Polypyridyl coordinating ligands are common in metal complexes used in medicinal inorganic chemistry. Some of these ligands possess intrinsic cytotoxicity while others are biologically innocuous, and there is little information on the structure-activity relationships responsible for these disparities. Moreover, the mechanism(s) of action of the cytotoxic ligands are not clear, but ionophoric mechanisms seem likely. In order to provide new insights into the biological effects of bipyridyl type ligands and structurally related metal-binding systems, we have evaluated a large number of 2,2'-bipyridine and 1,10-phenanthroline ligands and their derivatives. Our studies demonstrate that there is no correlation between cytotoxicity IC<sub>50</sub> values and ligand properties such as pKa, log D, polarizability volume, and electron density. The binding affinities of the metal complexes for various endogenous metals, structural preferences, and reactivities will be discussed, along with mechanistic studies that elucidate the various effects on cellular function. The implications of this work extend beyond studies on either coordinating organic molecules that can act as ligands or photoejecting metal complexes, as the incorporation of some of these ligands into metal complexes assumed to be photochemically or thermally inert can result in significant, but artifactual, biological effects.

Is the metal center or the ligand the active species for photoejecting Ru(II) complexes?

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.