Rhodium(III) in a cage of the 1,3-propanediamine-N,N,N′-triacetate chelate: X-ray structure, solution equilibria, computational study and biological behavior

Two new octahedral Rh(III) complexes that are potential chemotherapeutic agents have been synthesized from the 1,3-propanediamine-N,N,N’-triacetate ligand (1,3-pd3a): [Rh(1,3-pd3a)(H2O)]·2H2O (1) and Na[Rh(1,3-pd3a)Cl]·2H2O (2). Both complexes were characterized by IR, UV–Vis and NMR spectroscopy, as well as elemental analysis. Only the structure of 2 was determined by a single crystal X-ray diffraction study. The asymmetric unit contains the negatively charged rhodium complex, a sodium ion and two water molecules. The positions of the carboxylate groups define the cis-polar geometry. DFT calculations on 1 and 2 have also been done to confirm experimental results. In order to determine the protonation constants of 1,3-H3pd3a, stability constants and the stoichiometry of the complexes in aqueous solution, pH-potentiometry and UV–Vis spectrophotometry were used. Docking of 1 to human serum albumin (HSA) gives the reasonable assumption that this complex can be easily transported to the target cells. The complexes, as well as the 1,3-pd3a and ed3a ligands, were tested against various cancer and one normal human cell lines. Complex 2 and both ligands display significant cytotoxicity against the HeLa cancer cell line, while 1 shows good antitumor activity against MCF-7. Flow cytometry analysis showed the apoptotic death of the cells with cell cycle arrest in the G2/M phase (Na[Rh(1,3-pd3a)Cl]·2H2O) and G0/G1 phase (1,3-pd3a).