Cancer is one of the main causes of death worldwide. Chemotherapy, despite its severe
side effects, is to date one of the leading strategies against cancer. Metal-based drugs
present several potential advantages when compared to organic ones and gained trust
from the scientific community after the approval on the market of the drug cisplatin.
Recently, we reported a ruthenium complex ([Ru(DIP)2(sq)](PF6), where DIP is 4,7-
diphenyl-1,10-phenantroline and sq is the semiquinonate), with a remarkable potential
as chemotherapeutic agent against cancer, both in vitro and in vivo. In this work, we
analyse a structurally similar compound, namely [Ru(DIP)2(mal)](PF6), carrying the
flavour-enhancing agent approved by the FDA, maltol (mal). To possess an FDA
approved ligand is crucial for a complex, whose mechanism of action might include
ligand exchange. Herein, we describe the synthesis and characterisation of
[Ru(DIP)2(mal)](PF6), its stability in solutions and in conditions which resemble the
physiological ones, and its in-depth biological investigation. Cytotoxicity tests on
different cell lines in 2D model and on HeLa MultiCellular Tumour Spheroids (MCTS)
demonstrated that our compound has higher activity compared to the approved drug
cisplatin, inspiring further tests. [Ru(DIP)2(mal)](PF6) was efficiently internalised by
HeLa cells through a passive transport mechanism and severely affected the
mitochondrial metabolism. <br>
Photoinduced Ligand Exchange Dynamics of a Polypyridyl Ruthenium Complex in Aqueous Solution