N(4)-Tolyl-2-acetylpyridine thiosemicarbazones and their platinum(II,IV) and gold(III) complexes: cytotoxicity against human glioma cells and studies on the mode of action

Complexes [Au(2Ac4oT)Cl][AuCl₂] (1), [Au(H_py2Ac4mT)Cl₂]Cl·H₂O (2), [Au(H_py2Ac4pT)Cl₂]Cl (3), [Pt(H2Ac4oT)Cl]Cl (4), [Pt(2Ac4mT)Cl]·H₂O (5), [Pt(2Ac4pT)Cl] (6) and [Pt(L)Cl₂OH], L = 2Ac4mT (7), 2Ac4oT (8), 2Ac4pT (9) were prepared with N(4)-ortho- (H2Ac4oT), N(4)-meta- (H2Ac4mT) and N(4)-para- (H2Ac4pT) tolyl-2-acetylpyridine thiosemicarbazone. The cytotoxic activities of all compounds were assayed against U-87 and T-98 human malignant glioma cell lines. Upon coordination cytotoxicity improved in 2, 5 and 8. In general, the gold(III) complexes were more cytotoxic than those with platinum(II,IV). Several of these compounds proved to be more active than cisplatin and auranofin used as controls. The gold(III) complexes probably act by inhibiting the activity of thioredoxin reductase enzyme whereas the mode of action of the platinum(II,IV) complexes involves binding to DNA. Cells treated with the studied compounds presented morphological changes such as cell shrinkage and blebs formation, which indicate cell death by apoptosis induction.     

N,N′-bis(2-hydroxy-3-methoxybenzylidene)-1,3-diaminopropane dimeric 4f and 3d-4f heterodinuclear complexes: Syntheses, crystal structures and magnetic properties

Three novel N,N′-bis(2-hydroxy-3-methoxybenzylidene)-1,3-diaminopropane dimeric lanthanide complexes, namely, [{H₂L}Sm(NO₃)₃]₂·H₂O (1), [{H₂L}Gd(NO₃)₃]₄·CH₃OH (2), [{H₂L}Lu(NO₃)₃]₄·H₂O (3) (H₂L = N,N′-bis(2-hydroxy-3-methoxybenzylidene)-1,3-diaminopropane) and three new N,N′-bis(2-hydroxy-3-methoxybenzylidene)-1,3-diaminopropane 3d-Gd heterodinuclear complexes, namely, [{LCo}(CH₃COO)(CH₃COOH)Gd(NO₃)₂] (4), [{LNi(MeOH)₂}Gd(NO₃)₃]·2MeOH (5) and [{(L)Zn(HNO₃)}Gd(NO₃)₃]·NO₃·H₃O·MeOH (6) have been synthesized and isolated. X-ray crystallographical analysis reveals that complexes 1-3 are isomorphic with unique dimeric topology. Complexes 4-6 are of discrete 3d-4f dinuclear cores. Magnetic properties of complexes 2 and 4-6 are systematically investigated. Complexes 4 and 5 are ferromagnetic, while 2 and 6 are antiferromagnetic.     

Syntheses and structures of cobalt(III) alcoholate complexes formed by addition of a water molecule across 2-pyridyl substituted imine function

Schiff bases L1-L5 {N-[1-pyridine-2-ylethylidene]pyridine-2-amine (L1), 3-methyl-N-[1-pyridine-2-ylmethylidene]pyridine-2-amine (L2), 3-methyl-N-[1-pyridine-2-ylethylidene]pyridine-2-amine (L3), 4-methyl-N-[1-pyridine-2-ylmethylidene]pyridine-2-amine (L4), 4-methyl-N-[1-pyridine-2-ylethylidene]pyridine-2-amine (L5)} were synthesized and on reaction with Co(NO₃)₂·6H₂O, complexes having the molecular formulae [Co(L1O)₂]NO₃ (1), [Co(L2O)₂]NO₃·xH₂O (2a, x = 2; 2b, x = 3), [Co(L3O)₂]NO₃ (3), [Co(L4O)₂]NO₃·4H₂O (4), [Co(L5O)₂]NO₃ (5) were isolated from the respective imines. The salt [Co(L2O)₂]PF₆ (2c) was obtained by treating 2 with KPF₆. Complexes 1-5 were formed as a result of addition of a water molecule across the imine function and the resultant alcohol binds in its deprotonated form. The alcoholate ion remained bound in a facial tridentate fashion to the low-spin cobalt(III). X-ray crystal structure determination confirmed the presence of trans-trans-trans-N_AN_PO (A = aminopyridyl and P = pyridyl) disposition in 2a and cis-cis-trans-N_AN_PO in 2b, 2c and 4. Water dimers in 2a, 2b, 4 and water-nitrate ion network in 2a were other notable features.     

Gold(I) complexes with thiosemicarbazones: cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity

Complexes [Au(H2Ac4DH)Cl]?MeOH (1) [Au(H₂2Ac4Me)Cl]Cl (2) [Au(H₂2Ac4Ph)Cl]Cl?2H₂O (3) and [Au(H₂2Bz4Ph)Cl]Cl (4) were obtained with 2-acetylpyridine thiosemicarbazone (H2Ac4DH), its N(4)-methyl (H2Ac4Me) and N(4)-phenyl (H2Ac4Ph) derivatives, as well as with N(4)-phenyl 2-benzoylpyridine thiosemicarbazone (H2Bz4Ph). The compounds were cytotoxic to Jurkat (immortalized line of T lymphocyte), HL-60 (acute myeloid leukemia), MCF-7 (human breast adenocarcinoma) and HCT-116 (colorectal carcinoma) tumor cell lines. Jurkat and HL-60 cells were more sensitive than MCF-7 and HCT-116 cells. Upon coordinating to the gold(I) metal centers in complexes (2) and (4), the cytotoxic activity of the H2Ac4Me and H2Bz4Ph ligands increased against the HL-60 and Jurkat tumor cell lines. 2 was more active than auranofin against both leukemia cells. Most of the studied compounds were less toxic than auranofin to peripheral blood mononuclear cells (PBMC). All compounds induced DNA fragmentation in HL-60 and Jurkat cells indicating their pro-apoptotic potential. Complex (2) strongly inhibited the activity of thioredoxin reductase (TrxR), which suggests inhibition of TrxR to be part of its mechanism of action.     

Syntheses and structures of heterobimetallic complexes derived from [Ga(edt)2] as a metalloligand (edt = SC2H4S): Potential precursors for ternary materials MGaS2 (M = Cu or Ag)

Metathesis reaction between equimolar amount of [Et₄N][GaCl₄] and Na₂edt in methanol resulted in the formation of the dichloro complex [Et₄N][Ga(edt)Cl₂] (1), whereas reaction of [Et₄N][GaCl₄] with two equivalents of Na₂edt in methanol gave the complex [Et₄N][Ga(edt)₂] (2) which can act as a metalloligand. Treatment of 2 with M(PPh₃)₂NO₃ in DMF/CH₂Cl₂ afforded the heterobimetallic complexes [Ga(edt)₂M-(PPh₃)₂] (M = Cu 3, Ag 4) in moderate yields. The structures of 1-4 were determined by single-crystal X-ray diffraction analyses. Both [Ga(edt)Cl₂]⁻ and [Ga(edt)₂]⁻ anions have a distorted tetrahedral geometry. The former consists of one five-membered ring formed by chelating dithiolate and two terminal chloride atoms while the latter consists of two five-membered rings formed by two the chelating dithiolates. Complexes 3 and 4 consist of metalloligand [Ga(edt)₂]⁻ anion chelated to [M(PPh₃)₂]⁺via the sulfur atoms. Both tetrahedrally coordinated Ga and Cu(Ag) atoms are bridged by two sulfur atoms, forming a planar “GaS₂M” (M = Cu, Ag) core. Thermogravimetry analysis revealed that heterobimetallic complexes 3 and 4 decomposed to give the corresponding ternary metal sulfide materials.     

Modeling the effect of H-bonding interactions and molecular packing on the molecular structure of [Ag(ethylnicotinate)2]NO3 complex

The gas phase molecular structure of a single isolated molecule of [Ag(Etnic)₂NO₃];1 where Etnic = Ethylnicotinate was calculated using B3LYP method. The H-bonding interaction between 1 with one (complex 2) and two (complex 3) water molecules together with the dimeric formula [Ag(Etnic)₂NO₃]₂;4 and the tetrameric formula [Ag(Etnic)₂NO₃]₄;5 were calculated using the same level of theory to model the effect of intermolecular interactions and molecular packing on the molecular structure of the titled complex. The H-bond dissociation energies of complexes 2 and 3 were calculated to be in the range of 12.220–14.253 and 30.106–31.055 kcal?mol^?1, respectively, indicating the formation of relatively strong H-bonds between 1 and water molecules. The calculations predict bidentate nitrate ligand in the case of 1 and 2, leading to distorted tetrahedral geometry around the silver ion with longer Ag–O distances in case of 2 compared to 1, while 3 has a unidentate nitrate ligand leading to a distorted trigonal planar geometry. The packing of two [Ag(Etnic)₂NO₃] complex units; 4 does not affect the molecular geometry around Ag(I) ion compared to 1. In the case of 5, the two asymmetric units of the formula [Ag(Etnic)₂NO₃] differ in the bonding mode of the nitrate group, where the geometry around the silver ion is distorted tetrahedral in one unit and trigonal planar in the other. The calculations predicted almost no change in the charge densities at the different atomic sites except at the sites involved in the C–H?O interactions as well as at the coordinated nitrogen of the pyridine ring.

Synthesis, structure, and catalytic activity of chiral Cu(II) and Ag(I) complexes with (S,S)-1,2-diaminocyclohexane-based N4-donor ligands

Condensation of (S,S)-1,2-cyclohexanediamine with 2 equiv. of 2-pyridine carboxaldehyde in toluene in the presence of molecular sieves at 70 °C gives N,N′-bis(pyridin-2-ylmethylene)-(S,S)-1,2-cyclohexanediamine (S,S-1) in 95% yield. Reduction of 1 with an excess of NaBH₄ in MeOH at 50 °C gives N,N′-bis(pyridin-2-ylmethyl)-(S,S)-1,2-cyclohexanediamine (S,S-2) in 90% yield. Reaction of 1 or 2 with 1 equiv. of CuCl₂ · 2H₂O in methanol gives complexes [N-(pyridin-2-ylmethylene)-(S,S)-1,2-cyclohexanediamine]CuCl₂ (3) and [Cu(S,S-2)(H₂O)]Cl₂ · H₂O (4), respectively, in good yields. Complex 4 can further react with 1 equiv. of CuCl₂ · 2H₂O in methanol to give [Cu(S,S-2)][CuCl₄] (5) in 75% yield. The rigidity of the ligand coupled with the steric effect of the free anion plays an important role in the formation of the helicates. Treatment of ligand S,S-1 with AgNO₃ induces a polymer helicate {[Ag(S,S-1)][NO₃]}_n (6), while reaction of ligand 2 with AgPF₆ or AgNO₃ in methanol affords a mononuclear single helicate [Ag(S,S-2)][PF₆] (7) or a dinuclear double helicate [Ag₂(S,S-2)₂][NO₃]₂ · 2CH₃OH (8) in good yields, respectively. All compounds have been characterized by various spectroscopic data and elemental analyses. Compounds 1, 3-5, 7 and 8 have been further subjected to single-crystal X-ray diffraction analyses. The Cu(II) complexes do not show catalytic activity for allylation reaction, in contrast to Ag(I) complexes, but they do show catalytic activity for Henry reaction (nitroaldol reaction) that Ag(I) complexes do not.     

Metal–drug synergy: new ruthenium(II) complexes of ketoconazole are highly active against Leishmania major and Trypanosoma cruzi and nontoxic to human or murine normal cells

In our ongoing search for new metal-based chemotherapeutic agents against leishmaniasis and Chagas disease, six new ruthenium–ketoconazole (KTZ) complexes have been synthesized and characterized, including two octahedral coordination complexes—cis,fac-[Ru^IICl₂(DMSO)₃(KTZ)] (1) and cis-[Ru^IICl₂(bipy)(DMSO)(KTZ)] (2) (where DMSO is dimethyl sulfoxide and bipy is 2,2′-bipyridine)—and four organometallic compounds—[Ru^II(η⁶-p-cymene)Cl₂(KTZ)] (3), [Ru^II(η⁶-p-cymene)(en)(KTZ)][BF₄]₂ (4), [Ru^II(η⁶-p-cymene)(bipy)(KTZ)][BF₄]₂ (5), and [Ru^II(η⁶-p-cymene)(acac)(KTZ)][BF₄] (6) (where en is ethylenediamine and acac is acetylacetonate); the crystal structure of 3 is described. The central hypothesis of our work is that combining a bioactive compound such as KTZ and a metal in a single molecule results in a synergy that can translate into improved activity and/or selectivity against parasites. In agreement with this hypothesis, complexation of KTZ with Ru^II in compounds 3–5 produces a marked enhancement of the activity toward promastigotes and intracellular amastigotes of Leishmania major, when compared with uncomplexed KTZ, or with similar ruthenium compounds not containing KTZ. Importantly, the selective toxicity of compounds 3–5 toward the leishmania parasites, in relation to human fibroblasts and osteoblasts or murine macrophages, is also superior to the selective toxicities of the individual constituents of the drug. When tested against Trypanosoma cruzi epimastigotes, some of the organometallic complexes displayed activity and selectivity comparable to those of free KTZ. A dual-target mechanism is suggested to account for the antiparasitic properties of these complexes.     

Synthesis, structures and luminescent properties of new heterobimetallic Zn-4f Schiff base complexes

A series of new 3d-4f heterobimetallic Schiff base complexes of the general formula [Zn(μ-L²)Ln(NO₃)₃(H₂O)_n] (Ln = La 1, Nd 2, Gd 3, Er 4 and Yb 5; n = 1 or 2; H₂L² = N,N′-bis(3-methoxy-5-p-tolylsalicylidene)ethylene-1,2-diamine) are synthesized and characterized. Complexes 1, 2, 4 and 5 are structurally characterized by X-ray crystallography. The photophysical properties of these complexes are also investigated. At room temperature, complexes 1-5 exhibit similar solution absorption and emission spectra in the UV-Vis region. Furthermore, compounds 2, 4 and 5 exhibit solution emission corresponding to the lanthanide(III) ion in the near-infrared region at room temperature. The triplet state emission of the 3d-4f bimetallic complexes without energy transfer is also determined through the photophysical study of complex 3.     

Vanadium complexes with 2-pyridineformamide thiosemicarbazones: In vitro studies of insulin-like activity

Reaction of VOCl₂ with 2-pyridineformamide thiosemicarbazone (H2Am4DH) and its N(4)-methyl (H2Am4Me), N(4)-ethyl (H2Am4Et) and N(4)-phenyl (H2Am4Ph) derivatives in ethanol gave as products [VO(H2Am4DH)Cl₂] (1), [VO(H2Am4Me)Cl₂] · 1/2HCl (2), [VO(H2Am4Et)Cl₂] · HCl (3) and [VO(2Am4Ph)Cl] (4). Upon the dissolution of 1-4 in water, oxidation immediately occurs with the formation of [VO₂(2Am4DH)] (5), [VO₂(2Am4Me)] (6), [VO₂(2Am4Et)] (7) and [VO₂(2Am4Ph)] (8). The crystal and molecular structures of 5 and 6 were determined. Complexes 5-8 inhibited glycerol release in a similar way to that observed with insulin but showed a low enhancing effect on glucose uptake by rat adipocytes.     

Hexachlororhenate(IV) salts of organic radical cations

The ionic salts (p-rad)₂[ReCl₆] (1) and (m-rad)₂[ReCl₆] (2) (p/m-rad = 2-(4/3-N-methylpyridinium)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl-3-N-oxide) have been prepared and their crystal structures determined by single-crystal X-ray diffraction. The nitronyl nitroxide cations in compound 1 show a layered disposition, whereas the [ReCl₆]²⁻ units are placed between these layers. The nitronyl nitroxide cations in compound 2 adopt an hexagonal array but they do not result in layers. Bulk magnetic properties of 1 and 2 have been investigated in the temperature range 2-300 K. Both compounds show weak but significant intermolecular antiferromagnetic interactions.     

N,N′-Bis(3-methoxysalicylidene)propane-1,2-diamine mononuclear 4f and heterodinuclear Cu-4f complexes: Synthesis, crystal structure and electrochemical properties

Reactions of H₂L [H₂L = N,N′-bis(3-methoxysalicylidene)propane-1,2-diamine] and Ln(NO₃)₃ · 6H₂O give rise to two different mononuclear 4f complexes, namely, {[(H₂L)La(NO₃)₃(MeOH)] · H₂O}_n (1) and [(H₂L)Nd(NO₃)₃] (2). Further additions of Cu(Ac)₂ · H₂O to the mononuclear 4f complexes yield expected heterodinuclear Cu-4f complexes [LCu(Me₂CO)Ln(NO₃)₃] (3, Ln = Nd; 4, Ln = Eu; 5, Ln = Dy). Complex 1 is a unique 1D polymeric chain structure, and 2 is one of the few structurally characterized discrete hexadentate salen-type mononuclear 4f complexes. Complexes 3-5 are similar to their analogues. However, they are prepared by a reversed synthetic route in contrast to their isomorphic complexes. Electrochemical behavior of heterodinuclear Cu-4f complexes 3-5 has been examined by cyclic voltammetry in acetonitrile. The redox potential of heterodinuclear Cu-4f complexes 3-5 shows significant anodic shift comparing to that of mononuclear copper complex (LCu). A tendency of anodic shift was observed in a sequence of 3 < 4 < 5. This results from the modulating effect of coordination geometry around Cu(II) ion on redox potential.     

Arene-Ru(II)-chloroquine complexes interact with DNA, induce apoptosis on human lymphoid cell lines and display low toxicity to normal mammalian cells

The complexes [Ru(η⁶-p-cymene)(CQ)Cl₂] (1), [Ru(η⁶-benzene)(CQ)Cl₂] (2), [Ru(η⁶-p-cymene)(CQ)(H₂O)₂][BF₄]₂ (3), [Ru(η⁶-p-cymene)(en)(CQ)][PF₆]₂ (4), [Ru(η⁶-p-cymene)(η⁶-CQDP)][BF₄]₂ (5) (CQ = chloroquine base; CQDP = chloroquine diphosphate; en = ethylenediamine) interact with DNA to a comparable extent to that of CQ and in analogous intercalative manner with no evidence for any direct contribution of the metal, as shown by spectrophotometric and fluorimetric titrations, thermal denaturation measurements, circular dichroism spectroscopy and electrophoresis mobility shift assays. Complexes 1-5 induced cytotoxicity in Jurkat and SUP-T1 cancer cells primarily via apoptosis. Despite the similarities in the DNA binding behavior of complexes 1-5 with those of CQ the antitumor properties of the metal drugs do not correlate with those of CQ, indicating that DNA is not the principal target in the mechanism of cytotoxicity of these compounds. Importantly, the Ru-CQ complexes are generally less toxic toward normal mouse splenocytes and human foreskin fibroblast cells than the standard antimalarial drug CQDP and therefore this type of compound shows promise for drug development.     

Synthesis and structures of zinc complexes with new binucleating ligands containing alkoxide bridges, and their activities in the hydrolysis of tris(p-nitrophenyl)phosphate

Four new binucleating ligands featuring a hydroxytrimethylene linker between two coordination sites (1,3-bis{N-[3-(dimethylamino)propyl]-N-methylamino}propan-2-ol, HL¹; 1,3-bis{N-[2-(dimethylamino)ethyl]-N-methylamino}propan-2-ol, HL²; 1,3-bis[bis(2-methoxyethyl)amino]propan-2-ol, HL³; and 1-bis[(2-methoxyethyl)amino]-3-{N-[2-(dimethylamino)ethyl]-N-methylamino}propan-2-ol, HL⁴) were synthesized, along with the corresponding zinc complexes. The structures of three dinuclear zinc complexes ([Zn₂L¹(μ-CH₃COO)₂]BPh₄ (1), [Zn₂L³(μ-CH₃COO)₂]BPh₄ (3), and [Zn₂L⁴(μ-CH₃COO)(CH₃COO)(EtOH)]BPh₄ (4)) and a tetranuclear zinc complex ({[Zn₂L²(μ-CH₃COO)]₂(μ-OH)₂}(BPh₄)₂ (2)) were revealed by X-ray crystallography. Hydrolysis of tris(p-nitrophenyl)phosphate (TNP) by these zinc complexes in an acetonitrile solution containing 5% Tris buffer (pH 8.0) at 30 °C was investigated spectrophotometrically and by ³¹P NMR. Although zinc complexes 1, 3, and 4 did not show hydrolysis activity, the tetranuclear zinc complex 2, containing μ-hydroxo bridges, was capable of hydrolyzing TNP. This suggests that the hydroxide moiety in the complex may have an important role in the hydrolysis reaction.     

Synthesis and structural characterization of dinuclear complexes of trivalent aluminum, gallium, indium and chromium derived from pyrazole-2-ethanol

The reaction of 1-(2-hydroxyethyl)-3,5-dimethylpyrazole (HL) with anhydrous metal(III) halides (M = Al, Ga, In and Cr) results in the isolation of four novel dinuclear complexes [Al(μ-L)Cl₂]₂ (1), [Ga(μ-L)Cl₂]₂ (2), [In(μ-L)Br₂(H₂O)]₂·2thf (3) and [Cr(μ-L)Cl₂(H₂O)]₂·1.5thf (4) in good yields. The new complexes have been characterized with the aid of analytical and spectroscopic studies. A single crystal X-ray structure determination in each case confirms the dimeric structure for all the complexes in the solid-state. The pyrazole ethanol ligand binds to the metal through both pyrazole nitrogen and bridging alkoxide oxygen terminals with the formation of a central M₂O₂ core involving the ethoxide anion. The metal(III) center is pentacoordinated in compounds 1 and 2, while it is hexacoordinated in compounds 3 and 4.     

Interactions of arene-Ru(II)-chloroquine complexes of known antimalarial and antitumor activity with human serum albumin (HSA) and transferrin

The interactions of π-arene-Ru(II)-chloroquine complexes with human serum albumin (HSA), apotransferrin and holotransferrin have been studied by circular dichroism (CD) and UV-Visible spectroscopies, together with isothermal titration calorimetry (ITC). The data for [Ru(η⁶-p-cymene)(CQ)(H₂O)Cl]PF₆ (1), [Ru(η⁶-benzene)(CQ)(H₂O)Cl]PF₆ (2), [Ru(η⁶-p-cymene)(CQ)(H₂O)₂][PF₆]₂ (3), [Ru(η⁶-p-cymene)(CQ)(en)][PF₆]₂ (4), [Ru(η⁶-p-cymene)(η⁶-CQDP)][BF₄]₂ (5) (CQ: chloroquine; DP: diphosphate; en: ethylenediamine), in comparison with CQDP and [Ru(η⁶-p-cymene)(en)Cl][PF₆] (6) as controls demonstrate that 1, 2, 3, and 5, which contain exchangeable ligands, bind to HSA and to apotransferrin in a covalent manner. The interaction did not affect the α-helical content in apotransferrin but resulted in a loss of this type of structure in HSA. The binding was reversed in both cases by a decrease in pH and in the case of the Ru-HSA adducts, also by addition of chelating agents. A weaker interaction between complexes 4 and 6 and HSA was measured by ITC but was not detectable spectroscopically. No interactions were observed for complexes 4 and 6 with apotransferrin or for CQDP with either protein. The combined results suggest that the arene-Ru(II)-chloroquine complexes, known to be active against resistant malaria and several lines of cancer cells, also display a good transport behavior that makes them good candidates for drug development.     

New diacylglyceryltrimethylhomoserines from the marine microalga Nannochloropsis granulata and their nitric oxide inhibitory activity

Chemical investigation of polar lipids from the marine eustigmatophyte microalga Nannochloropsis granulata led to the isolation of six betaine lipid diacylglyceryltrimethylhomoserine (DGTS), namely, (2S)-1,2-bis-O-eicosapentaenoylglyceryl-3-O-4′-(N,N,N-trimethyl)-homoserine (1), (2S)-1-O-eicosapentaenoyl-2-O-arachidonoylglyceryl-3-O-4′-(N,N,N-trimethyl)-homoserine (2), (2S)-1-O-eicosapentaenoyl-2-O-myristoylglyceryl-3-O-4′-(N,N,N-trimethyl)-homoserine (3), (2S)-1-O-eicosapentaenoyl-2-O-palmitoylglyceryl-3-O-4′-(N,N,N-trimethyl)-homoserine (4), (2S)-1-O-eicosapentaenoyl-2-O-palmitoleoylglyceryl-3-O-4′-(N,N,N-trimethyl)-homoserine (5), and (2S)-1-O-eicosapentaenoyl-2-O-linoleoylglyceryl-3-O-4′-(N,N,N-trimethyl)-homoserine (6). Structures of the isolated DGTSs were elucidated based on both spectroscopic technique and degradation methods. This is the first report of isolation of 1 in pure state, and 2–6 are all new compounds. The isolated betaine lipids showed dose-dependent nitric oxide (NO) inhibitory activity against lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells. Further study suggested that these betaine lipids (1–6) inhibit NO production in RAW264.7 macrophage cells through downregulation of inducible nitric oxide synthase expression, indicating the possible use as an anti-inflammatory agent. This is the first report of DGTS with anti-inflammatory activity.     

Reactivity study of arene(azido)ruthenium N∩O-base complexes with activated alkynes

Substitution reaction of chloro η⁶-arene ruthenium N∩O-base complexes [(η⁶-arene)Ru(N∩O)Cl] [N∩O = pyrazine-2-carboxylic acid (pca-H), 8-hydroxyquinoline (hq-H); arene = p-ⁱPrC₆H₄Me, N∩O = hq (1); arene = C₆Me₆, N∩O = hq (2)] with NaN₃ yield the neutral arene ruthenium azido complexes of the general formula [(η⁶-arene)Ru(N∩O)N₃] [N∩O = pca, arene = p-ⁱPrC₆H₄Me (3), arene = C₆Me₆ (4); N∩O = hq, arene = p-ⁱPrC₆H₄Me (5), arene = C₆Me₆ (6)]. These complexes undergo [3 + 2] dipolar cycloaddition reaction with activated alkynes dimethyl and diethyl acetylenedicarboxylates to yield the arene triazole complexes [(η⁶-arene)Ru(N∩O){N₃C₂(CO₂R)₂}] [N∩O = pca, R = Me, arene = p-ⁱPrC₆H₄Me (7), C₆Me₆ (8); R = Et, arene = p-ⁱPrC₆H₄Me (9), C₆Me₆ (10); N∩O = hq, R = Me, arene = p-ⁱPrC₆H₄Me (11) C₆Me₆ (12); R = Et, arene = p-ⁱPrC₆H₄Me (13), C₆Me₆ (14)]. On the bases of proton NMR study, in the above triazole complexes N(2) isomers are assigned with dimethylacetylenedicarboxylate whereas N(1) isomers with diethylacetylenedicarboxylate. All complexes have been characterized by IR and NMR spectroscopy as well as by elemental analysis. The molecular structures of the azido complexes [(η⁶-p-ⁱPrC₆H₄Me)Ru(pca)N₃] (3), [(η⁶-p-ⁱPrC₆H₄Me)Ru(hq)N₃] (5) and [(η⁶-C₆Me₆)Ru(hq)N₃] (6) have been established by single crystal X-ray diffraction studies.     

One-dimensional silver(I) and mercury(II) complexes with 1,4-bis(1-benzyl-benzimidazol-2-yl)cyclohexane (N-BBzBimCH)

The crystal structures of four Ag(I) and Hg(II) complexes of the ligand 1,4-bis(1-benzyl-benzimidazol-2-yl)cyclohexane (N-BBzBimCH) have been described, that is, [Hg₂(N-BBzBimCH)Cl₄] (1), [Hg(N-BBzBimCH)Br₂] (2), [Ag(N-BBzBimCH)](NO₃)(H₂O) (3) and [Ag₂(N-BBzBimCH)(CF₃OCO)₂] (4). All these compounds show 1D polymeric structures in the solid state. In complexes 1 and 4, the chloride ions and the trifluoroacetate groups bridge the [Hg₂(N-BBzBimCH)Cl₂] and [Ag₂(N-BBzBimCH)] fragments, respectively, to generate 1D polymers. While the bromide ions in complex 2 and nitrate groups in complex 3 are only serving as terminal ligands to suffice the coordination geometry of the metal centers. In all cases, weak intermolecular interactions such as C-H?X (X = Cl, Br) contacts, hydrogen bonds, π-π interactions and C-H?π stacking play important roles to extend the 1D chain structures to 2D network. Solid state fluorescence of these compounds was also studied.     

Bismuth(III) complexes with 2-acetylpyridine- and 2-benzoylpyridine-derived hydrazones: Antimicrobial and cytotoxic activities and effects on the clonogenic survival of human solid tumor cells

Complexes [Bi(2AcPh)Cl₂]·0.5H₂O (1), [Bi(2AcpClPh)Cl₂] (2), [Bi(2AcpNO₂Ph)Cl₂] (3), [Bi(2AcpOHPh)Cl₂]·2H₂O (4), [Bi(H2BzPh)Cl₃]·2H₂O (5), [Bi(H2BzpClPh)Cl₃] (6), [Bi(2BzpNO₂Ph)Cl₂]·2H₂O (7) and [Bi(H2BzpOHPh)Cl₃]·2H₂O (8) were obtained with 2-acetylpyridine phenylhydrazone (H2AcPh), its -para-chloro-phenyl- (H2AcpClPh), -para-nitro-phenyl (H2AcpNO₂Ph) and -para-hydroxy-phenyl (H2AcpOHPh) derivatives, as well as with the 2-benzoylpyridine phenylhydrazone analogues (H2BzPh, H2BzpClPh, H2BzpNO₂Ph, H2BzpOHPh).Upon coordination to bismuth(III) antibacterial activity against Gram-positive and Gram-negative bacterial strains significantly improved except for complex (4).The cytotoxic effects of the compounds under study were evaluated on HL-60, Jurkat and THP-1 leukemia, and on MCF-7 and HCT-116 solid tumor cells, as well as on non-malignant Vero cells. In general, 2-acetylpyridine-derived hydrazones proved to be more potent and more selective as cytotoxic agents than the corresponding 2-benzoylpyridine-derived counterparts.Exposure of HCT-116 cells to H2AcpClPh, H2AcpNO₂Ph and complex (3) led to 99% decrease of the clonogenic survival. The IC₅₀ values of these compounds were three-fold smaller when cells were cultured in soft-agar (3D) than when cells were cultured in monolayer (2D), suggesting that they constitute interesting scaffolds, which should be considered in further studies aiming to develop new drug candidates for the treatment of colon cancer.