Kanyora Amos Kimemia2026-01-222026-01-222025http://41.89.96.81:4000/handle/123456789/3386Cancer, a non-communicable disease, continues to rank among the top causes of mortality globally, with a substantial number of new diagnoses reported annually. Although platinum- based drugs are involved in nearly 50% of cancer treatment regimens and are highly effective against various types of cancer, they suffer from drawbacks that limit their broader application and efficacy. As altematives, (115-arene)ruthenium(II)/osmium(II) complexes have shown better antiproliferative properties and more favourable toxicity profiles, making them promising candidates for further exploration. This work reports the synthesis of fifteen mononuclear Ru(Il) and Os(II) complexes bearing 1]“-arene ligands in combination with either bis(pyrazol-l- yl)methane or pyrazolyl-pyridazine donor systems. Comprehensive characterization was carried out using a suite of techniques, including CHN elemental analysis, FTIR, UV—Vis spectroscopy, ‘H and "C NMR, mass spectrometry, and single-crystal X-ray diffraction. The electronic structures of the complexes were further examined through density functional theory (DFT) calculations. A subset of five Ru(II) pyrazolyl—pyridazine complexes was selected to probe their binding interactions with calf thymus DNA (CT-DNA) and glutathione (GSH) via UV—Vis absorption and fluorescence titration assays. The findings revealed that the Ru(II) compounds demonstrated moderate to strong affinities for CT-DNA, with binding occurring predominantly through minor groove interactions. Molecular docking studies further supported these findings, indicating stable binding conformations. The relative binding affinities were determined as follows: -5.8 kcal/mol (9) > -5.7 (4a) > -5.6 (3a) > -5.4 (3c) > -5.3 (4c) > -3.6 (cisplatin), suggesting stronger DNA binding than the standard drug cisplatin. Moderate anticancer activity was observed against the MCF-7 breast cancer cell line, with complex 9 being the most potent (IC50 = 41.94 i 2.05 uM), though none of the compounds showed efficacy against MDA-MB- 23l. Ru(II) complexes with bis(pyrazol-l-yl)methane ligands showed low cytotoxicity across all cell lines tested. DFT results indicated that electron density on the metal centre and surrounding ligands significantly influenced reactivity. GSH studies revealed that chloro analogues were more readily deactivated than iodo analogues. Collectively, the results indicate that these complexes hold promise as foundational structures for designing more effective anticancer therapeutics.enSynthesis of rutheniumCytotoxicity activityThesis