Synthesis and biological evaluation of a series of novel salicylanilides as inhibitors of EGFR protein tyrosine kinases

The synthesis and biological evaluation of two series of salicylanilide derivatives on the EGFR and ErbB-2 tyrosine kinases inhibitory activities were conducted.Of the tested compounds those having an additional aryl group substituted on the anilino ring were active on the EGFR tyrosine kinase inhibition(7a-c and 13a,13c,13d,13f).The inhibitory activities were all in the low micromolar or submicromolar range.In addition,compound 13a was found to have dual inhibitory activities both on EGFR and ErbB-2 tyrosine kinases(1.654±1.280 and 7.134±1.265μmol/L).     

Peptidic alpha-ketocarboxylic acids and sulfonamides as inhibitors of protein tyrosine phosphatases

One common approach for designing protein tyrosine phosphatase (PTPase) inhibitors is to incorporate a nonhydrolyzable phosphotyrosine (pTyr) mimic into a peptide substrate for PTPases. This report describes the synthesis of three such nonhydrolyzable pTyr mimics that contain alpha-ketoacid, alpha-hydroxyacid, and methylenesulfonamide functional groups in place of the phosphate. These pTyr mimics were incorporated into the peptide sequence Ac-Asp-Ala-Asp-Glu-X-Leu-NH(2), where X is the pTyr mimic, and analyzed for activity against the Yersinia PTPase and PTP1B.     

Redox induced pH-switch of Tb(III) centered luminescence of Tb(III) complex with p-sulfonatothiacalix[4]arene

The reversible redox switching of Tb(III) centered luminescence resulting from the protonation/deprotonation of the ligand has been realized. The redox couple quinone/hydroquinone serves as a proton pump, leading to the reversible protonation/deprotonation of the phenolate groups of p-sulfonatothiacalix[4]arene and following decomplexation/complexation with Tb(III) ion in aqueous solution.     

Squaric acids: a new motif for designing inhibitors of protein tyrosine phosphatases

[structure: see text] Protein tyrosine phosphatases (PTPases) are important targets in medicinal chemistry. These enzymes play a role in a number of human diseases, including type II diabetes and infection by Yersinia pestis, the causative agent of bubonic plague. Derivatives of squaric acids such as 2-aryl-1-hydroxycyclobut-1-ene-3,4-diones represent a new class of monoanionic inhibitors for PTPases.     

Preparation, photo- and electro-luminescent properties of a novel complex of Tb (III) with a tripod ligand

A novel Tb(III) complex TbL (L=tris[2-(2-carboxyphenoxy)ethyl]amine, H3L) was synthesized and characterized by means of elemental analyses, IR spectra, thermal analyses, and molar conductivity measurement. The photoluminescent properties of the complex were investigated. In addition, PVK doping Tb(III) complex was fabricated as the emissive layer by spin-coating and its electroluminescent properties were studied, in which the structure of the device was ITO (indium tin oxide)/PVK (polyvinylcarbazole)/PVK: TbL/PBD (2-(4-biphenylyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole)/LiF/Al. It was indicated that pure green and narrow bandwidth emission at 545nm from photoluminescence of TbL complex film and the organic electroluminescent device is the characteristic emission of Tb(III) ion, and the electroluminescence spectrum of the device was very similar to that of the photoluminescence of TbL complex film. The lowest triplet level of the ligand was calculated from the phosphorescence spectrum of GdL in N,N-dimethyl formamide (DMF) dilute solution determined at 77K, and the energy transfer mechanisms in TbL complex were discussed.     

Visible-light sensitisation of Tb(III) luminescence using a blue-emitting Ir(III) complex as energy-donor

In Ir(III)/Tb(III) dyads in which the excited state energy of the Ir(III) unit lies above 22,000 cm(-1), visible-light excitation of the Ir(III) chromophore results in sensitised emission from Tb(III) following Ir → Tb energy-transfer.     

Rapid assembly and in situ screening of bidentate inhibitors of protein tyrosine phosphatases

[reaction: see text] We have successfully designed and synthesized a small library of protein tyrosine phosphatase (PTP) inhibitors, in which the so-called "click chemistry" or Cu(I)-catalyzed 1,3-dipolar alkyne-azide coupling reaction was carried out for rapid assembly of 66 different bidentate compounds. Subsequent in situ enzymatic screening revealed a potential PTP1B inhibitor (IC(50) = 4.7 microM) which is 10-100 fold more potent than other PTPs.     

Investigation of ion binding in ionic polysaccharide solutions using Tb(III) as a luminescent probe

The luminescence properties of a series of lanthanide-substituted ionic polysaccharides have been examined in an attempt to learn about the nature of interactions between the metalions and the polymers. Emission and excitation spectra were obtained for Tb(III) complexes with carboxymethyl cellulose, Sclerox S-1.0, alginate, polygalacturonic acid, amylose sulfate, dextran sulfate, and i-carrageenan. Studies of the chirality associated with the metal-ion binding sites were performed through the use of circularly polarized luminescence spectroscopy. It was learned that the lanthanide ions could form complexes with polysaccharides in the electrostatic manner of polyelectrolytes, and that specific ligating groups could further influence the metal-ion binding characteristics.     

Octadentate cages of Tb(III) 2-hydroxyisophthalamides: a new standard for luminescent lanthanide labels

The synthesis, structure, and photophysical properties of several Tb(III) complexes with octadentate, macrotricyclic ligands that feature a bicapped topology and 2-hydroxyisophthalamide (IAM) chelating units are reported. These Tb(III) complexes exhibit highly efficient emission (Φ(total) ≥ 50%), large extinction coefficients (ε(max) ≥ 20,000 M(-1) cm(-1)), and long luminescence lifetimes (τ(H(2)O) ≥ 2.45 ms) at dilute concentrations in standard biological buffers. The structure of the methyl-protected ligand was determined by single-crystal X-ray diffraction and confirms the macrotricyclic structure of the parent ligand; the amide groups of the methyl-protected cage compound generate an anion binding cavity that complexes a chloride anion. Once the ligand is deprotected, a conformational change generates a similar cavity, formed by the phenolate and ortho amide oxygen groups that strongly bind lanthanide ions. The Tb(III) complexes thus formed display long-term stability, with little if any change in their spectral properties (including lifetime, quantum yield, and emission spectrum) over time or in different chemical environments. Procedures to prepare functionalized derivatives with terminal amine, carboxylate, and N-hydroxysuccinimide groups suitable for derivatization and protein bioconjugation have also been developed. These bifunctional ligands have been covalently attached to a number of different proteins, and the terbium complexes' exceptional photophysical properties are retained. These compounds establish a new aqueous stability and quantum yield standard for long-lifetime lanthanide reporters.     

Lanthanide directed self-assembly formations of Tb(III) and Eu(III) luminescent complexes from tryptophan based pyridyl amide ligands

The formation of self-assembly complexes between the ligands 1 (SS) and 2 (RR) and terbium or europium was undertaken and shown (using various spectroscopic titrations) to give rise to the exclusive formation of 2:1 (L:Ln) stoichiometry and not the anticipated 3:1 stoichiometry.     

酪氨酸蛋白激酶抑制剂:亚苄基丙二腈类衍生物定量构效关系的量子化学研究

用量子化学从头算方法,对亚苄丙二腈衍生物的定量构效关系(QSAR)进行了研究,结果显示:指示变量I,偶极矩Dipole和最低空轨道的能量ELUMO对亚苄丙二腈衍生物的抑制活性有很大影响,回归分析得到了相关性好的相关模型(R=0.95).I=0时,亚苄基丙二腈类衍生物的抑制作用由其化学反应性决定;I=1时其抑制作用由其静电性决定.     

Conversion of molecular information by luminescent nanointerface self-assembled from amphiphilic Tb(III) complexes

A novel amphiphilic Tb(3+) complex (TbL(+)) having anionic bis(pyridine) arms and a hydrophobic alkyl chain is developed. It spontaneously self-assembles in water and gives stable vesicles that show sensitized luminescence of Tb(3+) ions at neutral pH. This TbL(+) complex is designed to show coordinative unsaturation, i.e., water molecules occupy some of the first coordination spheres and are replaceable upon binding of phosphate ions. These features render TbL(+) self-assembling receptor molecules which show increase in the luminescence intensity upon binding of nucleotides. Upon addition of adenosine triphosphate (ATP), significant amplification of luminescent intensity was observed. On the other hand, ADP showed moderately increased luminescence and almost no enhancement was observed for AMP. Very interestingly, the increase in luminescence intensity observed for ATP and ADP showed sigmoidal dependence on the concentration of added nucleotides. It indicates positive cooperative binding of these nucleotides to TbL(+) complexes preorganized on the vesicle surface. Self-assembly of amphiphilic Tb(3+) receptor complexes provides nanointerfaces which selectively convert and amplify molecular information of high energy phosphates linked by phosphoanhydride bonds into luminescence intensity changes.     

Photoluminescent layered Y(III) and Tb(III) silicates doped with Ce(III)

The synthesis and structural characterization of new layered rare-earth silicates K(3)[M(1-a)Ce(a)Si(3)O(8)(OH)(2)], M = Y(3+), Tb(3+), a < 1 (AV-22 materials), have been reported. These materials combine the properties of layered silicates, such as intercalation chemistry, and photoluminescence and may find applications in new types of sensor devices. For mixed Tb/Ce-AV-22, evidence has been found for the energy transfer from the large Ce(3+) 4f( 1) --> 5d(1) broad band to the sharp Tb(3+) 4f (8) lines. This energy transfer allows the fine-tuning of the color emission in the blue-green region of the chromaticity diagram. Upon Ce(3+) excitation (342 nm), the radiance of Tb/Ce-AV-22 is approximately 2 times higher than that measured under direct Tb(3+) excitation, which reinforces the existence of effective room-temperature Ce(3+)-to-Tb(3+) energy transfer.     

具有三重螺旋链的二氯苯氧乙酸铽(Ⅲ)配位聚合物的晶体结构与荧光性质

采用水热法制备了一种新型金属配位聚合物[Tb2(2,4-D)6(2,2'-bipy)2]n(1)(2,4-D=2,4-二氯苯氧乙酸;2,2'-bipy=2,2'-联吡啶),用X-衍射单晶结构分析、红外光谱分析、荧光光谱法对产物进行了结构表征。结构分析表明,标题配合物属于单斜晶系,P2(1)/n空间群,晶胞参数a=2.792(1)nm,b=0.851(3)nm,c=3.335(1)nm,β=113.6470(1)°,V=7.2575(5)nm3,Z=4。金属离子Tb3+处于扭变的四方反棱柱构型中,金属离子之间通过配体2,4-D的羧基的桥联作用,链接成为一维三重螺旋链状配位聚合物。配合物的荧光光谱表明,配合物有望成为潜在的绿光材料。     

TG and DSC studies on Sm(III) and Tb(III) tartrates

The tartrate monohydrates of Sm(III) and Tb(III), Sm₂C₁₂H₁₂O₁₈·H₂O and Tb₂C₁₂H₁₂O₁₈·H₂O, were prepared and characterized on the basis of their elemental analysis and IR spectral studies. The thermal decompositions of these compounds, studied by TG and DSC methods, were found to follow an almost uniform pattern. Decomposition occurs in four steps. The first step involves dehydration, accompanied by partial decomposition to the oxalate, followed by conversion to the carbonate. The ultimate product in each case is the oxide M₂O₃, whereM=Sm or Tb. Reflectance spectra of the terbium compound were recorded at various stages of decomposition. The kinetics of the first decomposition step was studied by the non-isothermal method. TG and DSC data for this step were analysed for the evaluation of various kinetic parameters. Reasonable values ofE, Z, andΔS ⁺ were obtained.α vs. T curves were drawn on the basis of the TG and DSC data. The results suggest that the mechanism involves random nucleation.     

Anion dependent self-assembly of "tetra-decker" and "triple-decker"luminescent Tb(III) salen complexes

The Schiff base complexes [Tb3L4(H2O)2]Cl and [Tb3L3(OAc)2Cl] both have unusual multi-decker architectures formed via intramolecular pi-pi interactions between phenylene units.     

一种吡啶酰胺类配体与Tb(Ⅲ)配位模式的探讨

研究了Tb(Ⅲ)对配体N,N-二(2-羧基苯基)-2,6-吡啶二甲酰胺(BCPD)的乙醇溶液的荧光滴定光谱,结果发现滴定过程中两者之间可能存在两种结合模式[(BCPD)_2Tb和(BCPD) Tb]。通过进一步研究配体BCPD的荧光发射光谱和时间扫描荧光分析Tb(Ⅲ)的特征光谱,从不同角度证明了两种不同配位模式的存在并分析了原因。研究结果进一步丰富和完善了稀土有机配合物的配位理论,对荧光材料的制备具有一定指导意义。     

Piezochromic luminescent (PCL) behavior and aggregation-induced emission (AIE) property of a new cationic iridium(III) complex

A new cationic Ir(III) complex based on a dendritic ancillary ligand has been designed and synthesized, which simultaneously exhibits piezochromic luminescent (PCL) behavior and aggregation-induced emission (AIE) property for the first time.     

On the role of the ground state Tb(III)/acetylacetone complex in sensitized emission of Tb(III) in ethanol solution

Summary The Tb(III)-acetylacetone system in ethanol solution has been studied by spectroscopic methods. The formation of a Tb(III)/acetylacetone (1:1) complex in the ground state has been proved and its stability constant determined,K=(0.97±0.06)·10⁴dm³mol^–1. The role of this complex in the spectrofluorimetric determination ofLn(III) ions in the presence of acetylacetone has been discussed.

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Über die Rolle eines Tb(III)-Acetylaceton-Komplexes im Grundzustand in der sensibilisierten Emission von Tb(III) in Ethanol-Lösung

Zusammenfassung Das Tb(III)-Acetylaceton-System in Ethanol-Lösung wurde mit spektroskopischen Methoden untersuchung. Die Bildung eines Tb(III)-Acetylaceton(1:1)-Komplexes im Grundzustand wurde bestätigt und seine Stabilitätskonstante bestimmt,K=(0.97±0.06)·10⁴dm³mol^–1. Die Rolle dieses Komplexes in der spektrofluorimetrischen Bestimmung vonLn(III)-Ionen in Gegenwart von Acetylaceton wurde erörtert.