Synthesis and Photobiological Activity of Ru(II) Dyads Derived from Pyrrole-2-carboxylate Thionoesters

The
synthesis and characterization of a series of heteroleptic ruthenium­(II)
dyads derived from pyrrole-2-carboxylate thionoesters are reported.
Ligands bearing a conjugated thiocarbonyl group were found to be more
reactive toward Ru­(II) complexation compared to analogous all-oxygen
pyrrole-2-carboxylate esters, and salient features of the resulting
complexes were determined using X-ray crystallography, electronic
absorption, and NMR spectroscopy. Selected complexes were evaluated
for their potential in photobiological applications, whereupon all
compounds demonstrated in vitro photodynamic therapy effects in HL-60
and SK-MEL-28 cells, with low nanomolar activities observed, and exhibited
some of the largest photocytotoxicity indices to date (>2000).
Importantly, the Ru­(II) dyads could be activated by relatively soft
doses of visible (100 J cm–2, 29 mW cm–2) or red light (100 J cm–2, 34 mW cm–2), which is compatible with therapeutic applications. Some compounds
even demonstrated up to five-fold selectivity for malignant cells
over noncancerous cells. These complexes were also shown to photocleave,
and in some cases unwind, DNA in cell-free experiments. Thus, this
new class of Ru­(II) dyads has the capacity to interact with and damage
biological macromolecules in the cell, making them attractive agents
for photodynamic therapy.