Platinum(IV) Complexes Featuring Axial (1, 4–13C2)Succinato Ligands – Synthesis, Characterization, and Preliminary ­Investigations in Cancer Cell Lysates

Abstract

AbstractThe chemistry of cytotoxic platinum(II) complexes is more or less restricted to ligand exchange reactions, derivatization of coordinated ligands is cumbersome, and subsequent purification in many cases impossible. Consequently, kinetically more inert platinum(IV) complexes found their way into the development of novel, promising anticancer drugs. Research has focused more and more during the last years on the use of platinum(IV) complexes featuring one or two axial succinato ligands in which one carboxylic acid moiety is available for further derivatization. In order to gain a deeper insight into the mechanism of action, isotopically labeled platinum(IV) complexes with axial (1, 4–13C2)succinato ligands were synthesized and fully characterized by multinuclear (1H, 13C, 15N, and 195Pt) 1D‐ and 2D‐NMR spectroscopy. Especially of note in this context is a long range 1H,13C shift correlation signal detected between the equatorial ammine protons and the axially coordinated carboxylato moiety. Furthermore, their behavior in extracts of SW480 cancer cells was investigated. Preliminary results demonstrate that cisplatin analogs are reduced significantly faster in comparison to carboplatin analogs.