Some host-guest activity of dichloro(ethylenediamine)palladium(II) complexes with different ligands, such as guanosine 5'-monophosphate (5'-GMP), 4,4'-bipyridine (4,4'-bipy) and 2,4,6-tri(4-pyridyl)-1,3,5-triazine (Py 3T) as the host and various small organic molecules as a guest was investigated. The known antitumor drugs altretamine, flutamide and cyclophosphamide were putative guest molecules. No host-guest interaction was observed for [Pd(en)(4,4'-bipy)] 48+ (en = ethylenediamine) with the molecules under study. For [Pd(en)(5'-GMP)]4, a weak interaction was observed with altretamine, but not with flutamide or cyclophosphamide. All three guest molecules were shown to form host-guest complexes with the host complex [(Pd(en))6(Py 3T)4]12+. The stoichiometry was determined for all three host-guest complexes, and for the host-guest complex of [(Pd(en)) 6(Py3T)4]12+ with flutamide, the role of the solvent was investigated. The purpose of these studies was to characterize these host-guest complexes in order to possibly test their potential anti-tumor activity against several tumor cell lines. High-field NMR spectroscopy was used as the main tool for the characterization of the host-guest interaction as well as for the determination of the host-guest stoichiometry.
The second part of my research dealt with synthesis and characterization of some palladium(II) complexes of proflavine (Pro). Palladium complexes that were employed were dichloro(ethylenediamine)palladium(II) and its nitrato analog, potassium tetrachloropalladate(II), (2,2':6',2"-terpyridine)palladium(II) nitrate and (2,2'-bipyridine)palladium(II) nitrate. Proflavine is used in the pharmacological field for various purposes and is known to interact by intercalation with cellular DNA. Since one of the purposes of the research was to investigate whether some palladium complexes can serve as antitumor drugs, this ligand was chosen to serve as a candidate to bind with palladium complexes. By using proflavine with palladium complexes, a therapeutic synergistic effect might be expected due to the intercalation of the proflavine into DNA combined with the covalent binding of palladium(II) with DNA. It was shown that [Pd(terpy)(H2O)2](NO3)2 binds to proflavine through the central nitrogen. However, [Pd(en)(H2O) 2](NO3)2 binds through the nitrogen of an amino group, and the complex in which only one Pd(en)2+ is coordinated to the amino group of proflavine was isolated. [PdCl4]2- binds through the amino groups, forming a polymeric structure. When this complex is dissolved in DMSO the product forms two species. One of them is a 2:1 complex in which Pd(II) is bound to each of the amino groups and the other is a 1:2 complex in which one Pd(II) is bound through the endocyclic nitrogen to two proflavine molecules. The complexes Pd(terpy)Pro, (formed from Pd(terpy)2+ and Pro), Pd(en)Pro (formed from Pd(en) 2+ and Pro) and PdClPro (formed from K2PdCl4 and Pro) were characterized by various techniques, including high-field NMR spectroscopy, electro-spray ionization mass spectroscopy (ESI-MS), IR and UV spectroscopies.
Cytotoxicity studies of [Pd(en)(5'-GMP)]4 and [Pd(en)(H 2O)2](NO3)2 as well as the synthesized Pd(terpy)Pro and PdClPro complexes were performed against several cancer cell lines: breast (SK-BR-3, MCF-Her-2-6, MDA-MB), ovarian (SK-OV-3,) and normal cells (BJ). The most promising results were obtained for Pd(terpy)Pro and PdClPro, for which the survival rate against breast cancer line (SK-BR-3) at the concentration of 10 μM was 16.2% and 26.1%. The survival rate against normal cells was 78.2% and 84%, respectively.
