PREPARATION AND CHARACTERIZATION OF COBALT(III) COMPLEXES WITH SARCOSINE AND SOME TETRADENTATE LIGANDS OF THE EDDA TYPE

Abstract

Meridional geometrical isomers of cobalt(III) complexes with sarcosine (N-methylglycine) and tetradentate ligands edda (ethylenediamine-N,N′-diacetate ion), eddp (ethylenediamine-N,N′-di-3-propionate ion) and 1,3-pdda (1,3-propylenediamine-N,N′-diacetate ion) have been prepared. The edda and eddp cobalt(III) complexes were made by the reaction of sarcosine and sodium ethylenediamine-N,N′-diacetato(carbonato)cobaltate(III), and sodium uns-cis-(ethylenediamine-N,N′-di-3-propionato)(carbonato)cobaltate(III) dihydrate, respectively. The previously synthesized pdda-cobalt(III) complex with sarcosine was obtained by a new route by direct synthesis of cobalt(II) chloride hexahydrate with sarcosine and 1,3-pdda in the presents of lead(IV) oxide. Complexes were isolated chromatographically and characterized by elemental analysis, electron absorption spectra, infrared spectra and ¹H NMR spectroscopy.     

Synthesis and DNA binding studies of Ni(II), Co(II), Cu(II) and Zn(II) metal complexes of N1,N5-bis[pyridine-2-methylene]-thiocarbohydrazone Schiff-base ligand

The thiocarbohydrazone Schiff-base ligand with a nitrogen and sulphur donor was synthesized through condensation of pyridine-2-carbaldehyde and thiocarbohydrazide. Schiff-base ligands have the ability to conjugate with metal salts. A series of metal complexes with a general formula [MCl2(H2L)]·nH2O (MNi, Co, Cu and Zn) were synthesized by forming complexes of the N1,N5-bis[pyridine-2-methylene]-thiocarbohydrazone (H2L) Schiff-base ligand. These metal complexes and ligand were characterized by using ultraviolet-visible (UV-Vis), Fourier Transform Infrared (FT-IR), 1H and 13C NMR spectroscopy and mass spectroscopy, physicochemical characterization, CHNS and conductivity. The biological activity of the synthesized ligand was investigated by using Escherichia coli DNA as target. The DNA interaction of the synthesized ligand and complexes on E. coli plasmid DNA was investigated in the aqueous medium by UV-Vis spectroscopy and the binding constant (Kb) was calculated. The DNA binding studies showed that the metal complexes had an improved interaction due to trans-geometrical isomers of the complexes than ligand isomers in cis-positions.     

Substitution-Inert Metal Complex Mobile Phases in Non-Suppressed Cation Chromatography

Substitution-inert metal complexes, [Co(edda)(H₂O)₂]⁺, (Co(edda)(en)]⁺, [Co(edda)(dmen)]⁺, [Co(en)₂-(gly)]²⁺, [Co(en)₂(acac)]²⁺, and [Co(trien)(gly)]²⁺ in their nitrate salt solutions are used as eluents in nonsuppressed cation chromatography (where edda = ethylenediamine-N,N′-diacetic acid, en = ethylenediamine, dmen = N,N′-dime-thylethylenediamine, gly = glycine, acac = acetylacetone, and trien = triethylenetetraamine). It is found that all the mono- and di-valent charged complexes can be used to separate alkali and alkaline earth metal cations, respectively. The separations for monovalent cations are sometimes comparable to those using ultrapure HNO₃ solutions. However, the divalent Ca²⁺ and Sr²⁺ ions cannot be resolved using the metal complex eluents. On the other hand, a selected, direct non-suppressed IC separation of zinc(II) and cadmium(II) ions is demonstrated for the first time using a substitution-inert metal complex eluent and a conductivity detector. Comparisons of these eluents with those reported previously, i. e. HNO₃ and ethylenediammonium salt solution are made and explanations are proposed to account for the different selectivities observed where possible. The future development of this technique is also briefly discussed.     

氨·环己胺·羧酸根合铂(Ⅱ)类配合物的合成、抗肿瘤活性和与DNA的键合水平

本工作设计合成了6种新型氨·环己胺·羧酸根合铂!类配合物[Pt(NH3)(NH2)X2](a￣f)｛其中,X=CH3COO-(乙酸根),CH2ClCOO-(氯乙酸根),C6H5-COO-(苯甲酸根),p-CH3O-C6H4-COO-(对甲氧基苯甲酸根),p-CH3-C6H4-COO-(对甲基苯甲酸根),p-NO2-C6H4-COO-(对硝基苯甲酸根)｝。通过元素分析、摩尔电导、红外光谱、紫外光谱和1H核磁共振谱对配合物进行了表征。通过MTT法研究了配合物的体外抗肿瘤活性,通过流式细胞仪以及等离子体质谱研究了配合物对细胞周期的影响以及与细胞DNA的键合量;体外抗肿瘤活性测试表明,配合物(c￣f)对EJ和HL-602种肿瘤细胞表现出好的活性,而且配合物(c),(d)和(e)对EJ和HL-602种肿瘤细胞的活性高于临床用药顺铂;配合物(a￣f)对MCF-7、HCT-8和BGC-8233种肿瘤细胞的活性低于顺铂;它们能阻止HL-60和EJ细胞G2 M→G1期的进行;配合物(a￣f)与HL-60和EJ细胞的DNA键合量从大到小的顺序为:c>d>e>cisplatin>f>a>b。     

TCM active ingredient oxoglaucine metal complexes: crystal structure, cytotoxicity, and interaction with DNA

The alkaloid oxoglaucine (OG), which is a bioactive component from traditional Chinese medicine (TCM), was synthesized by a two-step reaction and used as the ligand to react with transition metal salts to give four complexes: [OGH][AuCl(4)]·DMSO (1), [Zn(OG)(2)(H(2)O)(2)](NO(3))(2) (2), [Co(OG)(2)(H(2)O)(2)](ClO(4))(2) (3), and [Mn(OG)(2)(H(2)O)(2)](ClO(4))(2) (4). The crystal structures of the metal complexes were confirmed by single crystal X-ray diffraction. Complex 1 is an ionic compound consisting of a charged ligand [OGH](+) and a gold complex [AuCl(4)](-). Complexes 2-4 all have similar structures (inner-spheres), that is, octahedral geometry with two OG coordinating to one metal center and two aqua ligands occupying the two apical positions of the octahedron, and two NO(3)(-) or ClO(4)(-) as counteranions in the outer-sphere. The complexation of OG to metal ion was confirmed by ESI-MS, capillary electrophoresis and fluorescence polarization. The in vitro cytotoxicity of these complexes toward a various tumor cell lines was assayed by the MTT method. The results showed that most of these metal-oxoglaucine complexes exhibited enhanced cytotoxicity compared with oxoglaucine and the corresponding metal salts, with IC(50) values ranging from 1.4 to 32.7 μM for sensitive cancer cells, which clearly implied a positive synergistic effect. Moreover, these complexes appeared to be selectively active against certain cell lines. The interactions of oxoglaucine and its metal complexes with DNA and topoisomerase I were investigated by UV-vis, fluorescence, CD spectroscopy, viscosity, and agarose gel electrophoresis, and the results indicated that these OG-metal complexes interact with DNA mainly via intercalation. Complexes 2-4 are metallointercalators, but complex 1 is not. These metal complexes could effectively inhibit topoisomerase I even at low concentration. Cell cycle analysis revealed that 1-3 caused S-phase cell arrest.     

NMR investigation of the interaction of vanadate with carbasilatranes in aqueous solutions

Reaction of vanadate with carbasilatranes [methoxy{N,N',N' '-2,2',3-[bis(1-methylethanolato)(propyl)]amino}silane (1), methoxy{N,N',N' '-2,2',3-[bis(1-ethanolethanolato)(propyl)]amino}silane (2), and {N,N',N' '-2,2',2-[bis(ethanolato)(glycolpropyl ether)]amino}silane (3)] in aqueous solution results in the formation of vanadosilicates and five-coordinated chelate vanadium(V) complexes as evidenced by 51V, 1H, and 13C NMR spectroscopy. Chiral carbasilatrane S,S-1 was characterized in the solid state by X-ray diffraction, revealing a trigonal bipyramidal geometry around the metal ion, with one unidentate methoxy group and one atrane nitrogen atom at the axial positions and one carbon and two atrane oxygen atoms at the equatorial plane of the bipyramid. Crystal data (Mo Kalpha; 100(2) K) are as follows: orthorhombic space group P2(1)2(1)2(1); a = 8.8751(6), b = 9.7031(7), c = 14.2263(12) A; Z = 4. The complexation of vanadium either with 1 or 2 is stereoselective yielding approximately 94% of the complex containing ligand in the S,R-configuration. The lower ability of the S,S- and R,R-diastereoisomers of 1 and 2 to ligate vanadate was attributed to stereochemical factors, dictating a square pyramidal geometry for the chelated complexes. A dynamic process between the vanadium chelate complexes and the respective carbasilatranes was evaluated by 2D {1H} EXSY NMR spectroscopy. These spectra show that the vanadate complexes with the open carbasilatranes exchange more slowly with the free ligand compared to the respective alcohol aminate complexes.     

Infrared multiple photon dissociation spectroscopy of cationized histidine: effects of metal cation size on gas-phase conformation

The gas phase structures of cationized histidine (His), including complexes with Li(+), Na(+), K(+), Rb(+), and Cs(+), are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy utilizing light generated by a free electron laser, in conjunction with quantum chemical calculations. To identify the structures present in the experimental studies, measured IRMPD spectra are compared to spectra calculated at B3LYP/6-311+G(d,p) (Li(+), Na(+), and K(+) complexes) and B3LYP/HW*/6-311+G(d,p) (Rb(+) and Cs(+) complexes) levels of theory, where HW* indicates that the Hay-Wadt effective core potential with additional polarization functions was used on the metals. Single point energy calculations were carried out at the B3LYP, B3P86, and MP2(full) levels using the 6-311+G(2d,2p) basis set. On the basis of these experiments and calculations, the only conformation that reproduces the IRMPD action spectra for the complexes of the smaller alkali metal cations, Li(+)(His) and Na(+)(His), is a charge-solvated, tridentate structure where the metal cation binds to the backbone carbonyl oxygen, backbone amino nitrogen, and nitrogen atom of the imidazole side chain, [CO,N(α),N(1)], in agreement with the predicted ground states of these complexes. Spectra of the larger alkali metal cation complexes, K(+)(His), Rb(+)(His), and Cs(+)(His), have very similar spectral features that are considerably more complex than the IRMPD spectra of Li(+)(His) and Na(+)(His). For these complexes, the bidentate [CO,N(1)] conformer in which the metal cation binds to the backbone carbonyl oxygen and nitrogen atom of the imidazole side chain is a dominant contributor, although features associated with the tridentate [CO,N(α),N(1)] conformer remain, and those for the [COOH] conformer are also clearly present. Theoretical results for Rb(+)(His) and Cs(+)(His) indicate that both [CO,N(1)] and [COOH] conformers are low-energy structures, with different levels of theory predicting different ground conformers.     

Homoleptic rare earth dipyridylamides [Ln2(N(NC5H4)2)6], Ln = Ce, Nd, Sm, Ho, Er, Tm, Yb, and Sc: metal oxidation by the amine melt and in 1,2,3,4-tetrahydroquinoline with the focus of different metal activation by amalgams, liquid ammonia, and microwaves

Homoleptic dimeric dipyridylamide complexes of the rare earth elements are obtained by solvent-free oxidation reactions of the metals with melts of 2,2'-dipyridylamine. As the thermal stabilities of the ligand as well as the amide complexes are limiting factors in these high-temperature syntheses, several different metal activation procedures have been investigated: the formation of Ln amalgams and dissolution of the metals in liquid ammonia as well as coupling to microwaves. For comparison with a solvent that shows low solubility of the metals and products, reactions in 1,2,3,4-tetrahydroquinoline were also carried out. For all lanthanides and group 3 metals used homoleptic dimers of the formula [Ln(2)(Dpa)(6)], Ln = Ce (1), Nd (2), Sm (3), Ho (4), Er (5), Tm (6), Yb (7), and Sc (8) and Dpa- = (C5H4N)2N-, were obtained, all containing trivalent rare earth ions with a distorted square antiprismatic nitrogen coordination. Due to the large differences in the ionic radii of the metal ions, two different structure types are found that crystallize in the space groups P2(1)/c and P2(1)/n with the border of the two types being between Tm and Yb. The orientations of two 1,3/1,3-double chelating and linking dipyridylamide ligands (Dpa(-) = (C(5)H(4)N)(2)N(-)) result in different overall orientations of the dimers and thus two structure types. All compounds were identified by single-crystal X-ray analysis. Mid-IR, far IR, and Raman spectroscopy, microanalyses, and simultaneous DTA/TG as well as mass spectrometry regarding their thermal behavior were also carried out to characterize the products. Crystal data for the two types follow. Ce (1): P2(1)/n; T = 170(2) K; a = 1063.0(1), b = 1536.0(1), c = 1652.0(2) pm; beta = 101.60(1) degrees ; V = 2642.2(3) x 10(6) pm(3); R(1) for F(o) > 4sigma(F(o)) = 0.046, wR(2) = 0.120. Sc (8): P2(1)/c; T = 170(2) K; a = 1073.0(1), b = 1506.2(2), c = 1619.8(2) pm; beta = 103.16(9) degrees ; V = 2548.9(5) x 10(6) pm(3); R(1) for F(o) > 4sigma(F(o)) = 0.038, wR(2) = 0.091.     

Synthesis, spectroscopy, thermal analysis, magnetic properties and biological activity studies of Co(II) and Co(II) complexes with Schiff base dye ligands

Three azo group-containing Schiff base ligands, namely 1-{3-[(3-hydroxypropylimino) methyl]-4-hydroxyphenylazo}-4-nitrobenzene (2a), 1-{3-[(3-hydroxypropylimino) methyl]-4-hydroxyphenylazo}-2-chloro-4-nitrobenzene (2b) and 1-{3-[(3-hydroxypropylimino) methyl]-4-hydroxyphenylazo}-4-chloro-3-nitrobenzene (2c) were prepared. The ligands were characterized by elemental analysis, FTIR spectroscopy, UV-Vis spectroscopy, 13C- and 1H-NMR spectroscopy and thermogravimetric analysis. Next the corresponding copper(II) and cobalt(II) metal complexes were synthesized and characterized by the physicochemical and spectroscopic methods of elemental analysis, FTIR spectroscopy, UV-Vis spectroscopy, magnetic moment measurements, and thermogravimetric analysis (TGA) and (DSC). The room temperature effective magnetic moments of complexes are 1.45, 1.56, 1.62, 2.16, 2.26 and 2.80 B.M. for complexes 3a, 3b, 3c, 4a 4b, and 4c, respectively, indicating that the complexes are paramagnetic with considerable electronic communication between the two metal centers.     

Spectroscopic,thermal, biological activity,molecular docking and density functional theoretical investigation of novel bis Schiff base complexes

New Schiff base ligand (H₂L, 1,2‐bis[(2‐(2‐hydroxyphenylimino)‐methyl)phenoxy]ethane) came from condensation reaction of bisaldehyde and 2‐aminophenol was synthesized in a molar ratio 1:2. Metal complexes and the ligand were completely discussed with spectroscopic and theoretical mechanism. The complexes with Fe(III), Cr(III), Mn(II), Co(II), Cu(II), Ni(II), Th(IV) and Zn(II) have been discussed and characterized by elemental analyses, molar conductance, IR, mass spectroscopy, thermal, magnetic measurements, and ¹H NMR. The results proved that the Schiff base was a divalent anion with hexadentate O₄N₂ donors came from the etheric oxygens (O1, O2), azomethine nitrogens (N1, N2) and deprotonated phenolic oxygens (O3, O4). Density Functional Theory using (B3LYP/6‐31G*) level of theory were implemented to predict molecular geometry, Mulliken atomic energetic and charges of the ligand and complexes. The calculation display that complexes had weak field ligand. The binding energy ranged from 650.5 to 1499.0 kcal/mol for Mn(II) and Th(IV) complexes, respectively. The biological behavior of the Schiff base ligand and its metal complexes were displayed against bacteria and fungi organisms. Fe(III) complex gave remarkable biological activity in comparison with the parent bis Schiff base.     

Synthesis,Characterization, DNA/HSA Interactions,and Anticancer Activity of Two Novel Copper(II) Complexes with 4-Chloro-3-Nitrobenzoic Acid Ligand

The purpose of this study was to identify new metal-based anticancer drugs; to this end, we synthesized two new copper(II) complexes, namely [Cu(ncba)₄(phen)] (1) and [Cu(ncba)₄(bpy)] (2), comprised 4-chloro-3-nitrobenzoic acid as the main ligand. The single-crystal XRD approach was employed to determine the copper(II) complex structures. Binding between these complexes and calf thymus DNA (CT-DNA) and human serum albumin (HSA) was explored by electronic absorption, fluorescence spectroscopy, and viscometry. Both complexes intercalatively bound CT-DNA and statically and spontaneously quenched DNA/HSA fluorescence. A CCK-8 assay revealed that complex 1 and complex 2 had substantial antiproliferative influences against human cancer cell lines. Moreover, complex 1 had greater antitumor efficacy than the positive control cisplatin. Flow cytometry assessment of the cell cycle demonstrated that these complexes arrested the HepG2 cell cycle and caused the accumulation of G0/G1-phase cells. The mechanism of cell death was elucidated by flow cytometry-based apoptosis assays. Western blotting revealed that both copper(II) complexes induced apoptosis by regulating the expression of the Bcl-2(Bcl-2, B cell lymphoma 2) protein family.     

Metal ion complexing properties of dipyridoacridine, a highly preorganized tridentate homologue of 1,10-phenanthroline

DPA (dipyrido[4,3-b;5,6-b]acridine) may be considered as a tridentate homologue of phen (1,10-phenanthroline). In this paper some of the metal ion complexing properties of DPA in aqueous solution are reported. Using UV-visible spectroscopy to follow the intense π-π* transitions of DPA as a function of pH gave protonation constants at ionic strength (μ) = 0 and 25 °C of pK(1) = 4.57(3) and pK(2) = 2.90(3). Titration of 10(-5) M solutions of DPA with a variety of metal ions gave log K(1) values as follows: Zn(II), 7.9(1); Cd(II), 8.1(1); Pb(II), 8.3(1); La(III), 5.23(7); Gd(III), 5.7(1); Ca(II), 3.68; all at 25 °C and μ = 0. Log K(1) values at μ = 0.1 were obtained for Mg(II), 0.7(1); Sr(II), 2.20(1); Ba(II), 1.5(1). The log K(1) values show that the high level of preorganization of DPA leads to complexes 3 log units more stable than the corresponding terpyridyl complexes for large metal ions such as La(III) or Ca(II), but that for small metal ions such as Mg(II) and Zn(II) such stabilization is minimal. Molecular mechanics calculations (MM) are used to show that the best-fit M-N length for coordination with DPA is 2.60 ?, accounting for the high stability of Ca(II) or La(III) complexes of DPA, which are found to have close to this M-N bond length in their phen complexes.     

A thiazole-containing tripodal ligand: synthesis, characterization, and interactions with metal ions and matrix metalloproteinases

A new tripodal ligand, tris[2-(((2-thiazolyl)methylidene)amino)ethyl]amine (Tatren), has been synthesized and characterized by NMR, IR, and UV-visible absorbance spectroscopy and elemental analysis. Tatren forms stable complexes with transition metal ions (Zn(2+), 1; Mn(2+), 2; Co(2+), 3) and the alkaline earth metal ions (Ca(2+), 4; Mg(2+), 5). Single-crystal X-ray structures of 1, 2, and 5 revealed six-coordinate chelate complexes with formula [M(Tatren)](ClO(4))(2) in which the metal centers are coordinated by three thiazolyl N atoms and three acyclic imine N atoms. Crystals of 1, 2, and 5 are monoclinic, P2(1)/c space group. Crystals of 4 are triclinic, P space group. The Ca(2+) complex is eight-coordinate with all N atoms of Tatren and one water molecule coordinated to the metal ion. Spectrophotometric titrations show that formation constants for the chelates of metal ions are >1 in methanol. Free Tatren inhibits the catalytic domain of matrix metalloproteinase-13 (MMP-13, collagenase-3) with K(i) = 3.5 +/- 0.6 microM. Molecular mechanics-based docking calculations suggest that one leg of Tatren coordinates to the catalytic Zn(2+) in MMPs-2, -9, and -13 with significant hydrogen bonding to backbone amide groups. High-level DFT calculations suggest that, in the absence of nonbonded interactions between Tatren and the enzyme, the most stable first coordination sphere of the catalytic Zn(2+) is achieved with three imidazolyl groups from His residues and two imine N atoms from one leg of Tatren. While complexes (1-3) do not inhibit MMP-13 to a significant extent, 4 does (K(i) = 30 +/- 10 microM). Hence, this study shows that tripodal chelating ligands of this class and their Ca(2+) complexes have potential as active-site inhibitors for MMPs.     

同、异双核卟啉-Salen型金属配合物的合成及非线性光学性质

设计合成了两种新型卟啉-Salen型配体5-(3-氨基-4-(3,5-二叔丁基水杨醛基)-氨基苯基)-10,15,20-三苯基卟啉(1)和5-(N,N'-二(3,5-二叔丁基水杨醛基)-3,4-二氨基苯基)-10,15,20-三苯基卟啉(2)及其同、异双核金属配合物和单金属核配合物.采用氢核磁共振(1H NHR)谱、电喷雾质谱(ESI-MS)、傅里叶变换红外(FTIR)光谱和紫外-可见(UV-Vis)光谱等手段对各目标化合物进行了表征.用Z扫描技术研究了配体及其金属配合物的三阶非线性光学性质.实验结果表明:配体1和配体2具有相似的光学特征,均具有反饱和吸收的特性和自散焦效应;当不同的金属离子嵌入配体形成单、双核金属配合物后,分子的极性发生改变,他们的光学特性均受到影响.     

Rare earth metal bis(amide) complexes bearing amidinate ancillary ligands: synthesis, characterization, and performance as catalyst precursors for cis-1,4 selective polymerization of isoprene

A family of rare earth metal bis(amide) complexes bearing monoanionic amidinate [RC(N-2,6-Me(2)C(6)H(3))(2)](-) (R = cyclohexyl (Cy), phenyl (Ph)) as ancillary ligands were synthesized and characterized. One-pot salt metathesis reaction of anhydrous LnCl(3) with one equivalent of amidinate lithium [RC(N-2,6-Me(2)C(6)H(3))(2)]Li, following the introduction of two equivalents of NaN(SiMe(3))(2) in THF at room temperature afforded the neutral and unsolvated mono(amidinate) rare earth metal bis(amide) complexes [RC(N-2,6-Me(2)C(6)H(3))(2)]Y[N(SiMe(3))(2)](2) (R = Cy (1); R = Ph (2)), and the "ate" mono(amidinate) rare earth metal bis(amide) complex [CyC(N-2,6-Me(2)C(6)H(3))(2)]Lu[N(SiMe(3))(2)](2)(μ-Cl)Li(THF)(3) (3) in 61-72% isolated yields. These complexes were characterized by elemental analysis, NMR spectroscopy, FT-IR spectroscopy, and X-ray single crystal diffraction. Single crystal structural determination revealed that the central metal in complexes 1 and 2 adopts a distorted tetrahedral geometry, and in complex 3 forms a distorted trigonal bipyramidal geometry. In the presence of AlMe(3), and in combination with one equimolar amount of [Ph(3)C][B(C(6)F(5))(4)], complexes 1 and 2 showed high activity towards isoprene polymerization to give high molecular weight polyisoprene (M(n) > 10(4)) with good cis-1,4 selectivity (>90%).     

Spacially confined M2 centers (M = Fe, Co, Ni, Zn) on a sterically bulky binucleating support: synthesis, structures and ethylene oligomerization studies

Two new bulky aryl-bridged pyridyl-imine compartmental (pro)ligands, 2,6-{(2,6-i-Pr(2)C6H3)N=C(Me)C5H3N}2C6H3Y (Y = H L1, OH L2-H), have been prepared in moderate to good overall yields via a Stille-type cross-coupling approach. The molecular structure of L2-H reveals a transoid configuration within the pyridyl-imine units with a hydrogen-bonding interaction maintaining the phenol coplanar with one of the adjacent pyridine rings. The interaction of 2 equiv of MX2 with L1 in n-BuOH at 110 degrees C gives the binuclear complexes, [(L1)M2X4] (M = Fe, X = Cl (1a); M = Co, X = Cl (1b); M = Ni, X = Br (1c); M = Zn, X = Cl (1d)), in which the metal centers adopt distorted tetrahedral geometries and occupy the two pyridyl-imine cavities in L1. In contrast, deprotonation of L2-H occurs upon reaction with 2 equiv of MX2 to afford the phenolate-bridged species [(L2)M2(mu-X)X2] (M = Fe, X = Cl (2a); M = Co, X = Cl (2b); M = Ni, X = Br (2c); M = Zn, X = Cl (2d)). 1H NMR studies of diamagnetic 1d and 2d reveal that the limited rotation of the N-aryl groups in 1d is further impeded in 2d by steric interactions imparted by the two closely located N-aryl groups. Partial displacement of the bridging bromide in 2c results upon its treatment with acetonitrile to afford [(L2)Ni2Br3(NCMe)] [2c(MeCN)]; no such reaction occurs for 2a, 2b, or 2d. Upon activation with excess methylalumoxane (MAO), 1b, 1c, 2b, and 2c show some activity for alkene oligomerization forming low molecular-weight materials with methyl-branched products predominating for the nickel systems. Single-crystal X-ray diffraction studies have been performed on L2-H, 1c, 2b, 2c, 2c(NCMe), and 2d.     

Anticancer and antimicrobial metallopharmaceutical agents based on palladium, gold, and silver N-heterocyclic carbene complexes

Complete synthetic, structural, and biomedical studies of two Pd complexes as well as Au and Ag complexes of 1-benzyl-3-tert-butylimidazol-2-ylidene are reported. Specifically, trans-[1-benzyl-3-tert-butylimidazol-2-ylidene]Pd(pyridine)Cl2 (1a) was synthesized from the reaction of 1-benzyl-3-tert-butylimidazolium chloride (1) with PdCl2 in the presence of K2CO3 as a base. The other palladium complex, [1-benzyl-3-tert-butylimidazol-2-ylidene]2PdCl2 (1b), and a gold complex, [1-benzyl-3-tert-butylimidazol-2-ylidene]AuCl (1c), were synthesized by following a transmetallation route from the silver complex, [1-benzyl-3-tert-butylimidazol-2-ylidene]AgCl (1d), by treatment with (COD)PdCl2 and (SMe2)AuCl, respectively. The silver complex 1d in turn was synthesized by the reaction of 1 with Ag2O. The molecular structures of 1a-d have been determined by X-ray diffraction studies. Biomedical studies revealed that, while the palladium complexes 1a and 1b displayed potent anticancer activity, the gold (1c) and silver (1d) complexes exhibited significant antimicrobial properties. Specifically, 1b showed strong antiproliferative activity against three types of human tumor cells, namely, cervical cancer (HeLa), breast cancer (MCF-7), and colon adenocarcinoma (HCT 116), in culture. The antiproliferative activity of 1b was found to be considerably stronger than that of cisplatin. The 1b complex inhibited tumor cell proliferation by arresting the cell cycle progression at the G2 phase, preventing the mitotic entry of the cell. We present evidence suggesting that the treated cells underwent programmed cell death through a p53-dependent pathway. Though both the gold (1c) and silver (1d) complexes showed antimicrobial activity toward Bacillus subtilis, 1c was found to be ca. 2 times more potent than 1d.     

(1,3-Dimethyluracil-5-yl)mercury(II): Preparative, Structural, and NMR Spectroscopic Studies of an Analog of CH(3)Hg(II)

The solution behavior of (1,3-DimeU-C5)Hg(CH(3)COO) (1a) (1,3-DimeU = 1,3-dimethyluracil) with regard to acetate replacement by anions X (Cl(-), Br(-), I(-), NO(3)(-), SCN(-), CN(-)) and by other model nucleobases (1-methylcytosine, 1-MeC, 1-methyluracil, 1-MeUH, 1-methylthymine, 1-MeTH, 9-ethylguanine, 9-EtGH, and 2-thiouracil, 2-ThioUH) has been studied, primarily by means of (1)H and (199)Hg NMR spectroscopy. Moreover, the bis(1,3-DimeU-C5) complex of Hg has been crystallized and studied by X-ray crystallography. 7a: orthorhombic system, space group Fdd2, a = 14.185(4) ?, b = 25.275(7) ?, c = 7.924(2) ?, V = 2840(2) ?(3), Z = 8. The acetato ligand of 1a is readily displaced by anions X, frequently followed by disproportionation reactions leading to HgX(2) and 7a. The donor atom X trans to C(5) has an effect on (3)J coupling between (199)Hg and H(6) of the 1,3-DimeU ligand according to NO(3)(-) > OAc(-) > Cl(-) approximately Br(-) > I(-) > SCN(-) > CN(-) > 1,3-DimeU-C5 with extremes being 222 (X = NO(3)(-)) and 107 Hz (7a). In the presence of excess metal ions (Ag(+), Hg(2+)), 1a forms hetero- and homonuclear derivatives with the second metal ion probably sitting at O(4). The mixed nucleobase complexes have the second base bound to Hg via N(3) (1-MeU (2a), 1-MeT (3a)), N(4) (1-MeC(-) (4a), 1-MeC (4b)), N(1) (9-EtG (5a)), N(7) (9-EtGH (5b)), and N(1), N(7) (9-EtG (5c)), as well as S(2) (2-ThioU (6a)). With the exception of the 9-ethylguanine complexes 5b and 5c, all the other complexes are inert on the (1)H time scale. In several cases, e.g. 2a, 3a, 4a, and 5a, formation of dinuclear Hg or heteronuclear Ag and Pt derivatives has been established by multinuclear NMR spectroscopy.     

Synthesis, structure, and spectroscopic and magnetic properties of mesomorphic octakis(hexylthio)-substituted phthalocyanine rare-earth metal sandwich complexes

The syntheses of new bis[octakis(hexylthio)phthalocyaninato] rare-earth metal(III) double-decker complexes [(C6S)8-Pc]2M (M = Gd(III), Dy(III), and Sm(III)) (2-4, respectively) are described. These compounds are very soluble in most common organic solvents. They have been fully characterized using elemental analysis, infrared, UV-vis spectroscopy, and mass spectrometry. The crystal structures of compounds 2-4 have been determined by X-ray diffraction on a single crystal. They are isostructural and crystallize in the monoclinic space group (space group C2/c). Their lattice constants have been determined in the following order: (2) a = 31.629(4) Angstroms, b = 32.861(4) Angstroms, c = 20.482(2) Angstroms, beta = 126.922(2) degrees, V = 17019(3) Angstroms(3); (3) a = 31.595(2) Angstroms, b = 32.816(2) Angstroms, c = 20.481(1) Angstroms, beta = 127.005(1) degrees, V = 16958(2) Angstroms(3); (4) a = 31.563(2) Angstroms, b = 32.796(2) Angstroms, c = 20.481(1) Angstroms, beta = 127.032 degrees, V = 16924(2) Angstroms(3). The magnetic properties of compounds 2-4 were studied, and it was revealed that the lanthanide ions and the radical delocalized on the two phthalocyanine rings are weakly interacting. The mesogenic properties of these new materials were studied by differential scanning calorimetry and optical microscopy. These phthalocyanine derivatives form columnar-hexagonal (Col(h)) mesophases. Thin films of bis[octakis(hexylthio)phthalocyaninato] rare-earth metal(III) double-decker complexes (2-4) were prepared by a spin-coating technique. Thermally induced molecular reorganization within films of bis[octakis(hexylthio)phthalocyaninato] rare-earth metal(III) double-decker complexes (2-4) was studied by the methods of ellipsometry, UV-vis absorption spectroscopy, and atomic force microscopy. Heat treatment produces molecular ordering, which is believed to be due to stacking interaction between neighboring phthalocyanine moieties.     

Synthesis and characterization of novel Pd(II) complexes with chelating and non-chelating heterocyclic iminocarbene ligands

The imidazolium salts [3-R1-1-{2-Ar-imino)-2-R2-ethyl}imidazolium] chloride (C-N; Ar = 2,6-iPr2C6H3; R1/R2 = Me/Me (a), Me/Ph (b), Ph/Me (c), 2,4,6-Me3C6H2 (d), 2,6-iPr2C6H3 (e)) react with Ag(2)O to give Ag(I) iminocarbene complexes (C-N)AgCl (4a-e) in which the iminocarbene ligand is bonded to Ag via the imidazoline-2-ylidene carbon atom. The solid-state structures of 4b and 4d were determined by X-ray crystallography and revealed the presence of monomeric (carbene)AgCl units with Z and E configurations at the imine C=N bonds, respectively. Carbene transfer to Pd occurs when compounds 4b-e are treated with (COD)PdCl2 to yield bis(carbene) complexes (C-N)2PdCl2 (6b-e) containing two kappa1-C bonded iminocarbene moieties. NMR spectroscopic data indicated a trans coordination geometry at Pd. This conclusion was supported by an X-ray structure determination of 6b which clearly demonstrated the non-chelating nature of the iminocarbene ligand system. EXSY 1H NMR spectroscopy suggests that the non-chelating structures undergo E/Z isomerization at the imine C[double bond, length as m-dash]N double bonds in solution. The preparative results contrast our earlier report that the reaction between 4a and (COD)PdCl2 results in a chelating kappa2-C,N bonded iminocarbene complex (C-N)PdCl2. The coordination mode and dynamic behavior of the iminocarbene ligand systems have been found to be dramatically affected by changes in the substitution pattern of the ligand system. Sterically unencumbered systems (a) favor the formation of kappa2-C,N chelate structures containing one iminocarbene moiety per metal upon coordination at Pd(II); these complexes were demonstrated to engage in reversible, solvent-mediated chelate ring-opening reactions. Sterically encumbered systems (b-e) form non-chelating kappa1-C iminocarbene Pd(II) complexes containing two iminocarbene ligands per metal. Transannular repulsions across the chelate ring are believed to be the origin of these structural differences.