25 years after the first approval of cisplatin in the clinic against a number of cancer diseases, cisplatin and related compounds continue to be among the most efficient anticancer drugs used so far. Efforts are focused to develop novel platinum- and non-platinum-based antitumor drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. In the field of non-platinum compounds exhibiting anticancer properties, ruthenium complexes are very promising, showing activity on tumors which developed resistance to cisplatin or in which cisplatin is inactive. Furthermore, general toxicity was found to be very low. The first ruthenium compound NAMI-A entered phase I clinical trials in 1999 as an antimetastatic drug, whereas the ruthenium complex KP1019 will enter phase I clinical trials in 2003 as an anticancer drug which is among others very active against colon carcinomas and their metastases. Remarkable progress is also seen in developing tumor inhibiting gallium compounds. One of them, KP46, will also enter phase I clinical trials in 2003. This article reviews briefly the achievements in the field of anticancer metal complexes focusing the discussion onto the impact of the group of Bioinorganic Chemistry at the Department of Inorganic Chemistry at the University of Vienna. The development of pH sensitive platinum prodrugs, platinum-based drug targeting strategies with low-molecular-weight carriers, kinetically inert platinum(IV) complexes, as well as tumor inhibiting non-platinum anticancer drugs based on ruthenium and gallium is covered in the following sections.

A method of template synthesis yielded the following complexes of iron(IV) and 2,4-pentanedione bis(S-alkylisothiosemicarbazone) (H2R2L): [Fe(R2L)I], R = CH3 (1), C2Hs (2), /7-C3H7 (3), and «-C4H9 (4). The X-ray analysis of 2 showed the crystal belongs to the triclinic system, space group P\, with a = 8.622 (1) A, b = 8.764 (1) A, c = 13.058 (1) A, a = 73.38 (1)°, ß = 85.87 (1)°, = 68.96 (1)°, dak = 1.805 g cnr3, Z = 2, and molecular formula CnHi9FeIN6S2. The structure was solved by direct method using shelxs-86 and refined anisotropically by the least-squares method, employing 2137 unique reflections with / > 3 (1). The hydrogen atoms were located and refined by isotropic approximation. The final R was 0.022. Compound 2 has a square-pyramidal structure with the quadridentate ligand (R2L)3~i n the plane of the central ion (deviation from the pyramid base plane 0.389 A) and Iin the apical position. The results from magnetic measurements and Mdssbauer spectra for 1-4 indicate the S = 1 state for the central ion. The complexes were also characterized by mass spectrometry.

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The electron impact mass spectra of coordination compounds of nickel(I1) containing 14membered hexaaza macrocyclic ligands composed of S-substituted isothiosemicarbazide and Fdiketone units with cis and trans arrangement of SR groups were studied. The molecular ions exhibited the most intense peaks in all cases. The loss of peripheral groups is a common feature of the decomposition of the molecular ions for the compounds studied.Exchange between the hydrogen atoms of the alkylthio groups and the hydrogen at y-carbon atoms of the pdiketonate fragments was observed in the mass spectra of compounds with trans-SR groups. The molecular ions of the complexes with cis-SR groups selectively eliminated the radical R'.