Plecstatin-1 ([RuCl(p-cym)(pca)]Cl; p-cym = p-cymene, pca = (4-fluorophenyl-2-pyridinecarbothioamide)) is an organometallic anticancer compound of the ruthenium “piano-stool”/”half-sandwich” class which displays promising pre-clinical results owing to its novel mode of action which involves targeting plectin units in the cytoskeleton to inhibit cancer cell motility. X-ray fluorescence microscopy of single SKOV3 cells treated with plecstatin and its Os and Ir analogues clearly shows that the cellular distribution of the three metals is alike. This suggests that the coordination of the three complexes is mostly unchanged in cells, as the diverse chemistry of the metals would presumably result in distinct cellular distributions if they were liberated from the original ligand sphere. We have used EXAFS of plecstatin incubated in water, culture media, and human blood to rationalise the similar cell distributions, by showing that the p-cym and pca ligands remain coordinated. Intriguingly, NMR and other data reveal dimerisation of the complex over several hours in water, but this is not evident in EXAFS of the blood sample.
I will contrast this last observation with a similar EXAFS study on related Ru and Rh piano-stool complexes with 8-aminoquinoline ligands in place of the pca, where the analysis is sensitive to, and shows variation in, the stability and formation of the relevant dimers in whole human blood.