Synthesis and crystal structure of a cobalt(II) coordination polymer constructed from 2,6-pyridinedicarboxylate anion and 1,3-bis(4-pyridyl)propane nitrogen ligand

The coordination polymer named {[Co(H₂O)₄(BPP)][Co(dipic)₂]·H₂O}_n (dipic = 2,6-pyridinedicarboxylate and BPP = 1,3-bis(4-pyridyl)propane) has been synthesized by the diffusion method and characterized by thermal analysis, vibrational spectroscopy and single crystal X-ray diffraction analysis. The compound is formed by an one-dimensional polymeric cationic chain, in which the BPP ligands connect the Co2 sites, and an anionic moiety formed by Co1 center and two dipic²⁻ anions. Both crystallographic independent metal sites adopt a distorted octahedral geometry. Co2 center is coordinated by two nitrogen atoms from BPP ligands and four oxygen atoms from aqua ligands, while Co1 center is coordinated by two nitrogen atoms and four oxygen atoms from two dipic²⁻ anions. The cationic and anionic moieties are connected through hydrogen bonding interactions leading to a 3D supramolecular array.     

Four mixed-ligands lead(II) complexes based on 8-hydroxyquinolin (8-HQuin), [Pb(8-Quin)X]; X = 4-pyridinecarboxylate, acetate, thiocyanate and nitrate; structural and thermal studies

Lead(II) 8-hydroxychinolate complexes (8-Quin) containing four different anions, [Pb(8-Quin)X]; X = 4-pyridinecarboxylate (1), acetate (2), thiocyanate (3) and nitrate (4), have been synthesized and characterized by elemental analysis, IR-, ¹H NMR- and ¹³C NMR-spectroscopy. All these compounds were structurally characterized by single-crystal X-ray diffraction. The thermal stabilities of compounds 1–4 were studied by thermal gravimetric (TG) and differential thermal analyses (DTA). The results show the influence of different counter-ions to form dimers in compound 2, one-dimensional polymer in compound 4 and two-dimensional polymer in compounds 1 and 3.     

Affinity labeling of catechol-O-methyltransferase with N-iodoacetyl-3,5-dimethoxy-4-hydroxyphenylethylamine

Catechol-O-methyltransferase is inactivated rapidly by incubation with N-iodoacetyl-3,5-dimethoxy-4-hydroxyphenylethylamine; not by the N-acetyl analogue. Iodoacetate or iodoacetamide produce slight inactivation. Inactivation is first order with respect to enzyme activity. A kinetic analysis suggests the formation of a dissociable enzyme-inhibitor complex prior to inactivation. Substrate, 3,4-dihydroxybenzoate, protects the enzyme from alkylation and loss of activity.     

Mercury complexes with the ligand benzaldehyde-N(4),N(4)-dimethylthiosemicarbazone

The Schiff base benzaldehyde-N(4),N(4)-dimethylthiosemicarbazone (LH) and its complexes [Hg(NO₃)(LH)₂]NO₃ (1), [Hg(L)₂] (2), [Hg(LH)₂(μ-X)₂HgX₂] [X = Cl (3), Br (4)], [HgI(LH)(μ-I)₂HgI(LH)] (5) and [HgI₂(LH)] (6) have been synthesized and characterized by IR, mass spectrometry, ¹H and ¹³C NMR and by single crystal X-ray diffraction. All the complexes were obtained in ethanol and complex 2, in which the ligand is deprotonated, in addition needs the presence of basic medium. From mercury(II) iodide two complexes with the same molar ratio but with different structures were isolated. In all the complexes the ligand acts as a NS chelate, except in complex 5 in which is only S-donor. The coordination number of the mercury ion and the structures of the complexes depend on the counterion. Complexes 1, 2 and 6 are monomeric species but with different coordination spheres: N₂S₂O₂ with a distorted octahedral arrangement in complex 1, and N₂S₂ or NSI₂ in a pseudo-tetrahedral geometry in complexes 2 and 6, respectively. However, 3, 4 and 5 are binuclear complexes with two halido bridges, but they show two different structures. In 3 and 4, each mercury ion has a different environment giving an asymmetric structure, one is bonded to two NS-ligands and two halido bridges in a distorted octahedral geometry, and the other one has a tetrahedral environment formed by four halido ligands. In complex 5 both mercury ions are equivalent with a SI₃ distorted tetrahedral coordination sphere, formed by one S-bonded ligand, one terminal iodido and two iodido bridges.     

Enantioseparation of racemic 4-aryl-3,4-dihydro-2(1H)-pyrimidones on chiral stationary phases based on 3,5-dimethylanilides of N-(4-alkylamino-3,5-dinitro)benzoyl L-alpha-amino acids

Three novel chiral packing materials for high-performance liquid chromatography were prepared by covalently binding of (2S)-N-(3,5-dimethylphenyl)-2-[(4-chloro-3,5-dinitrophenyl)carbonylamino]propan-amide (7), (2S)-N-(3,5-dimethylphenyl)-2-[(4-chloro-3,5-dinitrophenyl)carbonylamino]-4-methylpentanamide (8), and (2S)-N-(3,5-dimethylphenyl)-2-[(4-chloro-3,5-dinitrophenyl)carbonyl-amino]-2-phenylacetamide (9) to aminopropyl silica. The resulting chiral stationary phases (CSPs 1-3) proved effective for the resolution of racemic 4-aryl-3,4-dihydro-2(1H)-pyrimidone derivatives (TR 1-14). The mechanism of their enantioselection, supported by the elution order of (S)-TR 13 and (R)-TR 13 and molecular modeling of the complex of the slower running (S)-TR 13 with CSP 1 is discussed.     

Trinuclear-based coordination compounds of Mn(II) and Co(II) with 4-amino-3,5-dimethyl-1,2,4-triazole and azide and thiocyanate anions: Synthesis, structure and magnetic properties

A 2D layer complex 1 and a linear trinuclear complex 2 with mixed ligands have been synthesized and characterized by elemental analyses, IR and single-crystal X-ray diffraction. In 1, the Mn(II) ions are six-coordinated and lie in distorted octahedron coordination environments. Complex 1 is connected into a 2D layer structure based on a linear trinuclear Mn₃(admtrz)₄(N₃)₆ (admtrz = 4-amino-3,5-dimethyl-1,2,4-triazole) building unit with either (6,3) topology when Mn1 cations as three-connected nodes or (4,4) network when the coordination trinuclear units being regarded as four connected nodes. In 2, the Co(II) ions are in slightly distorted octahedron coordination geometries. The magnetic behaviors are investigated in the temperature range 1.8-300 K. The magnetic susceptibility measurements show that the Mn(II) ions of complex 1 are weakly antiferromagnetically coupled with g = 1.98(1), J1 = −6.31(5) cm⁻¹ and J2 = −1.88(1) cm⁻¹. There is dominant zero field splitting (ZFS) effects with g values, g_// = 2.38(2) and g_⊥ = 4.96(4), indicated a significant presence of the spin-orbit coupling and magnetization experiment reveals large, uniaxial zero-field splitting parameters of D = −29.55 cm⁻¹ for 2.     

Synthesis and bioactivity of 3,5-dimethylpyrazole derivatives as potential PDE4 inhibitors

A series of 3,5-dimethylpyrazole derivatives containing 5-phenyl-2-furan moiety were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. Bioassay results showed that the title compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNFα release. Among the designed compounds, compound If showed the best inhibitory activity against PDE4B with the IC₅₀ value of 1.7?μM, which also showed good in vivo activity in animal models of asthma/COPD and sepsis induced by LPS. The primary structure–activity relationship (SAR) study and docking results suggested that introduction of the substituent groups to the phenyl ring at the para-position, especially methoxy group, was helpful to enhance inhibitory activity against PDE4B.     

Mechanics of root elongation and the effects of 3,5-diiodo-4-hydroxybenzoic acid (DIHB)

Summary This paper reports the results of two series of experiments. In the first the effects of DIHB on the rate of root elongation were compared on unstressed roots and on roots stressed by mechanical impedance and by inadequate levels of aeration. Barley plants were grown in beds of small glass spheres through which nutrient solution was circulated. Mechanical impedance of 25 kPa was applied by subjecting the beds to a confining pressure. Inadequate aeration was obtained by reducing the oxygen concentration in the nutrient solution to 5%. The second series examined possible effects of DIHB on the elastic modulus of root tips of wheat and pea. Elastic modulus gives an indication of the behaviour of roots in structured soil where penetration of peds can be limited by the buckling of root tips. The elastic modulus was measured in experiments of the static cantilever type on roots previously immersed in solutions of polyethylene glycol of different osmotic potential. Elastic modulus measurements can also detect any changes in turgor pressure and wilting characteristics of roots and can therefore help to identify the mechanisms of action of DIHB. DIHB caused increases in root elongation relative to controls in all cases: 26±5.7% in unstressed roots, 14±6.4% in mechanically impeded roots and 54±9.8% in roots growing in 5% oxygen. DIHB had no effect on the elastic modulus, osmotic or turgor pressure of the roots. It is concluded that DIHB acts by modifying the cell wall extensibility factor.     

3,5-Bis(benzylidene)-4-piperidones and related N-acyl analogs: A novel cluster of antimalarials targeting the liver stage of Plasmodium falciparum

Drug resistance is a major challenge in antimalarial chemotherapy. In addition, a complete cure of malaria requires intervention at various stages in the development of the parasite within the host. There are only a few antimalarials that target the liver stage of the Plasmodium species which is an essential part of the life cycle of the malarial parasite. We report a series of antimalarial 3,5-bis(benzylidene)-4-piperidones and related N-acyl analogs 1–5, a number of which exhibit potent in vitro growth-inhibiting properties towards drug-sensitive D6 and drug-resistant C235 strains of Plasmodium falciparum as well as inhibiting the liver stage development of the malarial life cycle. The compounds 2b (IC₅₀: 165 ng/mL), 3b (IC₅₀: 186 ng/mL), 5c (IC₅₀: 159 ng/mL) and 5d (IC₅₀: 93.5 ng/mL) emerged as lead molecules that inhibit liver stage Plasmodium berghei and are significantly more potent than chloroquine (IC₅₀: >2000 ng/mL) and mefloquine (IC₅₀: >2000 ng/mL) in this screen. All the compounds that showed potent inhibitory activity against the P. berghei liver stage were nontoxic to human HepG2 liver cells (IC₅₀: >2000 ng/mL). The compounds 5a and 5b exhibit comparable metabolic stability as chloroquine and mefloquine in human plasma and the most potent compound 5d demonstrated suitable permeability characteristics using the MDCK monolayer. These results emphasize the value of 3,5-bis(benzylidene)-4-piperidones as novel antimalarials for further drug development.     

A 3-D (3,5)-connected Cd coordination framework with unique twofold interpenetrating (4·6)(4·6·8) network topology

Assembly of N,N′-bis(4-picolinoyl)hydrazine (H₂L) with cadmium nitrate in the presence of dicyanamide anion (dca) affords a new coordination polymer {[Cd(HL)(dca)] · (H₂O)_0.5}_n (1), in which the [Cd(HL)]_n layers are extended by dca bridges to result in a three-dimensional (3-D) coordination framework. The network structure of 1 has unusual (3,5)-connectivity and represents a new type of (4·6²)(4·6⁶·8³) topology. Two such identical and complementary networks are entangled to generate a twofold parallel interpenetrating supramolecular lattice.     

Ortho-metallation of a phenyl ring with antimony(V)

Reaction of Ph₃SbCl₂ with LiNCPh₂ produces via ortho metallation of one of the phenyl groups of the imino functionality. This is the first reported example of ortho metallation of a phenyl ring by a pnictogen.     

Novel hybrid molecules of 3,5-bis(benzylidene)-4-piperidones and dichloroacetic acid which demonstrate potent tumour-selective cytotoxicity

A novel class of hybrid molecules 2a-o was designed as candidate antineoplastic agents from dichloroacetic acid which is a known inhibitor of pyruvate dehydrogenase kinase and a number of cytotoxic 3,5-bis(benzylidene)-4-piperidones 1. In general these new hybrid molecules are potent cytotoxins towards human HCT116 colon cancer cells. A number of lead molecules emerged having the IC₅₀ values in the double digit nanomolar range. Most of these compounds are less toxic to human CRL1790 non-malignant colon cells and hence the selectivity index (SI) figures for most of the compounds are huge; in the case of 2c-g, m, n, the SI values are in excess of 100. Compounds 2g, 2j, 2m and 2n displayed >100-fold higher potency than the reference drug 5-FU. Quantitative structure-activity relationships revealed that the potencies of the compounds in series 2 increase as the magnitude of the Hammett σ and Taft σ* values rise. X-ray crystallographic of a representative compound 2c revealed various structural features which may influence cytotoxic potencies. Several representative compounds lowered the mitochondrial membrane potential and increased the production of reactive oxygen species in HCT116 cells. A minimal effect was noted in altering the percentage of cells in different phases of the cell cycle. Some future directions have been outlined for analog development.     

Trifluoromethyl-substituted 3,5-bis(arylidene)-4-piperidones as potential anti-hepatoma and anti-inflammation agents by inhibiting NF-кB activation

Some methoxy-, hydroxyl-, pyridyl-, or fluoro-substituted 3,5-bis(arylidene)-4-piperidones (BAPs) could reduce inflammation and promote hepatoma cell apoptosis by inhibiting activation of NF-κB, especially after introduction of trifluoromethyl. Herein, a series of trifluoromethyl-substituted BAPs (4-30) were synthesised and the biological activities were evaluated. We successfully found the most potential 16, which contains three trifluoromethyl substituents and exhibits the best anti-tumour and anti-inflammatory activities. Preliminary mechanism research revealed that 16 could promote HepG2 cell apoptosis in a dose-dependent manner by down-regulating the expression of Bcl-2 and up-regulating the expression of Bax, C-caspase-3. Meanwhile, 16 inhibited activation of NF-κB by directly inhibiting the phosphorylation of p65 and IκBα induced by LPS, together with indirectly inhibiting MAPK pathway, thereby exhibiting both anti-hepatoma and anti-inflammatory activities. Molecular docking confirmed that 16 could bind to the active sites of Bcl-2, p65, and p38 reasonably. The above results suggested that 16 has enormous potential to be developed as a multifunctional agent for the clinical treatment of liver cancers and inflammatory diseases.     

3,5-Dicaffeoyl-4-malonylquinic acid reduced oxidative stress and inflammation in a experimental model of inflammatory bowel disease

Abstract

Aim: The aim of the present study was to examine the effects of 3,5-dicaffeoyl-4-malonylquinic acid (CA1), extract from Centella Asiatica, in rats subjected to experimental colitis.

Results: Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulphonic acid (DNBS). CA1 was administered daily orally (0.2 or 2 mg/kg). Four days after DNBS administration, treatment with CA1 significantly reduced the appearance of diarrhoea and the loss of body weight. This was associated with a significant reduction in colonic MPO activity. CA1 also reduced NF-κB activation, the pro-inflammatory cytokines release, the appearance of I-NOS, nitrotyrosine, PARP and proMMP-9 and -2 activity in the colon and reduced the up-regulation of ICAM-1 and the expression of P-Selectin.

Conclusions: The results of this study suggested that administration of CA1 may be beneficial for treatment of inflammatory bowel disease.     

Structural studies of decavanadate compounds with organic molecules and inorganic ions in their crystal packing

The formation of decavanadates containing amine counter-ions is explored to get a better insight into the resulting crystal packing. From mixtures containing the Schiff base H₂(SO₃-sal)₂en and vanadate, two different compounds containing decavanadate units have been characterised by X-ray diffraction. The structure of 1 consists of [V₁₀O₂₈]⁶⁻ monomers united by K⁺, ethylenediamine cations and H₂O molecules, which act as bridging atoms between the layers, forming a three-dimensional array. The structure of 2 contains vanadium triprotonated decavanadate anions, [H₃V₁₀O₂₈]³⁻, in one-dimensional vertical chains, bonded by interdecavanadate hydrogen bonds. The interchain region is populated by (H₂en)²⁺ cations and H₂O molecules, which form a network of hydrogen bonds. From the filtrate solution of the reaction mixture containing V^IVOSO₄, d,l-diaminopropionic acid and salicylaldehyde, which also contained triethylamine, a diprotonated decavanadate 3 was obtained. Compound 3 consists of decavanadate vertical dimers, surrounded by triethylamonium cations that preclude the interaction between the dimers. Bond valence calculations were used to confirm the degree of protonation of the decavanadate anions.     

Resolution of enantiomers by HPLC on tris(4-alkoxyphenylcarbamate)s of cellulose and amylose

Ten phenylcarbamate derivatives of cellulose and amylose having alkoxy groups such as ethoxy, isopropoxy, and isobutoxy at 4-position, and methyl groups at 3- and 5-positions and methoxy group at 4-position were synthesized and their chiral recognition abilities as stationary phases for high-performance liquid chromatography were investigated and compared to those with tris(4-methoxyphenylcarbamate)s of cellulose and amylose. In 4-alkoxy derivatives of cellulose, chiral recognition ability increased as the bulkiness of 4-alkoxy groups increased. 4-Isopropoxy and 4-isobutoxy derivatives showed high chiral recognition. On the other hand, chiral discrimination of amylose 4-alkoxy derivatives scarcely depended on the bulkiness of the alkoxy group, and 4-methoxy and 4-isopropoxy derivatives showed high chiral recognition. 3,5-Dimethyl-4-methoxyphenylcarbamates of cellulose and amylose possessed higher chiral recognition ability than the corresponding 4-methoxy derivatives. © 1993 Wiley-Liss, Inc.     

Synthesis, characterization, crystal structure and luminescence properties of phosphinic silver(I) complexes with thiourea derivatives

Reaction of phenylisothiocyanate with different aromatic amines allowed the synthesis of compounds containing the thiourea moiety. By reacting silver bis(triphenylphosphine)nitrate with suitable ligands belonging to this family of sulphurated compounds, three new complexes have been afforded. Ligands and complexes were characterized also by X-ray diffraction. The structures reveal remarkable differences in the silver coordination geometry in function of the nature and size of the ligand. The emission properties of all compounds were characterized at 10 and at 298 K.     

Design, synthesis and bioevaluation of novel maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones as cytostatic agents

A novel series of maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones were prepared to investigate the efficacy of micronutrient conjugation in enhancing cytotoxic potency by improving selectivity and delivery. These compounds, prepared as anticancer agents, were expected to demonstrate enhanced selectivity towards malignant cells through the inhibition of topoisomerase IIα via protein thiolation. The cytostatic effects of these compounds were evaluated against three cell lines, namely murine L1210 leukemia cells, human Molt 4/C8 and CEM T-lymphocyte cells. All compounds were found to have greater potency than the reference drug melphalan. Several compounds were found to potently inhibit topoisomerase IIα and displayed cytostatic activity in the nanomolar range.     

Synthesis, structures and magnetic properties of oxamido-bridged trinuclear Cu(II)-Mn(II)-Cu(II) complexes

Based on self-assembly of the dissymmetrical mononuclear entity CuL(CH₃OH) [H₂L = (E)-N¹-(2-((2-aminocyclohexydiimino)(phenyl)methyl)-4-chlorophenyl)-N²-(2-benzyl-4-chlorophenyl)oxalamide] with Mn(II), two trinuclear complexes were prepared. They are of the formula [(LCuN₃)₂Mn(CH₃OH)₂] · 2CH₃OH · 2H₂O (1) and [(LCuSCN)₂Mn(H₂O)₂] · 4CH₃OH (2). Their magnetic properties were studied by susceptibility versus temperature measurement, the best fitting of the experimental data led to J = −14.40 cm⁻¹ for 1 and J = −15.48 cm⁻¹ for 2. Hydrogen bonds help complex 1 to produce a novel S type one-dimensional chain-like supramolecular structure. In complex 2, Cl?Cl interaction also results in the formation of a one-dimensional structure.