Experimental and Theoretical Studies on Biologically Active Lanthanide (III) Complexes (original) (raw)
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Chemical Physics, 2006
The binding mode of coumarin-3-carboxylic acid (HCCA) to La(III) is elucidated at experimental and theoretical level. The complexation ability of the deprotonated ligand (CCA À ) to La(III) is studied using elemental analysis, DTA and TGA data as well as FTIR, 1 H NMR and 13 C NMR spectra. The experimental data suggest the complex formula La(CCA) 2 (NO 3 )(H 2 O) 2 . B3LYP, BHLYP, B3P86, B3PW91, PW91P86 and MPW1PW91 functionals are tested for geometry and frequency calculations of the neutral ligand and all of them show bond length deviations bellow 1%. B3LYP/6-31G(d) level combined with large quasi-relativistic effective core potential for lanthanum is selected to describe the molecular, electronic and vibrational structures as well as the conformational behavior of HCCA, CCA À and La-CCA complex. The metal-ligand binding mode is predicted through molecular modeling and energy estimation of different La-CCA structures. The calculated atomic charges and the bonding orbital polarizations point to strong ionic metal-ligand bonding in La-CCA complex and insignificant donor acceptor interaction. Detailed vibrational analysis of HCCA, CCA À and La(C-CA) 2 (NO 3 )(H 2 O) 2 systems based on both calculated and experimental frequencies confirms the suggested metal-ligand binding mode.
Cytotoxic activity of new lanthanum (III) complexes of bis-coumarins
European Journal of Medicinal Chemistry, 2005
Complexes of lanthanum (III) with bis-coumarins: bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-2-yl-methane; bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-3-yl-methane and bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-4-yl-methane were synthesized by reaction of lanthanum (III) salt and the ligands, in amounts equal to metal/ligand molar ratio of 1:2. The complexes were prepared by adding an aqueous solution of lanthanum (III) salt to an aqueous solution of the ligand subsequently raising the pH of the mixture gradually to ca. 5.0 by adding dilute solution of sodium hydroxide. The lanthanum (III) complexes with bis-coumarins were characterized by different physicochemical methods-elemental analysis, IR-, 1 H-and 13 C-NMR spectroscopies and mass-spectral data. The spectral data of lanthanum (III) complexes were interpreted on the basis of comparison with the spectra of the free ligands. This analysis showed that in the La (III) complexes the ligands coordinated to the metal ion through both deprotonated hydroxyl groups. On the basis of the m(C=O) red shift observed, participation of the carbonyl groups in the coordination to the metal ion was also suggested. Cytotoxic screening by MTT assay was carried out. In the present study, we performed comparative evaluation of the cytotoxic effects of the three newly synthesized lanthanum complexes against the acute myeloid leukemia derived HL-60 and the chronic myeloid leukemia (CML)-derived BV-173. In addition the cytotoxic effects of La (III) complex with bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-2-yl-methane were evaluated on the SKW-3 cells. In order to elucidate some of the mechanistic aspects of the observed cytotoxic effects we evaluated the ability of this complex to trigger programmed cell death (apoptosis by means of agarose gel electrophoretic analysis of DNA), isolated from the cytosolic fraction of treated SKW-3 cells. In addition, microscopic morphological evaluation of the treated cells was carried out in order to establish morphological features indicative for programmed cell death.
Inorganic Chemistry, 2007
The interaction of lanthanide(III) cations (Ln(III) ) Sm(III), Eu(III), and Tb(III)) with the deprotonated form of the coumarin-3-carboxylic acid (cca -) has been investigated by density functional theory (DFT/B3LYP) and confirmed by reference MP2 and CCSD(T) computations. Solvent effects on the geometries and stabilities of the Ln(III) complexes were computed using a combination of water clusters and a continuum solvation model. The following two series of systems were considered: (i) Ln(cca) 2+ , Ln(cca) 2 + , Ln(cca) 3 and (ii) Ln(cca)(H 2 O) 2 Cl 2 , Ln(cca) 2 (H 2 O) 2 -Cl, Ln(cca) 3 . The strength and character of the Ln(III)−ccabidentate bonding were characterized by calculated Ln−O bond lengths, binding energies, ligand deformation energies, energy partitioning analysis, σ-donation contributions, and natural population analyses. The energy decomposition calculations predicted predominant electrostatic interaction terms to the Ln−cca bonding (ionic character) and showed variations of the orbital interaction term (covalent contributions) for the Ln−cca complexes studied. Electron distribution analysis suggested that the covalent contribution comes mainly from the interaction with the carboxylate moiety of cca -.
Acta pharmaceutica (Zagreb, Croatia), 2004
A complex of cerium(III) with 4-methyl-7-hydroxycoumarin was synthesized by mixing water solutions of cerium(III) nitrate and 4-methyl-7-hydroxycoumarin sodium salt in a metal-to-ligand molar ratio of 1:2. The complex was characterized and identified by elemental analysis, conductometry, IR, 1H and 13C NMR-spectroscopy, mass spectral data, DTA and TGA. Thermal analysis of the complex indicated the formation of a compound of the composition CeR2(OH).5H2O, R standing for the ligand. The reaction of cerium(III) with 4-methyl-7-hydroxycoumarin was studied in detail by the spectrophotometric method. The stepwise formation of two complexes, vis., CeR2+ and CeR2+, was established in the pH region studied. The equilibrium constants for 1:1 and 1:2 complexes were determined to be 10.72 and 9.22, respectively.
Spectroscopic evidence of La (III) complex of coumarin-3-carboxylic acid with cytotoxic activity
The complex of La(III) with coumarin-3-carboxylic acid (HCCA) has been synthesized and characterized with different physicochemical data, elemental analysis, DTA and TGA data, IR, Raman, 1 H NMR and 13 C NMR spectra. B3LYP method with 6-31G(d) and 6-31++G(d,p) basis sets was successfully applied to study the molecular, electronic and vibrational structures as well as the conformational behavior of the neutral and deprotonated ligand (CCA). FTIR and FT Raman spectra of the compounds were recorded in regions 4000 cm -1 to 400 cm -1 and 4000 cm -1 to 100 cm -1 respectively. Significant differences in the IR and Raman spectra of the complex were observed as compared to the spectra of the ligand. A detailed assignment of the observed fundamental bands of HCCA and La(III)-HCCA has been analyzed in terms of peak positions and relative intensities from the recorded FTIR and FTR spectra. The metal-ligand binding mode has been extensively studied on the basis of obtained spectral data. Detailed vibrational analysis of HCCA and La(III) complex gave evidence for bidentate coordination of CCA to La(III) -the metal ion binds through the oxygen atoms of the carbonylic and the deprotonated carboxylic groups of CCA in the complex formation. The new La(III) complex has revealed a strong cell proliferation inhibiting effect on K-562 cells and it may be used for treatment of resistant tumor cells.
New lanthanide complexes of 4-methyl-7-hydroxycoumarin and their pharmacological activity
Complexes of cerium(III), lanthanum(III) and neodymium(III) with 4-methyl-7-hydroxycoumarin (Mendiaxon, Hymecromone) were synthesized by the mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1 H and 13 C NMR spectroscopies and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity. The complexes of cerium(III) and neodymium(III) showed marginal cytotoxic activity against transformed leukemic cell lines (P3HR1 and THP-1) as compared to the inorganic salts. © 2001 É ditions scientifiques et médicales Elsevier SAS lanthanide complexes of Mendiaxon / anticoagulants / spasmolytic activity / cytotoxic activity * Correspondence and reprints: Tel.: +359-2-988 3142 ext. 269
Vibrational Spectroscopy, 2007
New complexes of cerium(III) and neodymium(III) with coumarin-3-carboxylic acid (HCCA) were synthesized and characterized. The elemental, DTA and TGA analyses showed the general formula, Ln(CCA) 2 (NO 3 )(H 2 O) (Ln = Ce, Nd). To suggest the binding mode of HCCA a detail vibrational investigation based on Raman, FTIR and DFT/B3LYP/SVP studies of HCCA, its deprotonated form (CCA À ), KCCA and Ln(CCA) 2 (NO 3 )(H 2 O) species, was performed. Two bidentate binding modes of CCA À to Ln(III) were modeled: (1) through the deprotonated carboxylic and the carbonylic oxygens and (2) through both the carboxylic oxygens. The vibrational analysis and the electronic energy calculations pointed to the first binding as more probable. The calculated vibrational spectra of the Ln(III) complexes with the second type binding (through both carboxylic oxygens) showed inconsistencies with the experimental spectra of the complexes. It was shown further that the direct comparison of the vibrational spectra of HCCA and Ln(III) complexes could be informative only to suggest the binding of CCA À to the Ln(III) ions but it does not give reliable information about the type of the binding mode. The model calculations indicated that the vibrational spectrum of KCCA is a better base for comparison with the Ln(III) complex spectra when it is used for prediction of the CCA À binding mode in the complexes studied. #
Acta pharmaceutica (Zagreb, Croatia), 2004
A complex of neodymium(III) with 4-hydroxy-3[1-(4-nitrophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one (acenocoumarol) was synthesized by mixing water solutions of neodymium(III) nitrate and the ligand (metal to ligand molar ratio of 1:3). The complex was characterized and identified by elemental analysis, conductivity, IR, 1H NMR and mass spectral data. DTA and TGA were applied to study the composition of the compound. Elemental and mass spectral analysis of the complex indicated the formation of a compound of the composition NdR3 x 6H2O, where R = C19H14NO6-) The reaction of neodymium(III) with acenocoumarol was studied in detail by the spectrophotometric method. The stepwise formation of three complexes, vis., NdR2+, NdR2+ and NdR3 was established in the pH region studied (pH 3.0-7.5). The equilibrium constants for 1:1, 1:2 and 1:3 complexes were determined to be log K1 = 6.20 +/- 0.06; log K2 = 3.46 +/- 0.07 and log K2) = 2.58 +/- 0.05, respectively.