Ferrocenyl compounds show interesting antiproliferative properties. Consequently, ferrocene bearing moieties were prepared and coupled for the first time to anticancer platinum(IV) complexes. The compounds, featuring either one or two axially coordinated ferrocene-containing ligands, were fully characterized by ESI-MS and multinuclear ( 1 H, 13 C, 15 N, and 195 Pt) one-and two-dimensional NMR spectroscopy. 484Their cytotoxicity was investigated in three human cancer cell lines deriving from ovarian carcinoma (CH1), colon carcinoma (SW480), and non-small-cell lung carcinoma (A549) by means of the colorimetric MTT assay. Promising IC 50 values in the low micromolar range in CH1 and SW480 human cancer cells were found. www.eurjic.org FULL PAPER Scheme 1. Synthesis of ferrocene precursors L2-L6 and NMR numbering scheme. Scheme 2. Synthesis of complexes 3-5 and NMR numbering scheme. 486 www.eurjic.org FULL PAPER Scheme 3. Synthesis of platinum(IV) complexes 11-15 and NMR numbering scheme.As described in the literature, [16] novel Pt IV complexes with the Cl 2 N 2 O 2 coordination sphere show 195 Pt resonances in the region around 2656 ppm, whereas resonances for oxaliplatin-type platinum(IV) complexes appear in the region of 3230 ppm. As anticipated, the 195 Pt resonances are comparable for oxaliplatin-based Pt IV complexes 13, 14, and 15 with one acetato and one derivatized carboxylato ligand in the axial position to those for their biscarboxylated analogues. ESI-MS spectra were measured in the positive as well as in the negative mode. The highest peak observed in each spectrum in the positive mode is [M + Na] + , which is also in accordance with the calculated values.

The preparation of novel macromolecular prodrugs via the conjugation of two platinum(IV) complexes to suitably functionalized poly(organo)phosphazenes is presented. The inorganic/organic polymers provide carriers with controlled dimensions due to the use of living cationic polymerization and allow the preparation of conjugates with excellent aqueous solubility but long‐term hydrolytic degradability. The macromolecular Pt(IV) prodrugs are designed to undergo intracellular reduction and simultaneous release from the macromolecular carrier to present the active Pt(II) drug derivatives. In vitro investigations show a significantly enhanced intracellular uptake of Pt for the macromolecular prodrugs when compared to small molecule Pt complexes, which is also reflected in an increase in cytotoxicity. Interestingly, drug‐resistant sublines also show a significantly smaller resistance against the conjugates compared to clinically established platinum drugs, indicating that an alternative uptake route of the Pt(IV) conjugates might also be able to overcome acquired resistance against Pt(II) drugs. In vivo studies of a selected conjugate show improved tumor shrinkage compared to the respective Pt(IV) complex.

The 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 mecha-* Prof. Dr. M. Galanski Jurkat (T-lymphocytic leukemia, human) and SW480 (colon carcinoma, human) cells were kindly provided by the cell bank of the Institute