Octahedral [(8-quinolinyl/phenanthridinyl)amine)Ga(III)] complexes, reactivity, affinity for biomolecules, anti-cancer and computational evaluations

Abstract

Abstract Octahedral iodo gallium(III) complexes, GaL1-L3(SN)I, incorporating bis-(azaaryl)amine ligands (L1–L3) with varying conformational flexibility, were synthesized and characterized by spectroscopic and elemental analyses to evaluate ligand effects on reactivity and affinity for biological targets. Iodide substitution by biologically relevant nucleophiles (guanine and thiourea), monitored spectrophotometrically, revealed ligand-dependent rates, with the fastest substitution observed for the dicationic GaL1(SN)I bearing the most compact and flexible ligand (L1), compared to the more rigid monocationic L2 and L3 analogues. UV–Visible studies of interactions with bovine serum albumin and calf thymus DNA indicated moderate to strong binding ( K b ≈ 10 4 M⁻ 1 ), with affinities decreasing in the order GaL1(SN)I > GaL2(SN)I > GaL3(SN)I. Competitive binding assays, supported by molecular docking, suggested bimodal binding modes involving moderate groove binding and partial intercalation. Density functional theory calculations demonstrated that trends in structural parameters and electronic reactivity descriptors were consistent with experimentally observed iodide substitution rates and biomolecular binding affinities. Cytotoxicity evaluation of L1–L3 and GaL1-L3(SN)I against selected human cancer and non-malignant cell lines demonstrated moderate antiproliferative activity. Notably, L1 and GaL1(SN)I exhibited enhanced inhibition comparable to cisplatin against HeLa cervical cancer cells, highlighting their therapeutic potential. The data provided insights into the structural-activity relationships governing the reactivity and anticancer activity of Ga(III) complexes bearing N ∧ N ∧ N and thiosemicarbazide chelators.