ABSTRACT
Two ternary Zn(II) complexes, with 1,10-phenanthroline (phen) as the main ligand and a carboxylate-containing ligand [dipicolinate (dipico) or L-threoninate (L-Thr)] as the subsidiary ligand, were prepared and characterized by elemental analysis, Fourier transform IR, UV, and fluorescence spectroscopy, X-ray diffraction, molar conductivity, and electrospray ionization mass spectrometry. X-ray structure analysis shows that both [Zn(phen)(dipico)(H(2)O)]·H(2)O (1) and [Zn(phen)(L-Thr)(H(2)O)Cl]·2H(2)O (2) have octahedral geometry about the Zn(II) atom. Both complexes can inhibit topoisomerase I, and have better anticancer activity than cisplatin against nasopharyngeal cancer cell lines, HK1 and HONE-1, with concentrations causing 50 % inhibition of cell proliferation (IC(50)) in the low micromolar range. Complex 2 has the highest therapeutic index for HK1. Both Zn(II) complexes can induce cell death by apoptosis. Changing the subsidiary ligand in the Zn(II) complexes affects the UV-fluorescence spectral properties of the coordinated phen ligand, the binding affinity for some DNA sequences, nucleobase sequence-selective binding, the phase at which cell cycle progression was arrested for treated cancer cells, and their therapeutic index.
Subject(s)
Antineoplastic Agents/chemical synthesis , Coordination Complexes/chemical synthesis , Phenanthrolines/chemistry , Pyridines/chemistry , Threonine/chemistry , Zinc/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cisplatin/chemistry , Cisplatin/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Crystallography, X-Ray , Humans , Inhibitory Concentration 50 , Models, Molecular , Molecular Structure , Phenanthrolines/pharmacology , Spectroscopy, Fourier Transform Infrared , Topoisomerase Inhibitors/chemistry , Topoisomerase Inhibitors/pharmacologyABSTRACT
The synthesis and characterization of two cobalt(II) complexes, Co(phen)(ma)Cl 1 and Co(ma)(2)(phen) 2, (phen=1,10-phenanthroline, ma(-)=maltolate or 2-methyl-4-oxo-4H-pyran-3-olate) are reported herein. The complexes have been characterized by FTIR, CHN analysis, fluorescence spectroscopy, UV-visible spectroscopy, conductivity measurement and X-ray crystallography. The number of chelated maltolate ligands seems to influence their DNA recognition, topoisomerase I inhibition and antiproliferative properties.
Subject(s)
Cobalt/chemistry , Organometallic Compounds/chemical synthesis , Organometallic Compounds/pharmacology , Phenanthrolines/chemistry , Pyrones/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Survival/drug effects , Chelating Agents/chemical synthesis , Chelating Agents/chemistry , Chelating Agents/pharmacology , Crystallography, X-Ray , DNA/chemistry , DNA/metabolism , DNA Topoisomerases, Type I/metabolism , Female , Humans , Inhibitory Concentration 50 , Ligands , Organometallic Compounds/chemistry , Spectrum AnalysisABSTRACT
The nitrilo-triacetate trianion in the title compound, [Zn(2)(C(6)H(6)NO(6))(C(12)H(8)N(2))(3)]NO(3)·6H(2)O, is engaged in N,O,O',O"-chelation to the phenanthroline-chelated Zn(II) unit, giving a distorted octa-hedral geometry for the metal atom. One of the three O atoms of the trianion that is engaged in chelation also binds to the bis-(phenanthroline)-chelated Zn(II) unit, whose five-coordinate geometry is distorted owing to a long Znâ¯O inter-action [2.401â (2)â Å]. The dinuclear cations, nitrate anions and uncoordinated water mol-ecules are linked into a three-dimensional network via O-Hâ¯O hydrogen bonds between water molecules and carboxylate O atoms.
