Synthesis, structural characterisation and solution chemistry of ruthenium(III) triazole-thiadiazine complexes

Two ruthenium(III) complexes structurally similar to the anticancer compound NAMI were prepared: Na[RuCl₄(DMSO)(L1)] (1) and Na[RuCl ₄(DMSO)(L2)] (2), where L1 and L2 are differently functionalised triazole-thiadiazine ligands. To facilitate the crystallisation of the complex anions, Na⁺ was substituted with the [bis(triphenylphosphoranylidene) ammonium] cation (PPN⁺), allowing the X-ray characterisation of PPN[RuCl₄(DMSO)(L1)]·2H₂O (1a·2H ₂O) and PPN[RuCl₄(DMSO)(L2)]·3H₂O (2a·3H₂O), respectively. The two compounds undergo stepwise hydrolytic processes, as assessed by means of UV-vis and ¹H NMR spectroscopy. The first hydrolytic step consists of the replacement of a chloride anion with a water molecule, with a half-life of 50 min (1) and 110 min (2), while the subsequent hydrolytic steps are more complicated to describe since more than one product is generated at the same time. The redox potential of the Ru(III)/Ru(II) couple (0.31 V for 1 and 0.28 V for 2) suggests that these complexes can be reduced in the intracellular environment, in agreement with the "activation by reduction" mechanism proposed for NAMI and NAMI-A. 1 and 2 were tested on a human cancer cell line derived from a fibrosarcoma (HT1080), and on non-cancerous primary human fibroblasts (HF), where they showed a modest inhibitory effect.