Phototoxicity of Half-Sandwich Rhodium(III) Complexes with Anthracene and Biphenyl Substituents toward Mammalian Cancer Cells and Multicellular Tumor Spheroids

We report the synthesis and characterization of three
half-sandwich
rhodium(III) complexes incorporating anthracene and biphenyl moieties
to investigate their photobiological activity. Complexes 1 and 2, bearing anthracene-based Schiff base ligand,
displayed pronounced phototoxicity upon blue-light irradiation, with
complex 2 achieving a phototoxicity index of 144 in A375
melanoma cells. In contrast, complex 3, lacking the anthracene
unit, was photoinactive. Photoactivation of complexes 1 and 2 induced −NCH– Schiff bond
cleavage, releasing anthracene-9-carbaldehyde, as confirmed by UV–vis
and mass spectrometry. Blue light also enabled catalytic oxidation
of NADH to NAD+. Mechanistic studies revealed oncosis-like
cell death mediated by reactive oxygen species. Both complexes retained
activity in 3D tumor spheroids, demonstrating efficient tissue penetration.
These results identify anthracene-functionalized rhodium(III) complexes
as promising candidates for photodynamic therapy and provide, to our
knowledge, the first detailed mechanistic insight into photopotentiation
in half-sandwich rhodium systems.