Metal ion-biomolecule interactions. III. Versatility of metal ion binding to imidazoles. Synthesis and 1H nmr spectroscopic properties of N- and C-bound mercury(II) complexes

Methylmercury(II) and mercury(II) complexes of imidazole (1), 1-methylimidazole (2), and the 1,3-dimethylimidazolium ion (3) have been prepared in aqueous or ethanolic solution. Elemental analysis and ¹H nmr spectroscopy have been used to characterize the complexes. The MeHg (Me = methyl) binding sites have been identified as N₁, N₃ (1), N₃, C₂ (2), and C₂ (3). Reaction with HgO leads to the formation of Hg-bridged complexes of the type Im-Hg-Im, (Im = imidazole), where bonding occurs through N₁ (1) and C₂ (3); the latter is also formed as a result of symmetrization of the C₂-bound MeHg complex. The formation of the C₂-bound (carbene) complexes is discussed in terms of the increased acidity of the C₂ proton resulting from coordination of an electrophilic species at N₃. Based on electrostatic considerations, there appears to be a “minimum degree of activation” required before C₂ bonding can occur, which explains the lack of this coordination mode in 1. ¹⁹⁹Hg-¹H spin-spin coupling (⁴J) is observed for C-bound mercury, but not for N-bound mercury, which is interpreted in terms of a decreased ligand exchange rate in the former case, due to the greater stability of the Hg-C bond. ²J coupling constants measured in (CD₃)₂SO for a number of MeHg complexes of heterocyclic ligands (including the imidazoles of the present study) correlate well with the ligand pK_a (25°C, aqueous solution), according to ²J = ?3.88 pK_a + 248.5. Results in the present work are discussed in relation to our previous work with nucleosides. The significance of the results to biological systems is considered.     

Synthesis,characterization and bioactivity of four novel trinuclear copper(II) and nickel(II) complexes with pentadentate ligands derived from N-acylsalicylhydrazide

Four novel trinuclear copper(II)/nickel(II) complexes with four trianionic pentadentate ligands, N-(3-t-butylbenzoyl)-5-nitrosalicylhydrazide (H₃3-t-bbznshz), N-(3,5-dimethylbenzoyl)salicylhydrazide (H₃3,5-dmbzshz), N-(phenylacetyl)-5-bromosalicylhydrazide (H₃pabshz) and N-(3-t-butylbenzoyl)salicylhydrazide (H₃3-t-bbzshz) have been synthesized and characterized by X-ray crystallography. These trinuclear compounds all have an M–N–N–M–N–N–M core formed by three metal ions and two ligands. The geometries of three Cu(II) ions in compound Cu₃(3-t-bbznshz)₂(H₂O)(DMF)(py)₂ · DMF (1) alternate between distorted square pyramidal and square planar, while in compound Cu₃(3,5-dmbzshz)₂(py)₂ (2), they are all square planar. Three Ni(II) ions in compound Ni₃(pabshz)₂(DMF)₂(py)₂ (3) and Ni₃(3-t-bbzshz)₂(py)₄ · 2H₂O (4) follow square-planar/octahedral/square-planar coordination geometry. Compounds 1, 2 and 4 are bent trinuclear, with the bend angles of 156.4°, 141.49° and 127.1°, respectively, while the three nickel ions in compound 3 are strictly linear, with an angle of 180°. Studies on the trinuclear Ni(II) complexes show that the β-branched N-acylsalicylhydrazide ligands with sterically flexible Cα methylene groups are easier to yield linear trinuclear Ni(II) complexes, while α-branched N-acylsalicylhydrazides ligands tend to form bent trinuclear Ni(II) complexes. Antibacterial screening data indicate that the trinuclear Cu(II) compound 2 is more active than 1 and mononuclear Cu(II) compound, bent trinuclear Ni(II) compound 4 is more active than linear compound 3 and less active than tetranuclear nickel compound in the previous study.     

In vitro anti-proliferative,and in silico ribonucleotide reductase and pharmacokinetics studies of heteroleptic silver(I), nickel(II) and copper(II) complexes of 4-methyl-3-thiosemicarbazones and ibuprofen

ObjectivesThe present research focuses on the in vitro anti-proliferative, and in silico ribonucleotide reductase and pharmacokinetics studies of twelve heteroleptic metal complexes of the general formulae [Ag(L¹⁻⁴)(ibu)] (1–4) and [M(L¹⁻⁴)(ibu)₂] (5–12), where L¹⁻⁴ = 2-(1-(4-substitutedphenyl)ethylidene)-N-methylhydrazinecarbothioamide, ibu = non-steroidal anti-inflammatory drug (ibuprofen), and M = Cu(II) and Ni(II).MethodsVarious spectroscopic techniques were used to authenticate the structure of the synthesized complexes. UV-Vis and cyclic voltammetry techniques were used to analyse the stability and the reducing ability of the complexes. In vitro anti-proliferative studies by MTT assay, apoptotic behaviour and cellular uptake studies were investigated followed by the in silico interaction with ribonucleotide reductase (RNR) enzyme.ResultsThe spectral studies predicted distorted tetrahedral geometry around silver(I) ion and distorted octahedral geometry around nickel(II) and copper(II) ions. The reducing ability of the copper(II) complexes was analysed using ascorbic acid by UV-Vis and cyclic voltammetry techniques, which authenticate the reducing ability of the complexes and the possible interactions within the cells. The in vitro anti-proliferative activity of the synthesized complexes against three cancerous (estrogen positive (MCF-7), estrogen negative (MDA-MB-231) and pancreatic (PANC-1)) and one normal (MCF-10a) cell lines by MTT assay showed enhanced activity for copper(II) complexes 11 and 12 containing the hydrophobic substituents. The apoptotic and cellular uptake studies showed that the complex 12 is readily taken up by PANC-1 cell lines and induces ROS-mediated mitochondrial and caspase-dependent apoptosis. The in silico studies indicated hydrogen bonding, hydrophobic and π-pair (π–π, π–σ and π–cation) interactions between the complexes and the ribonucleotide reductase (RNR) enzyme. The in silico pharmacokinetics studies of the complexes predicted the drug-likeness characteristics of the complexes.ConclusionThe synthesized complexes are found to be less toxic to normal cells and inhibit the growth of cancerous cells by inducing mitochondrial-mediated and caspase dependent apoptotic pathway in PANC-1 cells.     

N-(3,5-Dichloro-4-(2,4,6-trichlorophenoxy)phenyl)benzenesulfonamide: A new dual-target inhibitor of mitochondrial complex II and complex III via structural simplification

Mitochondrial complex II and complex III are two promising targets for the development of numerous pharmaceuticals and pesticides. Although tremendous inhibitors of either complex II or complex III were identified, compounds which are capable of prohibiting the activities of both complexes have been rarely reported. Since multi-target drugs can interact with several drug targets simultaneously, we were keen on discovering new and potent dual-target inhibitors of both complex II and complex III. Therefore, a new series of structurally simplified sulfonamides bearing a diaryl ether scaffold were designed and synthesized in this paper. Afterwards, the biological activities of the newly synthesized compounds were evaluated. The results implied that several compounds demonstrated outstanding potency against succinate-cytochrome c reductase (SCR, a mixture of complex II and complex III). Further studies confirmed that N-(3,5-Dichloro-4-(2,4,6-trichlorophenoxy)phenyl)benzenesulfonamide (3f), a representative compound herein, was identified as a dual-target inhibitor of both complexes. Furthermore, computational simulations were also performed to have a better understanding about binding of 3f to the enzyme complexes, which concluded that 3f should bind to complex II and the Q_o site of complex III. Consequently, we harbor the idea that this work can be beneficial for the synthesis and discovery of more dual- or multi-target inhibitors.     

Biomimetic zinc(II) and cobalt(II) complexes with tri-tert-butoxysilanethiolate and imidazole ligands - Structural and spectroscopic studies

New, heteroleptic zinc and cobalt complexes with tri-tert-butoxysilanethiolate and imidazole co-ligands are characterized by crystal structure studies. The ligands exhibit different coordination modes to Co(II) ions: NOS₂ (with methanol as O-donor ligand) in 2′, NO₂S₂ in 2′′, N₂S₂ in 1, and to Zn(II) ions: N₂S₂ in 3 and N₃S in 4. Complex 2′ is a structural analog of cobalt-substituted active site of alcohol dehydrogenase. All four-coordinate Co(II) and Zn(II) complexes have tetrahedral geometry. Solution and solid state electronic spectra of cobalt(II) complexes are discussed and compared to literature data available for the cobalt-substituted liver alcohol dehydrogenase and sorbitol dehydrogenase. The EPR spectra of all cobalt complexes exhibit at 77 K a characteristic broad signal with g ∼3.6 and 5.6, strongly indicating a high-spin state, S = 3/2, of Co(II) complexes.     

Redox cycling of iron complexes of N-(dithiocarboxy)sarcosine and N-methyl-d-glucamine dithiocarbamate

Iron(II)–dithiocarbamate complexes are used to trap nitrogen monoxide in biological samples, and the resulting nitrosyliron(II)–dithiocarbamate is detected and quantified by ESR. As the chemical properties of these compounds have been little studied, we investigated whether iron dithiocarbamate complexes can redox cycle. The electrode potentials of iron complexes of N-(dithiocarboxy)sarcosine (dtcs) and N-methyl-d-glucamine dithiocarbamate (mgd) are 56 and −25 mV at pH 7.4, respectively, as measured by cyclic voltammetry. The autoxidation and Fenton reaction of iron(II)–dtcs and iron(II)–mgd were studied by stopped-flow spectrophotometry with both iron(II) complexes and dioxygen or hydrogen peroxide in excess. In the case of excess iron(II)–dtcs and –mgd complexes, the rate constants of the autoxidation and the Fenton reaction are (1.6–3.2) × 10⁴ and (0.7–1.1) × 10⁵ M⁻¹ s⁻¹, respectively. In the presence of nitrogen monoxide, the oxidation of iron(II)–dtcs and iron(II)–mgd by hydrogen peroxide is significantly slower (ca. 10–15 M⁻¹ s⁻¹). The physiological reductants ascorbate, cysteine, and glutathione efficiently reduce iron(III)–dtcs and iron(III)–mgd. Therefore, iron bound to dtcs and mgd can redox cycle between iron(II) and iron(III). The ligands dtcs and mgd are slowly oxidized by hydrogen peroxide with rate constants of 5.0 and 3.8 M⁻¹ s⁻¹, respectively.     

Synthesis, crystal structure, cytotoxic activities and DNA-binding properties of new binuclear copper(II) complexes bridged by N,N′-bis(N-hydroxyethylaminoethyl)oxamide

Two new μ-oxamido-bridged binuclear copper(II) complexes with formulae of [Cu₂(heae)(pic)₂] (1) and [Cu₂(heae)(Me₂phen)₂](ClO₄)₂ · H₂O (2), where heae and pic stand for the anion of N,N′-bis(N-hydroxyethylaminoethyl)oxamide and 2,4,6-trinitrophenol, respectively, and Me₂phen represents 2,9-dimethyl-1,10-phenanthroline; have been synthesized and characterized by elemental analyses, molar conductivity measurements, IR and electronic spectra studies. The crystal structures of the two binuclear copper(II) complexes have been determined by X-ray single-crystal diffraction. In both the two binuclear complexes the central two copper(II) atoms are bridged by trans-heae. In complex 1 the coordination environment around each copper(II) atom can be described as a distorted octahedral geometry, while in complex 2 each copper(II) atom displays a square-pyramid stereochemistry. Hydrogen bonding and π-π stacking interactions link the binuclear copper(II) complex 1 or 2 into a 3D infinite network. The cytotoxicities of the two binuclear copper(II) complexes were tested by Sulforhodamine B (SRB) assays against human hepatocellular carcinoma cell SMMC-7721 and human lung adenocarcinoma cell A549. Both of the two binuclear copper(II) complexes exhibit potent cytotoxic effects against SMMC-7721 and A549 cell lines. The interactions of the two binuclear complexes with herring sperm DNA (HS-DNA) are investigated by using absorption and emission spectra and electrochemical techniques and viscometry. The results suggest that both the two binuclear copper(II) complexes interact with HS-DNA in the mode of intercalation with the intrinsic binding constants of 1.73 × 10⁵ M⁻¹ (1) and 1.92 × 10⁶ M⁻¹ (2). The influence of structural variation of the terminal ligands in the binuclear complexes on DNA-binding properties is preliminarily discussed.     

Synthesis,structural characterization and cell death-inducing effect of novel palladium(II) and platinum(II) saccharinate complexes with 2-(hydroxymethyl)pyridine and 2-(2-hydroxyethyl)pyridine on cancer cells in vitro

Four palladium(II) and platinum(II) saccharinate (sac) complexes with 2-(hydroxymethyl)pyridine (2-hmpy) and 2-(2-hydroxyethyl)pyridine (2-hepy), namely trans-[Pd(2-hmpy)₂(sac)₂]·H₂O (1), trans-[Pt(2-hmpy)₂(sac)₂]·3H₂O (2), trans-[Pd(2-hepy)₂(sac)₂] (3) and trans-[Pt(2-hepy)₂(sac)₂] (4), have been synthesized and characterized by elemental analysis, UV–vis, IR and NMR. Single crystal X-ray analysis reveals that the metal(II) ions in each complex are coordinated by two sac and two 2-hmpy or 2-hepy ligands with a trans arrangement. Anticancer effects of 1–4 were tested against four different cancer cell lines (A549 and PC3 for lung cancer, C6 for glioblastoma, and Hep3B for liver cancer). Cytotoxicity was first screened by the MTT assay and the results were further confirmed by the ATP assay. The mode of cell death was determined by both histological and biochemical methods. Among the metal complexes, complex 2 resulted in relatively stronger anti-growth effect in a dose-dependent manner (3.13–200 μM), compared to the others, by inducing apoptosis.     

Dinuclear and mononuclear copper(II) carboxylate complexes with cis-chelating diacids

The synthesis and crystal structures of two new copper complexes with chelating dicarboxylic acids are described. Reaction of copper(II) acetate with diacid H₂L2 (HO₂CC(Me)₂OArOC(Me)₂CO₂H, Ar=1,3-substituted phenyl) gave a bischelate complex (L2)₂Cu₂ · 2MeOH with the normal paddlewheel structure and tilted, trans-oriented chelate rings with skewed conformations. The overall structure was reasonably well reproduced by density functional calculations on (L2)₂Cu₂. Treatment of the product from reaction of Cu₂(OAc)₄ and diacid H₂L3 (Ar=1,3-substituted 2,4-dibromophenyl) with pyridine gave a six-coordinate mononuclear chelate (L3)Py₂Cu · H₂O in which one chelate carboxylate is monodentate, the other is unsymmetrically bidentate, and the pyridines are cis-coordinated.     

Syntheses and structures of photochromic molybdenum(II) and rhodium(II) complexes with 1,2-dicyano-1,2-bis(2,4,5-trimethyl-3-thienyl)ethene

Four novel Mo(II) and Rh(II) complexes with cis-1,2-dicyano-1,2-bis(2,4,5-trimethyl-3-thienyl)ethene (cis-dbe) or closed-dbe were synthesized and characterized. Employing [M(O₂CCF₃)₄] (M = Mo, Rh) with cis-dbe or closed-dbe afforded complex [Mo₂(O₂CCF₃)₄(cis-dbe)](benzene) (1), [Rh₂(O₂CCF₃)₄(cis-dbe)](benzene) (2), [{Mo₂(O₂CCF₃)₄}₂(closed-dbe)] (3), and [Rh₂(O₂CCF₃)₄(closed-dbe)](p-xylene) (4). The structures of four metal complexes were revealed by X-ray crystallographic analyses and the correlation between the crystal structures and the photochromic performance was discussed. In all complexes, two cyano groups of the ligand bridged two dimetal carboxylates to give a 1-D zigzag infinite chain structure. Upon irradiation with 405 nm light, complex 1 turned into reddish purple from yellow, and the color reverted to initial yellow on exposure to 563 nm light, indicating the reversible cyclization/ring-opening reaction in the crystalline phase. However, the Rh(II) complex 2 did not display similarities in reaction induced by light, which is attributable to the lower ratio of photoactive anti-parallel conformers compared with complex 1 and coordination effect of metal ions on photochromism of diarylethenes. The complexes of Rh(II) ions did not exhibit the expected reversible photoinduced behavior.     

Preparation and characterization of (9-methyladenine)triammineplatinum(II) and trans-dihydroxo(9-methyladenine)triammineplatinum(IV) complexes

The preparation is reported of [(NH₃)₃Pt(9- MeA)] X₂ (9-MeA = 9-methyladenine) with XCl (1a) and XClO₄ (1b) and of trans-[(OH)₂Pt(NH₃)₃- (9-MeA)]X₂ with XCl (2a) and XClO₄ (2b), and the crystal structure of 1b. [(NH₃)₃Pt(C₆H₇N₅)](ClO₄)₂ crystallizes in space group P2₁/n with a = 20.810(7) Å, b = 7.697(3) Å, c = 10.567(4) Å, β = 91.57(6)°, Z = 4. The structure was refined to R = 0.054, R_w = 0.063. In all four compounds Pt coordination is through N7 of 9-MeA, as is evident from ³J coupling between H8 of the adenine ring and ¹⁹⁵Pt. Pt(II) and Pt(IV) complexes can be differentiated on the basis of different ³J values, larger for Pt(II) than for Pt(IV) by a factor of 1.57 (av). In Me₂SO-d₆, hydrogen bonding occurs between Cl^? and C(8)H of 9-MeA as weil as between Cl^? and the NH₃ groups in the case of the Pt(II) complex 1a. Protonation of the 9-MeA ligands was followed using ¹H NMR spectroscopy and pK_a values for the N1 protonated 9-MeA ligands were determined in D₂O. They are 1.9 for 1a and 1.8 for 2a, which compares with 4.5 for the non-platinated 9-MeA. Possible consequences for hydrogen bonding with the complementary bases thymine or uracil are discussed briefly. Protonation of the OH groups in the Pt(IV) complexes has been shown not to occur above pH 1.     

New insight in coordination of vic-dioximes: Bis- and tris(E,E-dioximato)Ni(II) complexes

N,N′-Bis[allylamino]glyoxime, N,N′-bis[anilino]glyoxime, and N,N′-bis[1,2,3,4-tetrahydro-5-naphthalenamino]glyoxime have been prepared from corresponding amines and (E,E)-dichloroglyoxime. These ligands gave orange-red compound with NiCl₂ in less acidic medium (pH ∼ 5) that are bis(E,E-dioximato)nickel(II) complexes {[(E,E)-Ni(HL)₂]} (1a-3a) and green compounds in acidic medium (pH ∼ 2) that are tris(E,E-dioximato)nickel(II) dichloride complexes {[(E,E)-Ni(LH₂)₃]Cl₂} (1b-3b). The crystal structures of all complexes have been determined by X-ray diffraction on a single crystal. The study of absorption spectra of these two types of complexes shows that they may be converted to each other by addition of acids (1a-3a) or bases (1b-3b) and there is no way for the amphi form.     

Platinum(II) complexes with aryl tellurols and diaryl ditellurides: Syntheses and spectral investigations

Arytellurol complexes [PtCl(TeAr)(PPh₃)₂] (I) and [Pt(TeAr)₂(PPh₃)₂] (II) are readily obtained from cis-[PtCl₂(PPh)₃)₂] and NaTeAr (Ar = C₆H₅, 4-CH₃OC₆H₄ and 4-CH₃CH₂OC₆H₄) in ethanolbenzene at room temperature. ³¹P NMR spectra of (I) and (II) indicate their trans configuration in solution. Metathetical reactions between I (Ar = 4-CH₃OC₆H₄) and NaX (X = I, Br, SCN) occur in methanol to give [Pt(X)(TeC₆H₄OCH₃-4)(PPh₃)₂]. ¹H NMR shows that equimolar proportions of NaTeC₆H₅, NaTeC₆H₄OCH₂CH₃-4 and cis-[PtCl₂(PPh₃)₂] give a mixture of three complexes: II, Ar = C₆H₅; II, Ar = 4-CH₃CH₂OC₆H₄; and [Pt(TeC₆H₅)(TeC₆H₄OCH₂CH₃-4)(PPh₃)₂]. Polymeric complexes [PtCl(TeAr)]_n (III) and [Pt(TeAr)₂]_n (IV) result from reaction between K₂[PtCl₄] and NaTeAr in aqueaous ethanol. They react with excess of PPh₃ in CDCl₃ to yield monomeric complexes I and II respectively which were characterized in situ by ¹H and ³¹P NMR of the reaction mixtures. IR spectra indicate the presence of bridging chloride ligands in III. An alternating chloride and tellurol bridged chain structure for III and a tellurol bridged for IV have been proposed. Reaction between equimolar amounts of III and PPh₃ in dichloromethane yielded a tellurol bridged dimeric complex [PtCl(μ-TeAr)(PPh₃)]₂ (V) with terminal chloride ligand as suggested by IR study. Ethanolic solutions of diarylditellurides also react readily with an aqueous solution of K₂[PtCl₄] at 10 °C to give complexes for which the structure trans-[PtCl₂(ArTeTeAr)₂] (VI) is suggested from their elemental analyses, IR, Raman (in one case only), ¹H, ¹²⁵Te (in one case only), and ¹⁹⁵Pt NMR spectra and reactions with triphenylphosphine which liberated free ditellurides. At 40 °C or above the same ditellurides form polymeric complexes III with K₂[PtCl₄] in aquaeous ethanol.     

Synthesis, crystal structures, DNA-binding properties, cytotoxic and antioxidation activities of several new ternary copper(II) complexes of N,N′-(p-xylylene)di-alanine acid and 1,10-phenanthroline

Three novel ternary copper(II) complexes, [Cu₂(phen)₂(l-PDIAla)(H₂O)₂](ClO₄)₂·2.5H₂O (1), [Cu₄(phen)₆(d,l-PDIAla)(H₂O)₂](ClO₄)₆·3H₂O (2) and [Cu₂(phen)₂(d,l-PDIAla)(H₂O)](ClO₄)₂·0.5H₂O (3) (phen = 1,10-phenanthroline, H₂PDIAla = N,N’-(p-xylylene)di-alanine acid) have been synthesized and structurally characterized by single-crystal X-ray crystallography and other structural analysis. Spectrometric titrations, ethidium bromide displacement experiments, CD (circular dichroism) spectral analysis and viscosity measurements indicate that the three compounds, especially the complex 3, strongly bind to calf-thymus DNA (CT-DNA). The intrinsic binding constants of the ternary copper(II) complexes with CT-DNA are 0.89 × 10⁵, 1.14 × 10⁵ and 1.72 × 10⁵ M⁻¹, for 1, 2 and 3, respectively. Comparative cytotoxic activities of the copper(II) complexes are also determined by acid phosphatase assay. The results show that the ternary copper(II) complexes have significant cytotoxic activity against the HeLa (Cervical cancer), HepG2 (hepatocarcinoma), HL-60 cells (myeloid leukemia), A-549 cells (pulmonary carcinoma) and L02 (liver cells). Investigations of antioxidation properties show that all the copper(II) complexes have strong scavenging effects for hydroxyl radicals and superoxide radicals.     

Syntheses, structures and bioactivities of cadmium(II) complexes with a tridentate heterocyclic N- and S-ligand

Four cadmium(II) complexes of the semirigid tridentate ligand 8-[(pyridin-4-yl)methylthio] quinoline (TQMP4, L), namely, [CdL₂](ClO₄)₂ (1), [Cd(L)Br₂] (2), [Cd₂(L)₂(NO₃)₄] (3), and [Cd₂(L)₂I₄] (4), have been prepared by the methods of layering and the diffusing of diethyl ether. The structures of the complexes have been identified by elemental analysis (EA), infrared spectra (IR) and single-crystal diffraction. The different coordination modes of the ligands and counter anions result in a 2D (4, 4) net structure in complex 1, a 1D polymer chain in complex 2, and 0D binuclear rings in complexes 3 and 4. Their antibacterial and antifungal activities were also tested.     

Synthesis, X-ray structures, electrochemical properties and cytotoxic effects of Co(II) complexes

1-Benzothiazol-2-yl-3,5-dimethyl-1H-pyrazole (1a) and 1-benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester (1b) were reacted with the hexahydrates of cobalt(II) chloride, cobalt(II) nitrate and cobalt(II) perchlorate to give the corresponding complexes 2a-4a and 2b-5b, respectively. Obtained compounds differ in coordination spheres of central atoms. The complex 2a includes a fivefold coordinated cobalt(II) ion, whereas 3a shows a distorted octahedral configuration around the cobalt(II) ion. All complexes were characterised by FTIR spectroscopy, MS and elemental analysis. The X-ray structures of 2a, 3a and 5b complexes were also solved. The cytotoxic properties of the ligand 1a and both series of Co(II) complexes were examined on human leukemia NALM-6 and HL-60 cells and melanoma WM-115 cells. The ligands, were found to have very low cytotoxicity. Complex 3b exhibited the highest cytotoxic activity with IC₅₀ values in the range of 6.9-17.1 μM for three examined cell lines.     

Synthesis and characterization of new ruthenium(II) complexes containing coupled di(2-pyridyl) and 1,3-dithiole units

Two new ruthenium (II) complexes containing coupled di(2-pyridyl) and 1,3-dithiole units, cis-[Ru(Medpydt)₂(NCS)₂] (2, Medpydt = dimethyl 2-(di(2-pyridyl)methylene)-1,3-dithiole-4,5-dicarboxylate) and cis-[Ru(H₂dpydt)₂(NCS)₂] (3, H₂dpydt = 2-(di(2-pyridyl)methylene)-1,3-dithiole-4,5-dicarboxylate), have been synthesized and characterized. The structure of complex 2 has been determined by X-ray crystallography. There exist intermolecular H-bonding interactions between carbomethoxy groups on neighboring pyridine rings giving rise to 2D H-bonded arrays. The metal-to-ligand charge-transfer (MLCT) absorptions were observed around 480 nm. Redox properties of ruthenium complexes have been investigated by cyclic voltammetry. Solar cells involving thin films of anatase TiO₂ impregnated with cis-[Ru(H₂dpydt)₂(NCS)₂] were prepared, and the photovoltaic performance was preliminarily investigated.     

Olefin aziridination by copper(II) complexes: Effect of redox potential on catalytic activity

A series of new copper(II) complexes of four sterically hindering linear tridentate 3N ligands N′-ethyl-N′-(pyrid-2-ylmethyl)-N,N-dimethylethylenediamine (L1), N′-benzyl-N′-(pyrid-2-ylmethyl)-N,N-dimethylethylenediamine (L2), N′-benzyl-N′-(6-methylpyrid-2-yl-methyl)-N,N-dimethylethylenediamine (L3) and N′-benzyl-N′-(quinol-2-ylmethyl)-N,N-dimethylethylenediamine (L4) have been isolated and examined as catalysts for olefin aziridination. The complexes [Cu(L1)Cl₂]·CH₃OH 1, [Cu(L2)Cl₂]·CH₃OH 2, [Cu(L3)Cl₂]·0.5 H₂O 3 and [Cu(L4)Cl₂] 4 have been structurally characterized by X-ray crystallography. In all of them copper(II) adopts a slightly distorted square pyramidal geometry as inferred from the values of trigonality index (τ) for them (τ: 1, 0.02; 2, 0.01; 3, 0.07; 4, 0.01). Electronic and EPR spectral studies reveal that the complexes retain square-based geometry in solution also. The complexes undergo quasireversible Cu(II)/Cu(I) redox behavior (E_1/2, −0.272 − −0.454 V) in acetonitrile solution. The ability of the complexes to mediate nitrene transfer from PhINTs and chloramine-T trihydrate to olefins to form N-tosylaziridines has been studied. The complexes 3 and 4 catalyze the aziridination of styrene very slowly yielding above 80% of the desired product. They also catalyze the aziridination of the less reactive olefins like cyclooctene and n-hexene but with lower yields (30-50%). In contrast to these two complexes, 1 and 2 fail to catalyze the aziridination of olefins in the presence of both the nitrene sources. All these observations have been rationalized based on the Cu(II)/Cu(I) redox potentials of the catalysts.     

Electronic effects on the interactions of complexes [Ru(phen)2(p-L)] (L=MOPIP, HPIP, and NPIP) with DNA

In order to explore the electronic effects of Ru(II) complexes binding to DNA, a series of Ru(II) complexes [Ru(phen)₂ (p-MOPIP)]²⁺ (1), [Ru(phen)₂ (p-HPIP)]²⁺ (2), and [Ru(phen)₂(p-NPIP)]²⁺ (3) were synthesized and characterized by elementary, ¹H NMR, and ES-MS analysis. The binding properties of these complexes to CT-DNA were investigated with spectroscopic methods and viscosity experiments. Furthermore, the computations for these complexes applying the density functional theory (DFT) method have also been performed. The results show that all of these complexes can well bind to DNA in intercalation mode and DNA-binding affinity of these complexes is greatly influenced by electronic effects of intercalating ligands. The intrinsic binding constants for 1, 2, and 3 are 0.20, 0.69, and 1.56 × 10⁵ M⁻¹, respectively. This order is in accordance with that of the electron-withdrawing ability of substituent [-OR < -OH < -NO₂]. Such a trend in electronic effects of Ru(II) complexes binding to DNA can be reasonably explained by the DFT calculations.     

Synthesis and structures of morpholine substituted new vic-dioxime ligand and its Ni(II) complexes

N,N^′-bis[4-(2-aminoethyl)morpholino]glyoxime (H₂L) (Fig. 1), has been prepared in various yields using three different methods. The most efficient of these methods is the technique of microwave irradiation. The crystal structures of H₂L, and of two nickel(II) complexes 1 and 2 have been determined by single crystal X-ray diffraction. Both nickel(II) complexes have a metal-ligand ratio of 1:2 in which the ligand coordinates through the two nitrogen atoms as do most vic-dioximes. The nickel(II) complexes are either hydrogen (1) or boron diphenyl bridged (2). Complex 1 was synthesized by reacting H₂L with nickel(II) chloride in refluxing ethanol. Complex 2 was prepared at room temperature in an ethanol solution containing excess NaBPh₄. Elemental analyses, NMR(¹H, ¹³C), IR and mass data are also presented.