X-ray fluorescence microscopy and X-ray absorption spectroscopy reveal the stability of the plecstatin-1 scaffold in biological model systems: comparison of Ru, Os and Ir analogues

Abstract

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. Its mode of action is ascribed to targeting plectin in the cytoskeleton to inhibit cancer cell motility. In this research, we report X-ray fluorescence microscopy (XFM) data demonstrating that the cellular distributions of the metals from the Os and Ir analogues of plecstatin-1 are identical to that of Ru in SKOV-3 ovarian cancer cells treated with plecstatin-1. Extended X-ray absorption fine structure (EXAFS) spectroscopy data confirms that both the p-cym, and the ancillary pca ligand, remain coordinated after incubation of plecstatin-1 in cell media (in the presence or absence of foetal bovine serum), or, in whole human blood, with the likely ligand substitution of the chlorido ligand for a thiol when available. The apparent stability of the complex scaffold to challenge from a wide variety of biological ligands can be used to rationalise the similar cell targeting behaviour of the Ru, Os and Ir complexes.