The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)‐based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum‐based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)‐based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine‐N,N′‐di‐3‐propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress‐independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical‐mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy. © 2005 Wiley‐Liss, Inc.

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The reaction of [Pt(en)(H(2)O)(2)](2+) with 1 equivalent of 1-methylcytosine at an initial pH of 6 ultimately led to the 1-methylcytosinato-bridged (ethylenediamine)platinum(II) dimer, [(en)Pt(MetCyt-H)(2)Pt(en)](NO(3))(2) (1). The species during the reactions prior to formation of 1 have been investigated by using (195)Pt NMR spectroscopy. From the reaction mixture the [Pt(en)(MetCyt)(2)](NO(3))(2) complex (3) could be isolated and structurally characterized. A rational synthesis of 1 was also achieved by dimerization of [Pt(en)(MetCyt)(H(2)O)](NO(3))(2). According to X-ray structure analysis, the Pt-Pt distance of 2.9816(3) A in 1 is well comparable with the corresponding value found in the cis-diammineplatinum(II) analog (2.981(2) A). Oxidation of 1 with K(2)S(2)O(8) led to the symmetrically sulfate-capped diplatinum(III) complex with two ethylenediamine ligands equatorially bound to the two Pt atoms ht-[(SO(4))(en)Pt(MeCyt-H)(2)Pt(en)(SO(4))] (5), as established by X-ray crystallography. When the oxidation was carried out in the presence of HClO(4), the formation of the hydroxido/aqua ht-1-methylcytosinato bridged (en)Pt(III) dimer ht-[H(2)O(en)Pt(MetCyt-H)(2)Pt(en)OH](ClO(4))(3) (6) was observed, as supported by elemental and X-ray structure analysis. In the structure of 6, two ethylenediamine ligands are differently bound to the two Pt centers: one of them equatorially while the second one caps the opposite axial site of the diplatinum(III) core. The Pt-Pt distances in the platinum(iii) dimers are 2.5982(4) in 5 and 2.5569(3) A in 6.

Pure and Pt-doped ZnO nanophase particles were synthesized by ultrasonic spray pyrolysis. The particles were obtained through the decomposition of zinc nitrate and with a newly developed Pt(IV) complex with 1,3-propylenediamine-N,N′-diacetate tetradentate class ligand (pdda). The complex was characterized by elemental analysis, electronic absorption and infrared spectroscopy. The form of the determined complex structure {trans-[Pt(pdda)Br2]·H2O} implies that Pt(IV) ion has a distorted octahedral coordination due to intramolecular N–H···Br interaction. The results of structural refinement (cell parameters, bond lengths, and ion occupancy) of ultrasonically derived pure and Pt-doped ZnO particles suggest either the formation of Zni interstitials or platinum ion incorporation into the ZnO lattice in octahedral interstitial positions, respectively. A well-crystallized hexagonal wurtzite structure of ZnO was pronounced in all investigated samples [JCPDS card 36-1415, Joint Committee on Powder Diffraction Standards, defined by International Centre for Diffraction Data (www.icdd.com)]. Phase determination also indicated the presence of a nitrate hydroxide hydrate phase (JCPDS card 24-1460), as a result of incomplete precursor decomposition and a spinel Zn2PtO4 phase (below 1.0 wt%) located in the boundary region for a Pt-doped ZnO sample. Based on x-ray diffraction, scanning electron microscopy, and energy-dispersive spectroscopy analyses, it was shown that the different particle growingmorphologies, which were either spheroidally or pyramidally shaped, were influenced by the precursor chemistry, processing parameters and the presence of platinum ions. The composite internal particle structure revealed by transmission electron microscopy and selected area electron diffraction analyses, implied that the secondary particles represent an assembly of primary particles sized under 60 nm aroused during the processes of nucleation, growth and aggregation. Both hexagonal and spheroidal shape of primary particles was evident. The particle morphology, primarily particle size and the mechanism of Pt4+ ion introduction into the ZnO cell was discussed based on the structural refinement and selected area electron diffraction analysis.