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1.
To perform biological evaluations of newly-designed Pt(II) and Pd(II) complexes, the present study was conducted with targeted protein human serum albumin (HSA) and HCT116 cell line as model of human colorectal carcinoma. The binding of Pt(II) and Pd(II) complexes to HSA was analyzed using fluorescence spectroscopy and molecular docking. The thermal stability and alterations in the secondary structure of HSA in the presence of Pt(II) and Pd(II) complexes were investigated using the thermal denaturation method and circular dichroism (CD) spectroscopy. The cytotoxicity of the Pt(II) and Pd(II) complexes was studied against the HCT116 cell line using MTT assay. The binding analysis revealed that the fluorescence findings were well in agreement with docking results such that there is only one binding site for each complex on HSA. Binding constants of 8.7?×?103 M?1, 2.65?×?103 M?1, 0.3?×?103 M?1, and 4.4?×?103 M?1 were determined for Pd(II) and Pt(II) complexes (I–IV) at temperature of 25?°C, respectively. Also, binding constants of 1.9?×?103 M?1, 15.17?×?103 M?1, 1.9?×?103 M?1, and 13.1?×?103 M?1 were determined for Pd(II) and Pt(II) complexes (I–IV) at temperature of 37?°C, respectively. The results of CD and thermal denaturation showed that the molecular structure of HSA affected by interaction with Pt(II) and Pd(II) complexes is stable. Cytotoxicity studies represented the growth suppression effect of the Pt(II) and Pd(II) complexes toward the human colorectal carcinoma cell line. Therefore, the results suggest that the new designed Pt(II) and Pd(II) complexes are well promising candidates for use in cancer treatment, particularly for human colorectal cancer.

Communicated by Ramaswamy H. Sarma  相似文献   


2.
Imidazole analogs are the agents that attract both bioinorganic chemist and drug designer. Numerous methods have been proposed for synthesis of imidazole derivatives. In this study, a series of heterocyclic system with p-conjugated system such as 2-aryl-imidazo[4,5-f][1,10]phenanthroline analogs were synthesized. Then, three new palladium(II) complexes containing 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1,10]Phenanthroline (FIP) and 2-(thiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (TIP) ligands were synthesized. The structures of the compounds, [Pd(Phen)(TIP)](NO3)2, [Pd(Phen)(FIP)](NO3)2, and [Pd(FIP)2]Cl were determined by spectroscopic methods and elemental analysis. Biological activity of the complexes synthesized was assessed against chronic myelogenous leukemia cell line, K562. Also, the interactions of human serum albumin with complexes were investigated using isothermal titration in the Tris buffer, pH 7.4. According to the results obtained, it was found that there is a set of six binding sites for these complexes on HSA with positive cooperativity in the binding process. Docking technique was also applied to confirm the experimental results. The results showed that smaller complexes have higher interaction affinity.  相似文献   

3.
A series of (1-(benzyl (aryl) amino) cyclohexyl) methyl esters 7a-n were prepared and screened for their anticonvulsant profile. Screening of these esters 7a-n and their starting alcohols 6a and 6b revealed that compound 7k was the most potent one in the scPTZ screening test with an ED50 value of 0.0056 mmol/kg being about 10- and 164-fold more potent than phenobarbital (ED50 = 0.056 mmol/kg) and ethosuximide (ED50 = 0.92 mmol/kg) as reference drugs, respectively. Meanwhile, in the MES test, compounds 7b and 7k at doses 0.0821 mmol/kg and 0.0334 mmol/kg, exerted 66% and 50% protection of the tested mice, respectively, compared with diphenylhydantoin, which exerted 100% protection at dose 0.16 mmol/kg. In the neurotoxicity screen test, almost all esters 7a-n did not show any minimal motor impairment at the maximum administrated dose. The anticonvulsant effectiveness of esters 7a-n was higher than their corresponding alcohols 6a and 6b. Compounds 7b and 7k exhibited pronounced anticonvulsant activity devoid of neurotoxicity in minimal motor impairment test and hepatotoxicity in the serum enzyme activity assay. 3D pharmacophore model using Discovery Studio 2.5 programs showed high fit value. The obtained experimental results of sc-PTZ activity of compounds 7a-n was consistent with the molecular modeling study.  相似文献   

4.
The Pd(II) complexes of a 2N-donor ligand containing a pendent indole, 3-(2-pyridylmethylamino)ethylindole (L), were synthesized and characterized. Reaction of the ligand with [PdCl2(CH3CN)2] at room temperature gave [Pd(L)Cl2] (1) as pale yellow crystals. The X-ray crystal structure analysis and 1H NMR spectrum of 1 revealed that the complex has a 2N2Cl-donor set in a square-planar geometry and that the pendent indole ring has no characteristic intramolecular interaction with the Pd(II) ion and the coordinated pyridine moiety. Refluxing a solution of 1 in CH2Cl2/DMF for a few hours under basic conditions gave yellow crystals, which were shown to be an indole-C2 binding complex [Pd(L)Cl] (2) by X-ray analysis. Conversion of complex 1 to 2 in DMSO was observed upon dilution of the solution of complex 1. From solution equilibrium and kinetic studies the initial step of the conversion by dilution has been assigned to the replacement of a coordinated Cl ion with the DMSO molecule. The ligand replacement easily occurred at low concentrations of 1. The complex with a coordinated solvent molecule exhibited a high reactivity and formed a stable Pd-C bond with the indole ring located close to the Pd(II) center. We discussed the concentration dependent formation of the indole-C2 binding complex 2 and its detailed mechanism.  相似文献   

5.
BackgroundSchiff base metal complexes are considered promising chemotherapeutic agents due to their potential application in cancer therapy.MethodsThe current work sought to synthesize a brand-new Schiff base ligand obtained from 2-hydroxybenzohydrazide and (E)− 1-(2-(p-tolyl)hydrazono)propan-2-one with metal ions which included Pd(II) and Zn(II) ions. Elemental analyses, FT-IR, mass spectra, 1H NMR, UV-Vis spectrometer, and computational analysis characterized the compound's structure. In vitro, the breast cancer cell line (MCF-7) was tested for its sensitivity to Schiff base (HL) and its Pd(II) and Zn(II) complexes. The half-maximal inhibitory concentration IC50 of the compounds was determined and used to perform the comet assay, which was carried out to reveal the photo-induced DNA damaging ability of the compounds of individual cells. Moreover, the compounds' effects on antioxidant defense systems of enzymes in cells: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and oxidant Malondialdehyde (MDA) were examined in MCF-7 cells.ResultsThe Pd(II) complex displayed approximately the same IC50 as Cisplatin, while Zn(II) complex had better activity than Cisplatin with very low IC50, 1.40 μg/ml. Significant alterations in SOD, CAT, GPx, and MDA production were discovered, inducing oxidative stress, enlarging ROS production, and reducing the antioxidant amount. This change was approximately similar in most compounds. Consequently, it promoted apoptosis, particularly the Zn(II) complex, which demonstrated an improved impact because of its ability to influence the antioxidant defense systems of enzymes, mostly SOD and GPx, besides increasing MDA levels.ConclusionIt can be concluded that Zn(II) complex is the most effective anticancer drug since it induced a very similar genotoxic effect as Cisplatin and has a very low IC50 value.  相似文献   

6.
The reaction of Zn(κ2O,O′-OAc)2·2H2O with two equiv of 3,5-lutidine in methanol at room temperature for 12 h afforded [Zn(OAc)2(3,5-lutidine)2]· H2O (1) in 91% yield. The acetate exchange reaction of 1 with two equiv of aryl carboxylic acids in methanol at room temperature for 12 h afforded [Zn(μ2-κ1O:κ1O′-O2CAr)2(3,5-lutidine)]2 [Ar = C6H5 (2) and C6H4Me-3 (3)], [Zn(OC(O)C6H4Me-2)2(3,5-lutidine)2] (4) and [Zn(κ2O,O′−O2CC6H4Me-4)2(3,5-lutidine)2] (5) in ?90% yield. Complexes 1-5 were characterized by microanalytical, IR, solution (1H and 13C) and solid-state cross-polarization magic angle spinning 13C NMR and X-ray diffraction data. The zinc atom in 1 is surrounded by nitrogen atom of two 3,5-lutidine and oxygen atom of two monodentate acetate moiety and thus attains a tetrahedral geometry. One of the acetate moieties is hydrogen bonded with a water molecule in the crystal lattice. Complexes 2 and 3 possess a dinuclear paddlewheel framework with a square pyramidal geometry around the zinc atom whereas 4 and 5 are mononuclear species with the zinc atom in tetrahedral and an octahedral geometry, respectively. Thermogravimetric analyses of 2-5 suggested ZnO as the decomposed product followed by the confirmation from the powder X-ray diffraction patterns. Enormous gas evolution resulting in porous ZnO during thermal decomposition was evidenced from scanning electron microscopic images.  相似文献   

7.
A new series of square planar palladium(II) complexes with pincer ligands, pip2NCN (pip2NCNH = 1,3-bis(piperidylmethyl)benzene) and pip2NNN (2,6-bis(piperidylmethyl)pyridine), has been prepared: Pd(pip2NCN)X (X = Cl, Br, I), [Pd(pip2NCN)(L)](BF4) (L = pyridine, 4-phenylpyridine), and [Pd(pip2NNN)Cl]Cl. The X-ray crystal structures of Pd(pip2NCN)Br, [Pd(pip2NCN)(L)]BF4, and [Pd(pip2NNN)Cl]Cl confirm the tridentate coordination geometries of the pincer ligands. For the pip2NCN complexes, each piperidyl ring adopts a chair conformation with the metal center at an equatorial position on the N(piperidyl) atom. However, one of the piperidyl groups of Pd(pip2NNN)Cl+ adopts a previously unobserved coordination geometry, effectively placing the metal center at an axial position on the N(piperidyl) atom. 1H NMR and UV-Vis absorption measurements provide additional insight into the electronic structures of these complexes. The 1H NMR spectra of Pd(pip2NCN)X (X = Cl, Br, I) are consistent with deshielding of the pip2NCN ligand resonances along the Cl < Br < I series, in opposition to the relative halogen electronegativities. It is suggested that this trend is consistent with decreasing filled/filled repulsions between the dπ orbitals of the metal center and the lone pair orbitals of the halide ligands along this series. Electronic absorption spectra support the notion that ligand-to-metal charge-transfer states are stabilized in these palladium(II) complexes relative to their platinum(II) analogues.  相似文献   

8.
Reaction of Ni(OAc)2 with the symmetric `end-off' compartmental proligand 2,6-[N,N-bis(2-hydroxy-phenylmethyl)-N,N-bis(2-pyridylmethyl)aminomethyl]-4-methylphenol (H3L) in the presence of NaPF6 has been found to generate a homotetranuclear nickel(II) complex [(Ni4HL)(L)(OAc)2(H2O)2(HOAc)2]PF6. The crystal structure of the complex reveals that the complex is donor asymmetric and that the extended supra-ligand periphery is maintained by a tight hydrogen-bond between two pendant phenol/phenoxy groups of adjacent ligands and by further tight hydrogen-bonds between coordinated acetic acid molecules and the remaining pendant phenols of the ligand, generating a double acid salt of the type [CH3COO?H?LH?L?H?OOCCH3]5−. Reaction of H3L with Ni(OAc)2 and NaClO4 in methanol gave the complex [Ni2(HL)(OAc)2(OH2)2][ClO4]. The structure was determined by X-ray diffraction and showed that the complex exists as a dimer promoted by intermolecular hydrogen-bonding.  相似文献   

9.
Palladium(II) complexes are potential antitumor metallodrugs for their chemical resemblance to platinum(II) complexes. Two palladium(II) complexes (1 and 2) in the formula of [PdLnCl] [L1 = N-(tert-butoxycarbonyl)-l-methionine-N′-8-quinolylamide, L2 = L-alanine-N′-8-quinolylamide] have been synthesized accordingly. The structures of the complexes were fully characterized by X-ray crystallography. The palladium(II) center in 1 is coordinated by two N atoms and an S atom from L1 with one chloride anion as the leaving group; while that in 2 is coordinated by three N atoms from L2 with one chloride anion as the leaving group. The interaction between complex 1 and human serum albumin (HSA) has been investigated using fluorescence and circular dichroism spectroscopies. The complex seems to react with HSA chiefly through hydrophobic and electrostatic interactions, and it does not alter the α-helical nature of HSA. The cytotoxicity of these complexes has been tested against the human cervical cancer (HeLa), human mammary cancer (MCF-7), and human lung cancer (A-549) cell lines. Complex 1 displays a cytotoxic activity comparable to that of cisplatin, but complex 2 is less active than cisplatin.  相似文献   

10.
Four complexes [Pd(L)(bipy)Cl]·4H2O (1), [Pd(L)(phen)Cl]·4H2O (2), [Pt(L)(bipy)Cl]·4H2O (3), and [Pt(L)(phen)Cl]·4H2O (4), where L = quinolinic acid, bipy = 2,2’-bipyridyl, and phen = 1,10-phenanthroline, have been synthesized and characterized using IR, 1H NMR, elemental analysis, and single-crystal X-ray diffractometry. The binding of the complexes to FS-DNA was investigated by electronic absorption titration and fluorescence spectroscopy. The results indicate that the complexes bind to FS-DNA in an intercalative mode and the intrinsic binding constants K of the title complexes with FS-DNA are about 3.5?×?104 M?1, 3.9?×?104 M?1, 6.1?×?104 M?1, and 1.4?×?105 M?1, respectively. Also, the four complexes bind to DNA with different binding affinities, in descending order: complex 4, complex 3, complex 2, complex 1. Gel electrophoresis assay demonstrated the ability of the Pt(II) complexes to cleave pBR322 plasmid DNA.  相似文献   

11.
The distorted square-planar complexes [Pd(PNHP)Cl]Cl (1) (PNHP = bis[2-(diphenylphosphino)ethyl]amine), [M(P3)Cl]Cl [P3 = bis[2-(diphenylphosphino)ethyl]phenylphosphine; M = Pd (2), Pt (3)] and [Pt(NP3)Cl]Cl (5) (NP3 = tris[2-(diphenylphosphino)ethyl]amine), coexisting in the later case with a square-pyramidal arrangement, react with one equivalent of CuCl to give the mononuclear heteroionic systems [M(L)Cl](CuCl2) [L = PNHP, M = Pd (1a); L = P3, M = Pd (2a), Pt (3a); L = NP3, M = Pt (5a)]. The crystal structure of 3a confirms that Pt(II) retains the distorted square-planar geometry of 3 in the cation with P3 acting as tridentate chelating ligand, the central P atom being trans to one chloride. The counter anion is a nearly linear dichlorocuprate(I) ion. However, the five-coordinate complexes [Pd(NP3)Cl]Cl (4), [M(PP3)Cl]Cl (M = Pd (6), Pt (7); PP3 = tris[2-(diphenylphosphino)ethyl] phosphine) containing three fused five-membered chelate rings undergo a ring-opening by interaction with one (4, 6, 7) and two (6, 7) equivalents of CuCl with formation of neutral MCu(L)Cl3 [L = NP3, M = Pd (4a); L = PP3, M = Pd (6a), Pt (7a)] and ionic [MCu(PP3)Cl2](CuCl2) [M = Pd (6b), Pt (7b)] compounds, respectively. The heteronuclear systems were shown by 31P NMR to have structures where the phosphines are acting as tridentate chelating ligands to M(II) and monodentate bridging to Cu(I). Further additions of CuCl to the neutral species 6a and 7a in a 1:1 ratio resulted in the achievement of the ionic complexes 6b and 7b with ions as counter anions. It was demonstrated that the formation of heterobimetallic or just mononuclear mixed salt complexes was clearly influenced by the polyphosphine arrangement with the tripodal ligands giving the former compounds. However, complexes [M(NP3)Cl]Cl constitute one exception and the type of reaction undergone versus CuCl is a function of the d8 metal centre.  相似文献   

12.
A new class of mononuclear metal complexes with 1-methylimidazole-2-aldoximate (miao) has been synthesized and characterized: trans-NiII(Cl)2(Hmiao)2 (1), trans-NiII(miao)2(py)2 (2), NO-trans-NiII(miao)2(phen) (3), and NO-trans-FeII(miao)2(phen) (4). The crystal structures of 2, 3, and 4 have been determined by single-crystal X-ray crystallography. Compound 1 having the protonated miao ligand (i.e., Hmiao) is a precursor for synthesizing 2 and 3. Compound 2 is an octahedral NiII complex surrounded by two miao bidentate ligands and two monodentate ligands of pyridine in a trans-arrangement. Compound 3 is a cis-type octahedral NiII complex with two miao ligands and a bidentate ligand of 1,10-phenanthroline, in which the ligand arrangement around NiII center is found in an NO-trans form. Compound 4 is an isostructural FeII derivative of 3. Compounds 1, 2, and 3 exhibit paramagnetic nature with an S = 1 spin and a positive zero-field splitting, among which it for 3 is overlapped with intermolecular ferromagnetic interaction (zJ/kB = +0.16 K). Compound 4 is diamagnetic due to the existence of low-spin FeII ion.  相似文献   

13.
Synthesis, structure and spectroscopic characterization of 2-thiophenealdehyde-N(4)-napthylthiosemicarbazone and its complexes with biologically important Zn(II) and toxic Hg(II) metal ions have been reported. The crystal structure of the complexes reveals that both are distorted tetrahedral. In the Hg(II) complex the ligand is neutral and mondented where as in Zn(II) complex the ligand is bidented and anionic. Whereas conductivity measurement study shows both the complexes are molecular species. The beautiful changes in absorption spectra along with isosbestic points upon addition of respective metal salts to the ligand solution convincingly support the formation of metal complexes in solution phase. The other spectroscopic studies also show good correlation with their solid state structures.  相似文献   

14.
Eight mononuclear Pd(II) complexes containing salicylaldiminato thiosemicarbazones (saltsc-R; where R = H (1), 3-OMe (2), 3-tBu (3) and 5-Cl (4)) as dinegative tridentate ligands were prepared by the reaction of the corresponding thiosemicarbazone with the precursor Pd(L)2Cl2 (L = phosphatriazaadamantane or 4-picoline) in the presence of a weak base. These complexes (9-16) were characterised by a range of spectroscopic and analytical techniques including NMR spectroscopy and X-ray diffraction. These complexes along with four other Pd(II) analogues (5-8) were screened for activity in vitro against the Trichomonas vaginalis parasite. Preliminary results show that the type of ancillary ligand as well as the substituents on the aromatic ring of the salicylaldiminato thiosemicarbazone ligand influences the antiparasitic activity of these complexes.  相似文献   

15.
Interactions between folate derivatives and palladium(II) complexes are monitored in 1 : 1 molar ratio mixtures by circular dichroic spectra. The results are consistent with the following conclusions, i.e., tetrahydrofolate forms a chelate complex with palladium(II) through nitrogens 5 and 10 which is characterized by a unique circular dichroic spectrum. Mixtures of pallodium (II) complexes and dihydrofolate on methylenetetrahydrofolate could not be expected to, nor do they, give rise to similar circualr dichroic spectra for the following reasons: (1) The N5, N10 chelation site of tetrahydrofolate is blocked in methylenetetrahydrofolate, so coordination of a palladium(II) species must occur at some secondary site. (2) The N5, N10 chelation site is available but carbon six of the pteridine ring system is no longer asymmetric in dihydrofolate. Mixtures of dihdrofolate and palladium(II) complexes have no measurable circular dichroic spectra under the experimental conditions used.  相似文献   

16.
The dinuclear complexes [Pd2(L)2(bipy)2] (1), [Pd2(L)2(phen)2] (2), [Pt2(L)2(bipy)2] (3) and [Pt2(L)2(phen)2] (4), where bipy = 2,2′-bipyridine, phen = 1,10-phenanthroline and L = 2,2′-azanediyldibenzoic dianion) dibridged by H2L ligands have been synthesized and characterized. The binding of the complexes with fish sperm DNA (FS-DNA) were investigated by fluorescence spectroscopy. The results indicate that the four complexes bound to DNA with different binding affinity, in the order complex 4 > complex 3 > complex 2 > complex 1, and the complex 3 binds to DNA in both coordination and intercalative mode. Gel electrophoresis assay demonstrates the ability of the complexes to cleave the pBR 322 plasmid DNA. The cytotoxic activity of the complexes was tested against four different cancer cell lines. The four complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate.  相似文献   

17.
Four seven-coordinated manganese(II) complexes [Mn(tpa)(η1-NO3)(η2-NO3)] (1), [Mn(bpia)(η1-NO3)(η2-NO3)] (2), [Mn(tpa)(η1-NO3)(η2-NO3)] (3), [Mn(tpa)(η1-NO3)(η2-NO3)] (4), and one octacoordinated manganese(II) complex [Mn(bppza)(η2-NO3)2] (5) have been synthesized and characterized using the tripodal tetradentate ligands tpa, bpia, bipa, ipqa, and bppza (tpa: tris(2-pyridylmethyl)amine, bpia: bis(2-pyridylmethyl)(2-(N-methyl)imidazolylmethyl)amine, bipa: bis-(2-(N-methyl)imidazolylmethyl)(2-pyridylmethyl)amine, ipqa: (2-(N-methyl)imidazolylmethyl)(2-pyridylmethyl)(2-quinolylmethyl)amine, and bppza: bis(2-pyridylmethyl)(2-pyrazylmethyl)amine). The crystal structures for all compounds have been determined. 1, 2 and 3 crystallize in the triclinic space group , 4 crystallizes in the orthorhombic space group Pbca, whereas the eight-coordinated 5 crystallizes in the monoclinic space group P21/n. All compounds have one bidentate bound nitrate group in common. The coordination number and its geometry depend on the coordination mode of the second nitrate group. The coordination polyhedron for 1, 2, 3 and 4 is best described as an oblate octahedron and the one for 5 as a doubly oblate octahedron.  相似文献   

18.
Antitumor effects of a known bis(imino-quinolyl)palladium(II) complex 1 and its newly synthesized platinum(II) analogue 2 were evaluated against human breast (MCF-7) and human colon (HT-29) cancer cell lines. The complexes gave cytotoxicity profiles that were better than the reference drug cisplatin. The highest cytotoxic activities were pronounced in complex 2 across the two examined cancer cell lines. Both compounds represent potential active drugs based on bimetallic complexes.  相似文献   

19.
Two new coordination polymers [Cd(dps)2Cl2] (1) and [Co(dps)2(H2O)2]·(abs)2(H2O)2 (2) (dps = 4, 4′-dipyridylsulfide, Habs = 4-amino benzenesulfonic acid) have been synthesized under similar conditions and characterized by elemental analysis, fluorescence spectra and single crystal X-ray diffraction. Compound 1 displays a dps-bridged 2D puckered, grid-like layer, which is further linked by C-H?Cl hydrogen bonds to form a 3D supramolecular architecture. Compound 2 shows a dps-bridged double-stranded chain structure, which is extended by N-H?O and O-H?O hydrogen bonds generating a 3D network. Solid-state fluorescence results reveal that both complexes can emit strong emission bands, at 467 nm and 518 nm for 1 and 344 nm for 2, respectively. Magnetic measurements show that there are weak antiferromagnetic interactions between the adjacent Co(II) ions in 2.  相似文献   

20.
Complexes [Cu(HSas)(H2O)] · 2H2O (H3Sas = N-(2-hydroxybenzyl)-l-aspartic acid) (1), [Cu(HMeSglu)(H2O)] · 2H2O (H3MeSglu = (N-(2-hydroxy-5-methylbenzyl)-l-glutamic acid) (2), [Cu2(Smet)2] (H2Smet = (N-(2-hydroxybenzyl)-l-methionine) (3), [Ni(HSas)(H2O)] (4), [Ni2(Smet)2(H2O)2] (5), and [Ni(HSapg)2] (H2Sapg = (N-(2-hydroxybenzyl)-l-aspargine) (6) have been synthesized and characterized by chemical and spectroscopic methods. Structural determination by single crystal X-ray diffraction studies revealed 1D coordination polymeric structures in 2 and 4, and hydrogen-bonded network structure in 5 and 6. In contrast to previously reported coordination compounds with similar ligands, the phenol remains protonated and bonded to the metal ions in 2 and 4, and also probably in 1. However, the phenolic group is non-bonded in 6.  相似文献   

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