Enzymatic Transesterification of 3,7-Dimethyl-4,7- octadien-1-ol Using Lipases

Enzymatic transesterification of (±)-3,7-dimethyl-4,7-octadien-1-ol ( 1 ) using various lipases and vinyl esters resulted in the formation of (S)-(+)-1-acyloxy-3,7-dimethyl-4,7-octadiene ((S)- 2 ) and (R)-(-)-3,7-dimethyl-4,7-octadien-1-ol ((R)- 1 ). Cyclization of (R)- 1 with iodine afforded (4R)-(-)-cis-4-methyl-2-(2-methyl-1-propenyl)tetrahydropyran ((-)-rose oxide). © 1997 SCI.     

Light-Switchable Antagonists for the Histamine H1 Receptor at the Isolated Guinea Pig Ileum

The histamine H₁ G protein-coupled receptor (GPCR) plays an important role in allergy and inflammation. Existing drugs that address the H₁ receptor differ in their chemical structure, pharmacology, and side effects. Light-controllable spatial and temporal activity regulation of photochromic H₁ ligands may contribute to a better mechanistic understanding and the development of improved correlations between ligand structure and pharmacologic effects. We report photochromic H₁ receptor ligands, which were investigated in an organ-pharmacological assay. Initially, five photochromic azobenzene derivatives of reported dual H₁–H₄ receptor antagonists were designed, synthesized, photochemically characterized, and organ-pharmacologically tested on the isolated guinea pig ileum. Among them, one compound [trans- 19 : (Z)-1-(4-chlorophenyl)-1-(4-methylpiperazin-1-yl)-N-(4-((E)-phenyldiazenyl)phenyl)methanimine] retained the antagonistic activity of its non-photochromic lead, and trans–cis isomerization by irradiation induced a fourfold difference in the pharmacological response. Further structural optimization resulted in two bathochromically shifted derivatives of 19 [NO₂-substituted 35 {(Z)-1-(4-chlorophenyl)-1-(4-methylpiperazin-1-yl)-N-(4-((E)-(4-nitrophenyl)diazenyl)phenyl)methanimine} and SO₃⁻-substituted 41 {4-((E)-(4-(((Z)-(4-chlorophenyl)(4-methylpiperazin-1-yl)methylene)amino)phenyl)diazenyl)benzenesulfonate}], which do not require the use of UV light for photoisomerization and which also have improved solubility and show reduced tissue impairment. The trans isomers of both compounds showed a remarkable increase in antagonistic activity relative to their lead trans- 19 ; furthermore, a 46-fold difference in activity on the isolated guinea pig ileum was observed between trans- and cis- 35 .     

Synthesis,Characterization and Anti-Breast Cancer Activity of New 4-Aminoantipyrine-Based Heterocycles

4-Aminoantipyrine was utilized as key intermediate for the synthesis of pyrazolone derivatives bearing biologically active moieties. The newly synthesized compounds were characterized by IR, ¹H- and ¹³C-NMR spectral and microanalytical studies. The compounds were screened as anticancer agents against a human tumor breast cancer cell line MCF7, and the results showed that (Z)-4-((3-amino-5-imino-1-phenyl-1H-pyrazol-4(5H)-ylidene)methylamino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 5, 3-(4-bromophenyl) -1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 13, 1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1-Hpyrazol- 4-yl)-3-(4-iodophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 14, 3,3′-(4,4′-sulfonylbis(4,1-phenylene))bis(1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol- 4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile) 16, (Z)-1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-hydrazono-4-oxo-3-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 17, (Z)-1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-3-phenyl-2-(2-phenylhydrazono)-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile 18, and (Z)-4-(3-amino-6-hydrazono-7-phenyl-6,7-dihydro pyrazolo[3,4-d]pyrimidin-5-yl)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 19 were the most active compounds with IC₅₀ values ranging from 30.68 to 60.72 μM compared with Doxorubicin as positive control with the IC₅₀ value 71.8 μM.     

The synthesis,characterization, electrochemical character,catalytic and antimicrobial activity of novel,azo-containing Schiff bases and their metal complexes

Three novel Schiff base ligands containing the azo group, 2-((E)-(4-((E)-phenyldiazenyl)phenylimino)methyl)phenol, 3-((E)-(4-((E)-phenyldiazenyl)phenylimino)methyl)benzene-1,2-diol and 4-((E)-(4-((E)-phenyldiazenyl)phenylimino)methyl)benzene-1,2,3-triol, were synthesized from the reaction of p-aminoazobenzene with salicylaldehyde, 2,4-dihydroxybenzaldehyde and 2,3,4-trihydroxybenzaldehyde, respectively. The mononuclear Co(II) and Cu(II) complexes of the Schiff base ligands were prepared and characterized using elemental analyses, IR, UV–visible spectroscopy, magnetic susceptibility and conductance measurements; ¹H NMR and mass spectra of the ligands were also recorded. The Co(II) and Cu(II) metal complexes are formed by the coordination of the N and O atoms of the ligands. The electrochemical properties of the metal complexes were investigated at 100 mV s^?1 scan rate in DMSO; the oxidative C–C coupling properties of the Co(II) and Cu(II) complexes were investigated on the sterically hindered 2,6-di-tert-butylphenol (DTBP). In addition, the Schiff base ligands and their complexes were evaluated for both their in vitro antibacterial activity using the disc diffusion method.     

[18F]PRIMATX,a New Positron Emission Tomography Tracer for Imaging of Autotaxin in Lung Tissue and Tumor-Bearing Mice

Autotaxin (ATX) is a secreted enzyme with tissue levels associated with tissue injury, which increase during wound healing and chronic fibrotic diseases. We selected [¹⁸F](R,E)-3-(4-chloro-2-((5-methyl-2H-tetrazol-2-yl)methyl)phenyl)-1-(4-((5-(2-fluoroethoxy)pyridin-2-yl)methyl)-2-methylpiperazin-1-yl)prop-2-en-1-one ([¹⁸F]PRIMATX, [¹⁸F] 2 ), a tracer for positron emission tomography, to image ATX expression in vivo. It successfully differentiates expression levels in lung tissue samples from idiopathic pulmonary fibrosis patients, and allows the detection of ATX-expressing tumors in living mice, confirming its potential for development as a clinical imaging agent.     

Coupling of cyclohexene oxide (CHO) and carbon disulfide (CS2) catalyzed by the asymmetric bis-Schiff-base Zn(II) complex

Based on the self-assembly of the asymmetric bis-Schiff-base ligand H₂L (H₂L = 4-((E)-(2-((E)-3,5-dibromo-2-hydroxybenzylideneamino)phenylimino)(phenyl)methyl-1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-ol) and Zn(OAc)₂·2H₂O, a new [Zn(L)] (1) was obtained and shown to efficiently catalyze the coupling of CHO (cyclohexene oxide) and CS₂ (carbon disulfide) in activation with [PPN]Cl (PPN⁺ = bis(triphenylphosphoranyidene)-ammonium), n-Bu₄NBr or n-Bu₄NI, where both poly[thio]carbonates and cyclic [thio]carbonates were produced, and the strong O/S exchange afforded the limited formation of trithiocarbonate in the cyclic [thio]carbonate byproducts.     

Preparation and characterization of a novel host (zeolite NaY)/guest (copper(II) complex of a new bidentate Schiff base ligand) nanocomposite material (HGNM): a comparison between catalytic reactivity of free and encapsulated complexes in oxidation of benzyl alcohol and aldol condensation

A copper(II) complex of 4-((E)-(4-(1H-benzo[d]imidazol-2-yl)phenyl)diazenyl)-2-((E)-(4-hydroxyphenylimino) methyl)phenol (HL) was encapsulated in zeolite NaY by flexible ligand method. The structure of encapsulated complex was characterized by spectroscopic (electronic and FT-IR), XRD, TGA, BET and elemental analysis data. Furthermore, catalytic activity of the neat and encapsulated complexes was studied in oxidation of benzyl alcohol and aldol condensation. The encapsulated complex was more reactive and stable than the corresponding free complex. Nanocomposite material was enough stable to be reused for several times. Finally, the reaction parameters were optimized for oxidation of benzyl alcohol and aldol condensation.     

Phosphorescent,green-emitting Ir(III) complexes with carbazolyl-substituted 2-phenylpyridine ligands: Effect of binding mode of the carbazole group on photoluminescence and electrophosphorescence

The ligands, 9-((6-phenylpyridin-3-yl)methyl)-9H-carbazole and 9-(4-(pyridin-2-yl)benzyl)-9H-carbazole were synthesized by attaching a carbazolyl group to the pyridine and phenyl rings of 2-phenylpyridine, respectively. Ir(III) complexes were prepared by a simple procedure and the solubility of the novel complexes was significantly better than that of the conventional, green-emitting conventional fac-tris(2-phenylpyridinato-C²,N)iridium(III). The Ir(III) complexes were used to prepare electrophosphorescent polymer light-emitting devices. The device comprising 10% of fac-tris(2-(4′-((9H-carbazol-9-yl)methyl)phenyl)pyridinato-C²,N)iridium(III) exhibited an external quantum efficiency of 7.88%, luminous efficiency of 23.01 cd/A, and maximum brightness of 32,640 cd/m². The color of the emissions of fac-tris(2-(4′-((9H-carbazol-9-yl)methyl)phenyl)pyridinato-C²,N)iridium(III) was similar to that of conventional fac-tris(2-phenylpyridinato-C²,N)iridium(III). This work shows that integration of a rigid hole-transporting carbazole and phosphorescent complex in one molecule provides a new route to highly efficient, solution-processable complexes for electrophosphorescent applications.     

A new family of trinuclear Ru(II) polypyridyl complexes acting as pH-induced fluorescence switch

Tripodal ligands 1,3,5-tris{4-((1,10-phenanthroline-[5,6-d]imidazol-2-yl)phenoxy)methyl}-2,4,6-trimethylbenzene (L¹), 1,1,1-tris{4-((1,10-phenanthroline-[5,6-d]imidazol-2-yl)phenoxy)methyl}propane (L²), 2,2′,2′′-tris{4-((1,10-phenanthroline-[5,6-d]imidazol-2-yl)phenoxy)ethyl}amine (L³), and corresponding Ru(II) complexes [(bpy)₆L^1–3(Ru^II)₃](PF₆)₆, shortly called (Ru–L^1–3), have been synthesized. UV–vis absorption and fluorescence spectra of these complexes are both strongly dependent on the pH of the buffer solution. These complexes act as pH-induced off–on–off fluorescence switch through protonation and deprotonation of the imidazole-containing ligands.     

The synthesis and photophysical studies of quinoxaline and pyridopyrazine derivatives

A simple and facile method for the synthesis of 2,3-bis[(E)-2-aryl vinyl]-quinoxaline and 2,3-bis[(E)-2-aryl vinyl]-pyrido(2,3-b)pyrazine is described. Condensation of cinnamils with 1,2-diaminobenzene and 2,3-diaminopyridine in water using conventional heating and microwave irradiation afforded high yields (71–92%) of 2,3-bis[(E)-2-aryl vinyl]-quinoxalines and 2,3-bis[(E)-2-arylvinyl]-pyrido(2,3-b)pyrazines. The photophysical properties of the resultant quinoxaline and pyrazine derivatives were studied; the pyridopyrazine derivatives were found to exhibit halochromism.     

In situ synthesis and dielectric properties of copper(II) and nickel(II) chiral Schiff base complexes

Two chiral Schiff base-containing complexes, [Cu(L¹)](ClO₄)₂·H₂O (1, L¹ = (S,S)-N1,N2-bis((1H-imidazol-4-yl)methylene)cyclohexane-1,2-diamine) and [Ni(L²)₂](ClO₄)₂ (2, L² = (S,S)-N1-((1H-imidazol-4-yl)methylene)cyclohexane-1,2-diamine) were synthesized from the reaction mixture of 1H-imidazole-4-carbaldehyde, (S,S)-1,2-diaminocyclohexane and Cu(ClO₄)₂·6H₂O or Ni(ClO₄)₂·6H₂O in methanol. Single-crystal X-ray diffraction analyses reveal that the in situ generated chiral Schiff base ligands L¹ and L² are bisubstituted and monosubstituted, respectively, corresponding to the different metal ions Cu^II and Ni^II. Variable-frequency and -temperature dielectric properties of 1 and 2 have been studied.     

Synthetic Chalcones with Potent Antioxidant Ability on H2O2-Induced Apoptosis in PC12 Cells

Chalcone derivatives (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one and (E)-3-(4-hydroxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one (Compounds 1 and 2) have been demonstrated to be potent anti-inflammatory agents in our previous study. In light of the relationship of intracellular mechanisms between anti-inflammatories and antioxidants, we further designed and synthesized a series of chalcone derivatives based on 1 and 2, to explore their antioxidant efficacy. The majority of the derivatives exhibited strong protective effects on PC12 (PC12 rat pheochromocytoma) cells exposed to H₂O₂, and all compounds were nontoxic. A preliminary structure-activity relationship was proposed. Compounds 1 and 1d ((E)-2-methoxy-4-(3-(4-methoxyphenyl)-3-oxoprop-1-en-1-yl) phenyl acrylate) exerted the action in a good dose-dependent manner. Quantitative RT-PCR (qRT-PCR) and western blot analysis showed that 1 and 1d significantly improve the expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2)-dependent antioxidant genes g-Glutamylcysteine Ligase Catalytic Subunit (GCLC) and heme oxygenase-1 (HO-1) and their corresponding proteins (γ-glutamyl cysteine synthase (γ-GCS) and HO-1) in PC12 cells. Inhibition of GCLC and HO-1 by specific inhibitors, l-buthionine-S-sulfoximine (BSO) and zinc protoporphyrin (ZnPP), respectively, partially reduce the protective effect of 1 and 1d. These data present a series of novel chalcone analogs, especially compounds 1 and 1d, as candidates for treating oxidative stress-related disease by activating the Nrf2-antioxidant responsive element (ARE) pathway.     

Optical properties and aggregation of novel azo-dyes bearing an end-capped oligo(ethylene glycol) side chain in solution,solid state and Langmuir–Blodgett films

Optical properties and aggregation of two novel azo-dyes N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(3,6,9-trioxadecas-1-yl)amine (RED-PEGM-3) and N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl] phenyl}-N-(3,6,9,12,15,18,21,24-octaoxapentaeicos-1-yl)amine (RED-PEGM-8) were studied by UV–vis spectroscopy in solution, solid state and Langmuir–Blodgett films. The results were compared to those obtained for their precursor 1-amino-4′-nitroazobenzene (Disperse Orange 3, DO3) and 1-N-methylamino-4′-nitroazobenzene (RED-H). Increasing the polarity of methanol:water mixtures gave rise to the formation of H-aggregates for all dyes. Similar aggregates were also detected in cast films. NOESY, 2D ¹H NMR experiments carried out in aqueous solutions of RED-PEGM-8 revealed the formation of atypical antiparallel H-aggregates. Only RED-PEGM-3 gave traces of J-aggregates in the solid state. RED-PEGM-3 and RED-PEGM-8 readily form J-aggregates in Y-type Langmuir–Blodgett films.     

Mechanism of Antiradical Activity of Newly Synthesized 4,7-Dihydroxycoumarin Derivatives-Experimental and Kinetic DFT Study

Coumarin derivatives have proven beneficial biological activities, but the mechanism of their radical scavenging potency is not fully understood. In this study, the antiradical capacity of two newly synthesized 4,7-dihydroxycoumarin derivatives: (E)-3-(1-((3-hydroxy-4-methoxyphenyl)amino)-ethylidene)-2,4-dioxochroman-7-yl acetate (A-3OH) and (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (A-4OH) towards HO^• were examined by Electron Paramagnetic Resonance (EPR) Spectroscopy and Density Functional Theory (DFT). The compounds were fully characterized by the elemental microanalysis, IR, and NMR spectroscopies. The effect of pH on the acid–base equilibria is separately discussed and the predominant species at the physiological pH were determined. Several common mechanisms (Hydrogen Atom Transfer (HAT), Single-Electron Transfer followed by Proton Transfer (SET-PT), Sequential Proton Loss followed by Electron Transfer (SPLET), Radical Adduct Formation (RAF), and Intramolecular Hydrogen Atom Abstraction (iHAA)) of radical scavenging were investigated based on thermodynamic and kinetic parameters. EPR results indicated that both compounds significantly reduce the amount of present HO^•. The results of the kinetic DFT study demonstrated that both compounds predominantly exhibit antiradical capacity through HAT and SPLET mechanisms. The estimated overall rate constants (k_overall) proved that A-4OH shows better antioxidant capacity than A-3OH which is well-correlated with the results obtained by EPR measurement.     

Sensing metal ions with two new azomethine–thiophene pincer ligands (NSN): Fluorescence and MALDI-TOF-MS applications

The two new pincer azomethine–thiophene ligands (N,NE′,N,NE′)-N,N′-(thiophene-2,5-diylbis(methan-1-yl-1-ylidene))bis(naphathalen-2-ylmethanamine) (L1) and (E)-(4,6-dihydropyren-1-yl)-N-((5-((E)-(pyren-1-ylmethylimino)ethyl)thiophen-2-yl)methylene)methanamine (L2), their absorption, fluorescence and MALDI-TOF-MS spectroscopic studies are described. The two systems synthesised combine the emissive probes pyrene and naphthyl with the good chelating properties of a tridentate SN₂ donor-set from a thiophene Schiff-base ligand. Both ligands gave analytically pure solid complexes with Ni(II) and Pd(II) salts. The bichromophoric pyrene derivative L2 presents two emission bands in solution, one corresponding to the monomer species and a red-shifted band attributable to the intramolecular excimer. Ni(II) and Pd(II) complexation affects the conformation in solution, increasing the monomer emission at the expense of the excimer band; this effect could be explored in metal ion sensing. System L1 behaves as a non emissive probe. In situ complexation reactions followed by MALDI-TOF-MS spectrometry without matrix support have also been performed; these experiments show that L1 could be a potential chemosensor for Ni(II) and Pd(II).     

Preparation and characterization of novel grafted polyethylene based azo-polymers bearing oligo(ethylene glycol) spacers

Novel grafted azo-polymers were prepared from commercial low density polyethylene plates (PE). First, precursor polymers were synthesized by reacting PE in the presence of acryloyl chloride using gamma radiation. Further esterification of the resulting grafted polymers with four new amino-nitro substituted azobenzene derivatives bearing oligo(ethylene glycol) segments: N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(5-hydroxy-3-oxapentas-1-yl)amine (RED-PEG-2), N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(8-hydroxy-3,6-dioxaoctas-1-yl)amine (RED-PEG-3), N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(11-hydroxy-3,6,9-trioxaundecas-1-yl)amine (RED-PEG-4) and N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(17-hydroxy-3,6,9,12,15-pentaoxaheptadecas-1-yl)amine (RED-PEG-6) led to the formation of branched azo-polymers. These polymers were characterized and their thermal and optical properties were studied. Besides, the influence of the irradiation dose, irradiation time and the structure of the dyes on the properties of the obtained polymers are discussed.     

Synthesis and characterization of Cu(I) and Zn(II) complexes with new sulfur-bearing isoxazole- or pyrazole-based ligands

The synthesis of the new ligands 6-(5-methyl-1,2-oxazol-3-yl)-2,3-dihydro-5H-[1,4] dithiino[2,3-c]pyrrole-5,7(6H)-dione (isox′) and 6-(3-methyl-1H-pyrazol-5-yl)-2,3-dihydro-5H-[1,4]dithiino[2,3-c]pyrrole-5,7(6H)-dione (pyraz′) and their coordination chemistry toward Cu(I) and Zn(II), was studied. The ligands and their complexes were characterized using a combination of either multinuclear NMR (¹H and ¹³C{¹H}), HRMS, FTIR or Uv–Vis spectroscopy. The solid state structures of ligand isox′ and complexes [Cu(pyraz′)₂]OTf and [Zn(OOCCF₃)₂(pyraz′)₂] were determined. Interestingly, isox′ presents a yellow luminescence in its free form. Additionally, the ability of isox′ to coordinate as an N–O bidentate ligand or as an N–S bridge between two copper centers, forming a coordination polymer, is studied. The solid state structure of this Cu(I)-isox′ 1D coordination polymer is also reported.     

A lanthanide azametallacrown with aza10-MC − 4 motif: Structure and single molecule magnetism behavior

A rare lanthanide-containing azametallacrown with structural formula [Er₄(μ₃-OH)₂(ppt)₄(H₂ppt)₂(OAc)₂]·2DMF (1) (H₂ppt = 3-(2-hydroxyphenyl)-5-(pyrazin-2-yl)-1,2,4-triazole) has been reported. X-ray crystallographic analysis exhibits a remarkable aza10-MC-4 structural motif with the ring having [Er–N–N–Er–O] connectivity. Measurements of dc magnetic susceptibility and isothermal magnetization reveal the strong magnetic anisotropy, and ac susceptibility shows slow magnetization relaxation at a dc field of 2000 Oe.     

A Green Synthesis of Fused Polycyclic 5H-Chromeno[3,2-c]quinoline-6,8(7H,9H)-dione Derivatives Catalyzed by TsOH in Ionic Liquids

A three-component reaction of benzaldehyde, 5,5-dimethyl-3-(arylamino)cyclohex-2-enone and 4-hydroxyquinolin-2(1H)-one gave a series of 3-((4,4-dimethyl-6-oxo-2-(arylamino) cyclohex-1-en-1-yl)(aryl)methyl)-4-hydroxyquinolin-2(1H)-one derivatives in ionic liquids at 80°C under catalyst-free conditions. In the presence of TsOH at 140°C, the same reaction provided an efficient method for the synthesis of 7-aryl-10,10-dimethyl-10,11-dihydro-5H-chromeno[3,2-c] quinoline-6,8(7H,9H)-dione derivatives in high yields while aromatic amine losing unexpectedly.     

Divalent cobalt,zinc, and copper coordination polymers based on a new bifunctional ligand: Syntheses,crystal structures,and properties

Three new coordination polymers, namely, [ML(H₂O)]_n (M = Co (1), Zn (2)) and [CuL(DMF)]_n (3), have been hydrothermally synthesized through the reaction of bifunctional ligand 5-((2-methyl-1H-imidazol-1-yl)methyl)benzene-1,3-dioic acid (H₂L) with divalent cobalt, zinc and copper salts, and structurally characterized by elemental analysis, IR and X-ray diffraction. Both complexes 1 and 2 are two-fold interpenetration 3D frameworks. Complex 3 exhibits (3,6)-connected framework with (4.6²)₂(4².6¹⁰.8³) topology. Furthermore, UV–vis absorption spectra and powder X-ray diffraction (PXRD) were investigated as well.