Synthesis and characterization of copper-specific tetradendate ligands as potential treatment for Alzheimer's disease

To regulate copper homeostasis for the therapy of Alzheimer's disease, a series of “tetradendate monoquinoline” (TDMQ) ligands consisting of an 8-aminoquinoline nucleus with a bidentate amine side chain attached at the C2 position of the quinoline moiety, both parts being able to take part in copper chelation, were designed. These TDMQ ligands are potentially able to provide the square planar tetradentate coordination sphere, which is preferred for the extraction of copper(II) from amyloids, with a lower as possible molecular weight, to optimize the passage through different physiological barriers.     

Complexes of 8-Aminoquinoline. I. The Infrared Spectra of the Ligand,the Tris Complexes of Iron,Cobalt and Nickel Perchlorates and Their ND2 Analogues

Abstract

Deuteration of 8-aminoquinoline (aq) at the amino groups and comparison of the infrared spectrum of aq with those of aniline and quinoline enables reliable assignments to be proposed for the amino stretching and bending modes and the internal modes of the aminoquinoline rings. The spectra of the tris(8-aminoquinoline) complexes of iron, cobalt and nickel perchlorates have been examined over the range 4000–50 cm^?1 with assignments based on the ligand study and the effects of metal ion substitution and deuteration of the nickel complex. The existence of two vM-NH₂ and two vM-N(aq) bands is consistent with facial (cis-cis) octahedral coordination about the metal ion.     

Synthesis, structure and characterization of binuclear copper(Ⅱ) complexes

At room temperature, dibenzoyl peroxide undergoes oxidative addition reaction with metallic copper powder and pyridine N-oxide (triphenylphosphine oxide or 2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolin) which affords the last products as binuclear copper(II) complexes, [Cu(C5H5NO)-(C6H5COO)2]2(1), [Cu(OPPh3)(C6H5COO)2]2(2) and [Cu(C6H5COO)(C26H2oN2)](3, C26H2oN2 is 2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolin). The structure of the complexes were characterized by elemental analyses, IR spectra, TG-DTA and magnetic property. Crystals(1) are triclinic, space group P1,a=0.92617(36),b=1.06973(17), c=1.08813(29) nm, a=59.60(2)°, β=74.83(3)°,γ=72.80(2)°, V=0.880 nm3, Dc=1.520 g/cm3, Z=1, R=0.044, Rw=0.048, Mr=805.78, 3477 reflections with I > 3σ(I). Each copper(Ⅱ) ion is coordinated by two bridging bidentate benzoate ligands and one pyridine N-oxide or triphenylphosphine oxide to form dimeric binuclear molecules. The structure of the compound(1) shows a clear centre of symmetry.     

Synthesis,characterization, and crystal structure of a copper(II) complex of 1,10-phenanthroline and succinate

A mixed ligand complex of Cu(II) with 1,10-phenanthroline and succinate has been synthesized from the reaction of hydrated copper nitrate, succinate, and 1,10-phenanthroline. The nature of bonding and the structure of the complex were characterized by elemental analyses, infrared spectrum, TGA/DTA, and X-ray diffraction. The crystal crystallizes in triclinic space group P 1. The complex is polymeric and the geometry around each copper varies from square planar to distorted square pyramidal or octahedral. Each copper coordinates two oxygens of succinate and two nitrogens of 1,10-phenanthroline. The thermal decomposition of the complex has also been studied by TGA and DTA under inert atmosphere.     

Synthesis,characterization, and DNA binding of two copper(II) complexes as DNA fluorescent probes

[Cu(DAPT)₂Cl]Cl·H₂O and [Cu(DBM)(DAPT)Cl] [DAPT = 2,4-diamine-6-(pyrazin-2-yl)-1,3,5-triazine] were synthesized and characterized by IR and UV spectroscopy, elemental analysis, TG–DTA, molar conductivity, and LC–MS. The interaction with calf thymus DNA (ct-DNA) of the two complexes has been studied using UV spectra, fluorescent spectra, cyclic voltammetry, and viscosity measurements. The complexes interact with ct-DNA through classical intercalation. Fluorescence intensity changes of 1 and 2 in the absence and presence of ct-DNA have been investigated for quantitative determination of ct-DNA with the limit of detection of 3.8 and 7.7 ng mL^?1, respectively. From the result, the two complexes are potentially sensitive DNA fluorescent probes.     

Synthesis and characterization of copper(II) chelate with a new substituted bis(2-pyridyl)-amine derivative

The novel ligand, abbreviated Ibdpam, has been synthesized and characterized as well as its novel mononuclear copper(II) complex. The crystal and molecular structure of the complex [Cu^II(Ibdpam)(SO₄)(H₂O)₂]·H₂O is reported. The square-based pyramidal arrangement of the chromophore CuN₂O₃, the bidentate chelate character for the nitrogenous base, and the unidentate character of the sulfate oxy-dianion is established.     

Synthesis and electrochemical characterization of biphenyl-malonic ester substituted cobalt,copper, and palladium phthalocyanines

Phthalocyanines with four biphenyl-malonic ester groups on the periphery were synthesized by cyclotetramerization of 4-(1,1-dicarbethoxy-2-(4-biphenyl)-ethyl)-phthalonitrile. The new compounds were characterized by elemental analyses, FT-IR, ¹H NMR, ¹³C NMR, UV–Vis, and MASS spectral data. Electrochemical behaviors of novel Co(II), Cu(II), and Pd(II) phthalocyanines were investigated by cyclic voltammetry, potential differential pulse voltammetry, and applied potential chronocoulometry techniques. While Cu(II) and Pd(II) phthalocyanines give up to four common phthalocyanine ring reductions, Co(II) phthalocyanine gave two ligand-centered and two metal-centered redox processes. HOMO–LUMO gap of the complexes are comparable with the reported MPc papers.     

Synthesis,characterization, and photophysical properties of paraben substituted cyclotriphosphazenes with hydrophilic side groups

Abstract

In this study, five new paraben substituted cyclotriphosphazene compounds containing hydrophilic glycol groups were successfully synthesized. All synthesized cyclotriphosphazene compounds 1-10 were fully characterized via general spectroscopic techniques such as ¹H, ³¹P NMR and MALDI-TOF mass spectrometry. In addition, the investigations of the UV-vis absorption and fluorescence emission properties of the 1-10 carried out via absorption and fluorescence spectroscopies in different solvents. The absorbance bands of the all synthesized compounds 1-10 were observed at about 230–300?nm in all solvents studied. Furthermore, the highest fluorescence emission intensity of the compounds 1-10 was observed in tetrahydrofuran at about 312?nm and the lowest emission intensity was observed in chloroform. The synthesized molecules can be used as custom designed molecules to investigate the DNA binding properties in automatic biosensor device in our laboratories, since they carry hydrophilic glycol units for water solubility and paraben derivatives for DNA effecting properties.     

Synthesis, characterization and thermal degradation of 8-hydroxyquinoline-guanidine-formaldehyde terpolymer

Terpolymer (8-HQGF) has been synthesized using the monomers 8-hydroxyquinoline, guanidine, formaldehyde in 1:1:2 molar proportions. The structure of 8-HQGF terpolymer has been elucidated on the basis of elemental analysis and various physicochemical techniques, i.e. UV-Visible, FTIR-ATR and ¹H NMR spectroscopy. Detailed thermal degradation study of the new terpolymer has been carried out to ascertain its thermal stability. Thermal degradation curve is discussed which shows two decomposition steps (265-475 °C and 540-715 °C). Sharp-Wentworth and Freeman-Carroll methods have been used to calculate activation energies and thermal stability. The activation energy (E_a) calculated by using the Sharp-Wentworth (21.98 kJ/mol) has been found to be in good agreement with that calculated by Freeman-Carroll (23.57 kJ/mol) method. Thermodynamic parameters such as free energy change (ΔF), entropy change (ΔS), apparent entropy change (S^∗) and frequency factor (Z) have also been evaluated on the basis of the data of Freeman-Carroll method. The order of reaction (n) is found out to be 0.9979.     

8-hydroxyquinoline based neutral tripodal ionophore as a copper (II) selective electrode and the effect of remote substitutents on electrode properties

New PVC membrane ion selective electrodes based on 1,3,5-Tris(8-quinolinoxymethyl)-2,4,6-trimethylbenzene (MO8HQ) are reported. The basic sensing material belongs to the group of tripodal ionophores. Also their derivatives prepared by placing suitable substitutents at fifth position of 8-oxine moiety, i.e, 1,3,5-Tris(5-chloro-8-quinolinoxymethyl)-2,4,6-trimethylbenzene (5CHQ), 1,3,5-Tris(5-benzoyl-8-quinolinoxymethyl)-2,4,6-trimethylbenzene (5BHQ) and 1,3,5-Tris[(5-phenylhydroxymethylene)-8-quinolinoxymethyl]-2,4,6-trimethylbenzene (HYD-8HQ) ionophores have also been used to make copper-selective membrane electrodes. Among all the four electrodes, MO8HQ and HYD-8HQ ionophores based electrodes show excellent response towards Cu (II) ions. The electrodes having composition 33% PVC, 4% MO8HQ and 63% dibutyl phthalate (DBP) and 33% PVC, 6% HYD-8HQ, 63% dibutyl phthalate (DBP) exhibit a good Nernstian response to Cu (II) ions in the range of 1.0 × 10⁻⁶ to 1 × 10⁻¹ M. The electrode shows a reasonably fast response time of 15 s. The effect of pH and electrode response is also reported. It shows good selectivity for Cu (II) ions in comparison to heavy metal ions, transition metal ions and for alkali and alkaline earth metal ions. The electrode response and selectivity remains unchanged for at least 5 months. The electrode can be used as an indicator electrode in the potentiometric titration of Cu (II) ions with EDTA.     

Nanomaterials toward the treatment of Alzheimer's disease:Recent advances and future trends

Alzheimer's disease(AD) is a progressive and fatal neurodegenerative condition and the most prevalent cause of dementia. This disease is characterized by progressive cognitive impairment. The prevalence of AD is currently affecting more than 35 million people and is rising worldwide. No efficient therapy is currently available due to low drug potency and a number of various obstacles to delivery. Recent nanotechnological advancements have the potential to offer promising therapeutic options. Progress on nanomaterials as well as their applications in biomedicine is receiving increasing attention, especially the advantages of nanomaterial-based drug delivery systems. The aim of this review is to comprehensively summarize the latest developments in nanomaterial-based strategies for AD treatment, including nanoparticles, liposomes and other options for the delivery of therapeutic compounds and scaffolds for cell delivery strategies. Future research directions are also proposed. We hope this review can provide important information to guide the future development of nanomaterials in AD treatment.     

8-羟基喹啉铋的合成、表征与光谱研究

8-羟基喹啉及其衍生物是以喹啉环为母体的化合物,具有较大的共轭π键结构,吸光系数高,分子中处于邻位的羟基O和杂环N原子上都含有孤对电子,与金属离子易形成双齿配位具有特殊光学特性的五员环配合物[1-3].金属铋被认为是安全稳定的绿色重金属元素,其化合物除了广泛应用于医学外,其配合物的用途正日益被开发[4-5].本文用元素分析仪、XRD、热重-差热、红外等手段对由8-羟基喹啉形成的铋配合物的组成和结构进行表征.并初步研究了生成物的光致发光性和紫外吸收光谱.     

Synthesis,biological evaluation and Structure Activity Relationships (SARs) study of 8-(substituted)aryloxycaffeine

A series of 8-(substituted)aryloxycaffeine were prepared from 8-bromocaffeine and (substituted)phenols by modified Ullmann reaction. In vitro antibacterial activity, inhibitory activity on topoisomerase II and pharmacological activities were evaluated for the synthesized 8-(substituted)aryloxycaffeine. Among the synthesized compounds, 8-(5-chloropyridin-3-yloxy)caffeine (3k) showed strong inhibitory activity (MIC = 15.6 μg/mL) against the tested gram negative (−) bacteria Salmonella enteritidis. 8-(quinolin-8-yloxy)caffeine (3g) showed the strongest inhibitory activity against topoisomerase II. And the compounds 8-(6-methylpyridin-2-yloxy)caffeine (3j) and 8-(3-chloro-6-(trifluoromethyl)pyridin-2-yloxy)caffeine (3m) showed analgesic effect without the central nervous system stimulation.     

Synthesis,characterization, and antibacterial evaluation of copper(II) complexes supported by phenylacetic acid derivatives,and diamine ligands

Four mixed-ligand complexes, [Cu₃(cpa)₆(pda)₁] (1) (cpa = 4-chlorophenylacetic acid, pda = 1,2-diaminopropane), [Cu₃(fpa)₆(tn)₁] (2) (fpa = 4-fluorophenylacetic acid, tn = 1,3-diaminopropane), [Cu₃(cpa)₆(en)₁] (3) (cpa = 4-chlorophenylacetic acid, en = ethylenediamine), and [Cu₃(fpa)₆(pda)₁] (4) (fpa = 4-fluorophenylacetic acid, pda = 1,2-diaminopropane), were synthesized by reacting 4-chlorophenylacetic acid or 4-fluorophenylacetic acid, the diamines, and metal salts. Their structures were determined by elemental analysis and single-crystal X-ray diffraction analysis. The antimicrobial activities for the metal complexes were evaluated against Escherichia coli, Pseudomonas putida, Bacillus subtilis, and Bacillus cereus. The antimicrobial results indicated that the four synthesized complexes displayed good inhibitory activity against E. coli and B. subtilis, and could be promising antibacterial agents.     

Synthesis, characterization and emission properties of quinolin-8-olato chelated ruthenium organometallics

The reaction of Ru(RL¹)(PPh₃)₂(CO)Cl,1, with quinolin-8-ol (HQ) has afforded complexes of the type [Ru(RL²)(PPh₃)₂(CO)(Q)],3, in excellent yield (RL¹ is C₆H₂O-2-CHNHC₆H₄R(p)-3-Me-5, RL² is C₆H₂OH-2-CHNC₆H₄R(p)-3-Me-5 and R is Me, OMe, Cl). In this process, quinolin-8-olato (Q) undergoes five-membered chelation, the iminium-phenolato function tautomerizing to the imine-phenol function. In dichloromethane solution,3 displays a quasireversible3 ⁺/3 couple near 0·50 V vs SCE (3 ⁺ is the ruthenium (III) analogue of3). Coulometrically generated solutions of3 ⁺ display a strong absorption near 395 nm associated with a shoulder near 475 nm and rhombic EPR spectra withg values near 2·55, 2·13, 1·89. Solutions of3 absorb near 415 nm and emit near 510 nm at 298 K and 585 nm at 77 K. The fluorescence is believed to originate from the³MLCT state     

Synthesis,characterization, DNA interaction,cytotoxicity, and apoptosis induction of a mixed-ligand copper(II) complex

A mixed-ligand complex, [Cu(Hptc)(Me₂bpy)(H₂O)]·3H₂O (1) (H₃ptc = pyridine-2,4,6-tricarboxylic acid; Me₂bpy = 4,4′-dimethyl-2,2′-dipyridine), has been synthesized and characterized by elemental analysis, IR, and single-crystal X-ray diffraction. In the discrete mononuclear structure of 1, the copper core is in a distorted octahedral environment (CuN₃O₃) derived from tridentate chelate Hptc^2?, bidentate chelate Me₂bpy and a coordinated water. The interaction of 1 with CT-DNA was investigated by UV–vis spectra, fluorescence spectra and viscosity, which reveals that 1 binds to CT-DNA by partial intercalation. Gel electrophoresis assay demonstrated that the complex displays efficient oxidative cleavage of supercoiled DNA with H₂O₂ as an oxidant. The in vitro cytotoxicity of 1 on HeLa cells was assessed by MTT and clonogenic assay, where IC₅₀ equals 4.24 ± 0.03 μM. Fluorescence microscopic observations indicated that 1 can induce apoptosis of HeLa cells.     

Synthesis of diarylamines in the benzo[b]thiophene series bearing electron donating or withdrawing groups by Buchwald-Hartwig C-N coupling

Diarylamines in the benzo[b]thiophene series bearing electron donating or withdrawing groups, were prepared by Buchwald-Hartwig C-N coupling in moderate to high yields. The conditions used were Pd(OAc)₂ (3 mol%), BINAP as ligand (4 mol%) and Cs₂CO₃ as base (1.4 equiv.), in toluene at 100°C, being 6-bromo or amino benzo[b]thiophenes coupled, respectively, with substituted anilines or phenylbromides. The 6-aminobenzo[b]thiophene derivatives were also prepared by palladium catalyzed C-N coupling of the corresponding 6-bromo compounds with benzophenone imine, followed by acidic hydrolysis of the imino derivatives. When 4-nitrobromobenzene and 4-bromobenzonitrile were used as coupling components, triarylamines were also isolated in small amounts. The presence of a fluorine atom on the phenylbromide highly increases the diarylamine yields.     

Synthesis,characterization and luminescent properties of three-coordinate copper(I) halide complexes containing diphenylamino monodentate phosphine ligand

Three-coordinate copper halide complexes with a bidentate phosphine ligand have received much attention. Here, a series of three-coordinate dinuclear copper halide complexes containing a diphenylamino monodentate phosphine ligand, [CuX(dpnp)]₂ (dpnp = N-[2-(diphenylphosphino)-4,5-dimethylphenyl]-N-phenylaniline, X = I (1), Br (2) and Cl (3)), were synthesized, and their molecular structures and photophysical properties were investigated. The structural analysis reveals that two copper(I) centers are bridged by two halogen ligands to form a dinuclear structure with a four-membered Cu₂X₂ ring. Crystal structures of 1–3 contain 1-D supramolecular arrays constructed by intermolecular C–H?π interactions. These complexes exhibit blue emission in the solid state at room temperature and have peak emission wavelengths at 483–487 nm with microsecond lifetimes (τ = 13.9–38.1 μs) and low emission quantum yields (<0.01%). The emission of complex 1 mainly originates from intraligand (IL) transition, whereas the emissions of complexes 2 and 3 are from a combination of MLCT, XLCT and IL transitions. The three complexes displayed good thermal stability.     

Synthesis,characterization, crystal structure and non-isothermal dehydration kinetics of a copper(II) complex

A three-dimensional complex, [CuL₂(H₂O)]₂ (HL?=?3-hydroxy-1-adamantanecarboxylic acid), C₄₄H₆₄Cu₂O₁₄, was synthesized under hydrothermal conditions from CuCO₃?·?Cu(OH)₂ and HL. The crystal structure of the complex was determined by X-ray crystallography and its thermal behavior and IR spectra examined. The non-isothermal dehydration kinetics of the complex were investigated using the Achar differential method.