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Article Citation - WoS: 12Citation - Scopus: 13Novel Pt(ii) Complexes Containing Pyrrole Oxime, Synthesis, Characterization and Dna Binding Studies(Elsevier, 2014) Erdogan, Deniz Altunoz; Ozalp-Yaman, SenizSince the discovery of anticancer activity and subsequent clinical success of cisplatin (cis-[PtCl2(NH3)(2)]), platinum-based compounds have since been widely synthesized and studied as potential chemotherapeutic agents. In this sense, three novel nuclease active Pt(II) complexes with general formula; [Pt(NH3)CI(L)] (1), [Pt(L)(2)] (2), and K[PtCl2(L)] (3) in which L is 1-H-pyrrole-2-carbaldehyde oxime were synthesized. Characterization of complexes was performed by elemental analysis, FT-IR, H-1 NMR and mass spectroscopy measurements. Interaction of complexes (1-3) with calf thymus deoxyribonucleic acid (ct-DNA) was investigated by using electrochemical, spectroelectrochemical methods and cleavage studies. The hyperchromic change in the electronic absorption spectrum of the Pt(II) complexes indicates an electrostatic interaction between the complexes and ct-DNA. Binding constant values between 4.42 x 10(3) and 5.09 x 10(3) M-1 and binding side size values between 2 and 3 base pairs were determined from cyclic voltammetry (CV) and differential pulse voltammetry (DPV) studies. (C) 2014 Elsevier B.V. All rights reserved.Article Citation - WoS: 75Citation - Scopus: 80Unique Ligand-Based Oxidative Dna Cleavage by Zinc(ii) Complexes of Hpyramol and Hpyrimol(Wiley-v C H verlag Gmbh, 2007) Maheswari, Palanisamy Uma; Barends, Sharief; Oezalp-Yaman, Seniz; de Hoog, Paul; Casellas, Helene; Teat, Simon J.; Reedijk, JanThe zinc(II) complexes reported here have been synthesised from the ligand 4-methyl-2-N-(2-pyridylmethyl)aminophenol (Hpyramol) with chloride or acetate counterions. All the five complexes have been structurally characterised, and the crystal structures reveal that the ligand Hpyramol gradually undergoes an oxidative dehydrogenation to form the ligand 4-methyl-2-N-(2-pyridylmethylene)aminophenol (Hpyrimol), upon coordination to Zn-II. All the five complexes cleave the phi X174 phage DNA oxidatively and the complexes with fully dehydrogenated pyrimol ligands were found to be more efficient than the complexes with non-dehydrogenated Hpyramol ligands. The DNA cleavage is suggested to be ligand-based, whereas the pure ligands alone do not cleave DNA. The DNA cleavage is strongly suggested to be oxidative, possibly due to the involvement of a non-diffusible phenoxyl radical mechanism. ne enzymatic religation experiments and DNA cleavage in the presence of different radical scavengers further support the oxidative DNA cleavage by the zinc(II) complexes.Article Citation - WoS: 41Citation - Scopus: 48Platinated Copper(3-Clip Complexes as Effective Dna-Cleaving and Cytotoxic Agents(Wiley-v C H verlag Gmbh, 2008) Ozalp-Yaman, Seniz; de Hoog, Paul; Amadei, Giulio; Pitie, Marguerite; Gamez, Patrick; Dewelle, Janique; Reedijk, JanThe synthesis and biological activity of three heteronuclear platinum-copper complexes based on 3-Clip-Phen are reported. These rigid complexes have been designed to alter the intrinsic mechanism of action of both the platinum moiety and the Cu(3-Clip-Phen) unit. The platinum centers of two of these complexes are coordinated to a 3-Clip-Phen moiety, an ammine ligand and two chlorides, which are either cis or trans to each other. The third complex comprises two 3-Clip-Phen units and two chloride ligands bound in a trans fashion to the platinum ion. DNA-cleavage experiments show that the complexes are highly efficient nuclease agents. In addition, a markedly difference in their aptitude to perform direct double-strand cleavage is observed, which appears to be strongly related to the ability of the platinum unit to coordinate to DNA. Indeed, complex 6 is unable to coordinate to DNA, which is reflected by its incapability to carry out double-strand breaks. Nonetheless, this complex exhibits efficient DNA-cleavage activity, and its cytotoxicity is high for several cell lines. Complex 6 shows better antiproliferate activity than both cisplatin and Cu(3-Clip-Phen) toward most cancer cell lines. Furthermore, the cytotoxicity observed for 1 is for most cell lines close to that of cisplatin, or even better. Cu(3-Clip-Phen) induces very low cytotoxic effects, but a marked migratory activity. Complex 6 presents DNA-cleavage properties comparable to the one of Cu(3-Clip-Phen), but it does not show any migratory activity. Interestingly, both Cu(3-Clip-Phen) and 6 induces vacuolisation processes in the cell in contrast to complex 1 and cisplatin. Thus, the four complexes cisplatin tested, Cu(3-Clip-Phen), I and 6 stimulate different cellular responses.
