ABSTRACT
We report here on three new ruthenium(II) complexes, [Ru(DPEPhos)(mtz)(bipy)]PF6 (Ru1), [Ru(DPEPhos)(mmi)(bipy)]PF6 (Ru2) and [Ru(DPEPhos)(dmp)(bipy)]PF6 (Ru3). DPEPhos = bis-[(2-diphenylphosphino)phenyl]ether, mtz = 2-mercapto-2-thiazoline, mmi = 2-mercapto-1-methylimidazole, dmp = 4,6-diamino-2-mercaptopyrimidine and bipy = 2,2'-bipyridine. The compounds were characterized by several spectroscopic techniques, and the molecular structure of Ru1 complex was determined by single-crystal X-ray diffraction. The cytotoxicity of Ru1 - Ru3 complexes were tested against the A549 (human lung) and the MDA-MB-231 (human breast) cancer cell lines and against MRC-5 (non-tumor lung) and MCF-10A (non-tumor breast) cell lines through the MTT assay. All three complexes are cytotoxic against the cell lines studied, with IC50 values lower than those found for the cisplatin. Among them, the Ru2 complex has shown the best selectivity against MDA-MB-231 cancer cell lines, with an IC50 value 12 times lower than that on MCF-10A. The complex Ru2 was capable to induce changes in MDA-MB-231 cells morphology, with loss of cellular adhesion, inhibited colony formation and induce an accumulation of cells at the sub-G1 phase, with an increase in S-phase and decrease of cells at G2 phase. Viscosity, electrochemical and Hoechst 33258 displacement experiments for Ru1 - Ru3 complexes with calf thymus DNA (CT-DNA) showed an electrostatic and groove binding mode of interaction. Additionally, the complexes interact with the protein Human Serum Albumin (HSA) by static mechanism. The negative values for ΔH and ΔS indicate that van der Waals forces and hydrogen bonding may occurs between the complexes and HSA. Therefore, this class of complexes are promising anticancer candidates and may be selected to further detailed studies.
Subject(s)
Antineoplastic Agents , Coordination Complexes , Ruthenium , Humans , Cell Line, Tumor , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Molecular Structure , Ethers , Ruthenium/chemistryABSTRACT
This study describes the synthesis of a new ruthenium nitrosyl complex with the formula [RuCl(2)NO(BPA)] [BPA = (2-hydroxybenzyl)(2-methylpyridyl)amine ion], which was synthesized and characterized by spectroscopy, cyclic voltammetry, X-ray crystallography, and theoretical calculation data. The biological studies of this complex included in vitro cytotoxic assays, which revealed its activity against two different tumor cell lines (HeLa and Tm5), with efficacy comparable to that of cisplatin, a metal-based drug that is administered in clinical treatment. The in vivo studies showed that [RuCl(2)NO(BPA)]is effective in reducing tumor mass. Also, our results suggest that the mechanism of action of [RuCl(2)NO(BPA)] includes binding to DNA, causing fragmentation of this biological molecule, which leads to apoptosis.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Ruthenium Compounds/chemistry , Ruthenium Compounds/pharmacology , Animals , CHO Cells , Cell Line, Tumor , Cricetinae , Cricetulus , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Humans , Mice , Mice, Inbred C57BL , Models, Molecular , Spectrum Analysis/methodsABSTRACT
Three new iron(III) complexes with the ligand N,N'-bis(2-hydroxybenzyl)-N,N'-bis(pyridin-2-ylmethyl)ethylenediamine, H2bbpen, containing electron-donating and -withdrawing groups (Me, Br, NO2) in the 5-position of the phenol rings were synthesized and fully characterized by IR spectroscopy, ESI mass spectrometry, and CHN elemental analyses. X-ray structures of the iron(III) complexes containing NO2 and Me groups were determined. The effects of the substituents on the electronic properties of the complexes were detected by UV-visible spectroscopy, cyclic voltammetry, and X-ray crystallography. Linear correlations between the Hammett parameter for the substituents (sigma(p)) and the Fe(III)/Fe(II) redox potentials or ligand-metal charge-transfer (LMCT) processes of the complexes were obtained. A theoretical study using DFT is presented and shows good agreement between the experimental and calculated data.
Subject(s)
Electrons , Enzymes/chemistry , Ethylenediamines/chemistry , Ferric Compounds/chemistry , Metalloproteins/chemistry , Pyridines/chemistry , Tyrosine/chemistry , Crystallography, X-Ray , Electrochemistry , Ferric Compounds/chemical synthesis , Ligands , Models, Molecular , Molecular Structure , Sensitivity and Specificity , Spectrophotometry, Ultraviolet/methodsABSTRACT
The potential energy surface (PES) for the HOBr.H(2)O complex has been investigated using second- and fourth-order Møller-Plesset perturbation theory (MP2, MP4) and coupled cluster theory with single and doubles excitations (CCSD), and a perturbative approximation of triple excitations (CCSD-T), correlated ab initio levels of theory employing basis sets of triple zeta quality with polarization and diffuse functions up to the 6-311++G(3dp,3df ) standard Pople's basis set. Six stationary points being three minima, two first-order transition state (TS) structures and one second-order TS were located on the PES. The global minimum syn and the anti equilibrium structure are virtually degenerated [DeltaE(ele-nuc) approximately 0.3 kcal mol(-1), CCSD-T/6-311++G(3df,3pd) value], with the third minima being approximately 4 kcal mol(-1) away. IRC analysis was performed to confirm the correct connectivity of the two first-order TS structures. The CCSD-T/6-311++G(3df,3pd)//MP2/6-311G(d,p) barrier for the syn<-->anti interconversion is 0.3 kcal mol(-1), indicating that a mixture of the syn and anti forms of the HOBr.H(2)O complex is likely to exist.
