The aqueous stability and interactions of organoruthenium compounds with serum proteins, cell culture medium, and human serum

Metal complexes bind to a wide variety of biomolecules and the control of the reactivity is essential when designing anticancer metallodrugs with a specific mode of action in mind. In this study, we used the highly cytotoxic compound [Ru(II)(cym)(8-HQ)Cl] (cym = η(6)-p-cymene, 8-HQ = 8-hydroxyquinoline), the more inert derivative [Ru(II)(cym)(8-HQ)(PTA)](SO(3)CF(3)) (PTA = 1,3,5-triaza-7-phosphaadamantane), and [Ru(II)(cym)(PCA)Cl]Cl (PCA = pyridinecarbothioamide) as a complex with a different coordination environment about the Ru center and investigated their stability, interactions with proteins, and behavior in medium (αMEM) and human serum by capillary zone electrophoresis. The developed method was found to be robust and provides a quick and low-cost technique to monitor the interactions of such complexes with biomolecules. Each complex was found to behave very differently, emphasizing the importance of the choice of ligands and demonstrating the applicability of the developed method. Additionally, the human serum albumin binding site preference of [Ru(II)(cym)(8-HQ)Cl] was investigated through displacement studies, revealing that the compound was able to bind to both sites I and site II, and the type of adducts formed with transferrin was determined by mass spectrometry.