) dominating (99.1% of contacts). Density functional theory (DFT) calculations, including solvation effects (in water and methanol), demonstrated strong agreement with the experimental geometric parameters and revealed higher affinity to the water solvent. The electronic properties of the complex, such as HOMO-LUMO gaps (3.20-4.26 eV) and electrophilicity (4.54-5.88 eV), indicated a charge-transfer potential suitable for biological applications through interactions with biomolecules. Raman and infrared spectroscopic studies showed vibrational modes associated with Ni-N/O bonds and ligand-specific deformations, with solvation-induced shifts observed. A study using ultraviolet-visible-near-infrared absorption spectroscopy demonstrated that the complex remains stable in solution. In vitro cytotoxicity assays against MCF-7 (breast adenocarcinoma) and HCT-116 (colorectal carcinoma) cells showed dose-dependent activity, achieving 47.6% and 65.3% viability reduction at 100 μM (48 h), respectively, with lower toxicity to non-tumor lung fibroblasts (GM07492A, 39.8%). Supporting the experimental data, we performed computational modeling to examine the pharmacokinetic profile, with particular focus on the absorption, distribution, metabolism, and excretion properties and drug-likeness potential.