Oksim Türevi Ligandlar İçeren Yeni Platin(II) Komplekslerinin Sentezi, Elektrokimyasal Karakterizasyonu ve DNA’ya Bağlanma Aktivitesi

The interest in platinum based antitumor drugs has been started in 1960’s with the serendipitous discovery by Rosenberg of the inhibition of cell division by platinum complexes. Cisplatin, cisdiamminedichloroplatinum(II), was approved by United Sates FDA in 1978 as an antitumor drug. It most effective against testicular and ovarian cancer. Despite the success of cisplatin chemotherapy, it has several serious side effects such as nausea, vomiting, nephrotoxicity, ototoxicity, neuropathy and myelosuppression. The other main reason for a failure of cisplatin chemotherapy is resistance of tumors to the drug. The resistance can be intrinsic or acquired and limits the applicability of cisplatin. Due to all of these reasons, the design and synthesis of more active, less toxic and orally active platinum drugs have been prompted in order to reduce severe side effects, to overcome drug resistance and to improve the patient’s quality of life. The main aim of this study is to synthesize novel platinum complexes with variety of ligands of oximes as potential anticancer drug leads providing better efficacy with low tissue resistance compared to cisplatin. Analysis of the products will be performed by UV-Vis, IR, ESR, ESCA, 1H-NMR, 13C-NMR ve 195Pt-NMR methods and the crystal structures will be identified by using X-ray diffraction spectrophotometer. The change in the DNA (Deoxyribonucleic acid: gene) conformation that is generated by the interaction (e.g groove binding, intercalation and H-bonding) of the complexes will be determined by electrophoresis with some spectroscopic and electrochemical methods.. Electrochemical behaviour of the complexes will be studied by cyclic voltammetry (CV) and the constant potental electrolyses of the complexes will be carried out at the peak potentials. The changes in the electronic absorption spectra of the complexes will be followed in situ by UV-vis spectrophotometer during the electrolysis in order to identify the electrolysis products and possible reaction intermediates. The number of the electrons that are transferred during the electrolysis will be counted by coulommetric methods and the presence of the unpaired electrons or the radicals will be proved by electron spin resonance spectroscopy. Moreover, the charges of the platinum ions present in the complex structure will be determined by ESCA and the structural identification of the complexes will also be performed by NMR (nuclear magnetic resonans) spectra besides X-ray diffraction spectrophotometer.