Critical factors affecting the albumin binding of half-sandwich Ru(ii) and Rh(iii) complexes of 8-hydroxyquinolines and oligopyridines

Abstract

There is significant interest today in the interaction of half-sandwich anticancer organometallic complexes with proteins. It is considered as a crucial factor in the transport and mode of action of these compounds; thus it can affect their overall pharmacological and toxicological profiles. Albumin binding of high stability Ru(II)(η⁶-p-cymene) and Rh(III)(η⁵-C₅Me₅) complexes formed with 8-hydroxyquinoline, its 5-chloro-7-((proline-1-yl)methyl) substituted derivative, 2,2′-bipyridine and 1,10-phenanthroline is discussed herein. The interaction with human serum albumin in terms of kinetic aspects, binding strength and possible binding sites was studied in detail by means of various methods such as ¹H NMR spectroscopy, UV–visible spectrophotometry, steady-state and time-resolved fluorometry, ultrafiltration and capillary zone electrophoresis. Ru(II)(η⁶-p-cymene)(2,2′-bipyridine) and Ru(II)(η⁶-p-cymene)(1,10-phenanthroline) complexes do not bind to the protein measurably, most probably due to kinetic reasons. However, other complexes bind significantly to albumin with fairly different kinetics to albumin. The binding affinity towards hydrophobic binding pockets shows correlation with lipophilicity along with the actual charge of the respective complexes. The studied complexes preserve their original structure upon interaction with albumin. Formation constants computed for the binding of these metal complexes to histidine-containing model oligopeptides demonstrated significant ternary complex formation, pointing out the importance of histidine coordination in the binding of these types of complexes.