Two thermally activated ruthenium(II) polypyridyl complexes, cis-Ru(bpy)₂Cl₂ and trans-Ru(qpy)Cl₂ were investigated to determine the impact of the geometric arrangement of the exchangable ligands on the potential of the compounds to act as chemotherapeutics. In contrast to the geometry requirements for cisplatin, trans-Ru(qpy)Cl₂ was 7.1–9.5× more cytotoxic than cis-Ru(bpy)₂Cl₂. This discovery could open up a new area of metal-based chemotherapeutic research.