CoMFA and CoMSIA studies on 1,3-bis(benzylidene)-3,4-dihydro-1H-naphthalen-2-one, 2,6-bis(benzylidene)cyclohexanone, and 3,5-bis(benzylidene)-4-piperidone series of cytotoxic compounds

A number of 1,3-bis(benzylidene)-3,4-dihydro-1H-naphthalen-2-ones, 2,6-bis(benzylidene)cyclohexanones, and 3,5-bis(benzylidene)-4-piperidones possess significant potencies toward L1210, Molt 4/C8, and CEM cell lines. The objective of the current 3D QSAR study is to discover some of the structural parameters which govern cytotoxic potencies. The CoMFA models with steric and electrostatic fields provided satisfactory statistical data [(r2cv = 0.485, r2ncv = 0.834, r2pred = 0.591), (r2cv = 0.532, r2ncv = 0.850, r2pred = 0.729), and (r2cv = 0.561, r2ncv = 0.864, r2pred = 0.666)] in regard to the cytotoxic potencies observed toward L1210, Molt 4/C8, and CEM cell lines, respectively. The CoMSIA model with steric, electrostatic, hydrophobic, and H-bond donor fields exhibited r2cv = 0.513, r2ncv = 0.833, and r2pred = 0.562 for cytotoxic activity toward L1210 cells, while the best CoMSIA models were obtained by a combination of steric, electrostatic, and hydrophobic fields which yielded statistically significant data [(r2cv = 0.531, r2ncv = 0.828, r2pred = 0.652) and (r2cv = 0.560, r2ncv = 0.841, r2pred = 0.729)] to explain the cytotoxicity toward Molt 4/C8 and CEM cells, respectively. The information obtained from the CoMFA and CoMSIA 3D contour maps can be used in the design of more potent cytotoxins.     

Synthesis and Crystal Structure of（2E,6E）-2,6-bis（2,3-dimethoxybenzylidene）cyclohexanone

The new title compound (2E,6E)-2,6-bis(2,3-dimethoxybenzylidene)cyclohexanone (C 24 H 26 O 5,M r=394.45) has been synthesized,and its crystal structure was studied.The title compound crystallizes in the orthorhombic system,space group Pca2 1 with a=17.536(2),b=14.8515(16),c=8.0512(9),V=2096.8(4) 3,Z=4,D c=1.250 g/cm 3,λ=0.71073,μ=0.087 mm-1 and F(000)=840.The structure was solved by direct methods and refined to R=0.0533 and wR=0.1248 from 2727 observed reflections (I > 2σ(Ⅰ)).The title molecules are connected through hydrogen bonds to generate a 3-D supramolecule.The preliminary biological tests showed definitely biological activity for the title compound.     

Nanometer Channels and Cages within the Extended Basic Mercurous Cations [(Hg2)3(OH)2]4+ and [(Hg2)2O]2+

The two‐ and three‐dimensional mercurous cations [(Hg₂)₃(OH)₂]⁴⁺ and [(Hg₂)₂O]²⁺ crystallize with channels and cages of roughly 1 nm diameter from aqueous solutions dependent upon the acidity of the solution. Crystal structures were determined, for example, for [Zn(H₂O)₆][(Hg₂)₃(OH)₂](NO₃)₆ (trigonal, space group P321, a = 1183.5(2) pm, c = 534.8(1) pm, Z = 1, R1 = 0.0351 for I₀ > 2σ(I₀)) and for [(Hg₂)₂O][Pb(NO₃)₃]₂ (cubic, space group , a = 1543.1(2) pm, Z = 8, R1 = 0.0534 I₀ > 2σ(I₀)).     

Synthesis, spectroscopic characterizations and quantum chemical computational studies of (Z)-4-[(E)-(4-fluorophenyl)diazenyl]-6-[(3-hydroxypropylamino)methylene]-2-methoxycyclohexa-2,4-dienone

In this study, the molecular structure and spectroscopic properties of the title compound were characterized by X-ray diffraction, FT-IR and UV-vis spectroscopies. These properties were also investigated using DFT method. The most convenient conformation of title compound was firstly determined. The geometry optimizations in gas phase and solvent media were performed by DFT methods with B3LYP adding 6-31G(d) basis set. The differences between crystal and computational structures are due to crystal packing in which hydrogen bonds play an important role. UV-vis spectra were recorded in different organic solvents. The results show that title compound exists in both keto and enol forms in DMSO, EtOH but it tends to shift towards enol form in benzene. The polar solvents facilitate the proton transfer by decreasing the activation energy needed for Transition State. The formation of both keto and enol forms in DMSO and EtOH is due to decrease in the activation energy. TD-DFT calculations starting from optimized geometry were carried out in both gas and solution phases to calculate excitation energies of the title compound. The non-linear optical properties were computed at the theory level and the title compound showed a good second order non-linear optical property. In addition, thermodynamic properties were obtained in the range of 100-500K.     

The base-promoted dehydration of rac.-trans-tetrahydro-6-hydroxy-4-[(2-(dimethylamino)ethyl]-7-(4-methoxyphenyl)-1,4-thiazepin-5(2H)-one

The base-catalyzed alkylation of rac.-trans-tetrahydro-6-hydroxy-7-(4-methoxyphenyl)-1,4-thiazepin-5(2H)-one ( 1 ) with dimethylaminoethyl chloride in dimethyl sulfoxide provided predominantly rac.-trans-tetrahydro-6-hydroxy-4-[(2-dimethylamino)ethyl]-7-(4-methoxyphenyl)-1,4-thiazepin-5(2H)-one ( 2 ) and in addition, 2,3-dihydro-4-[2-(dimethylamino)-ethyl]-7-(4-methoxyphenyl)-1,4-thiazepin-5(4H)-one ( 3 ). A plausible mechanism is postulated for the dehydration of the rac.-trans-amide 2 .     

Photochromism of fulgides and stereoelectronic factors: Synthesis of (E)-4(3)-adamantyhdene-(5)-dicyanomethylene-3(4)-[1-(2,5-dimethylfuryl)ethylidene]tetrahydrofuran-2-one 4 and 4a and (E)-4-adamantylidene-3-[2,6-dimethyl-3,5-bis(p-diethyl-aminostyryl)benzylidene]tetrahydrofuran-2,5-dione 10

In the search for fulgides with potential semiconductor laser compatibility, 4-adamantylidene-5-dicyanomemylene-3-[1-(2,5-dimethyl-3-furyl)ethylidene]tetrahydrofuran-2-one ( 4 ), along with its regioisomer 4a , have been synthesized from the corresponding fulgide 6 containing a succinic anhydride ring by reaction with malononitrile in the presence of diethylamine. Upon irradiation with a uv light at λ_max 350 run, a mixture of 4 and 4a revealed a considerably enhanced bathochromic shift to the visible region, λ_max 605 nm as compared with the starting fulgide 6 which, upon analogous uv irradiation, absorbed at λ_max 515 nm. In the search for semiconductor-laser-compatible fulgides with increased efficiency for the reverse bleaching reaction, another fulgide (E)–adamantylidene-3-[2,6-dimethyl-3,5-bis(p-diethylaminostyryl)-benzylidene]tetrahydrofuran-2,5-dione ( 10 ) was synthesized in seven steps starting from 2-bromo-m-xylene. However, 10 failed to undergo electrocyclic ring-closure upon irradiation with a uv light at λ_max 350 nm. The analogous fulgide 8 , which contains an isopropylidene functionality in place of the adamantyl group of 10 , was resynthesized for comparison, and showed two absorption maxima, one at 545 nm and the other at 620 nm. The missing physico-chemical data for 8 have also been provided.     

Molecular and computational structure characterizations of (E)-2-ethoxy-6-[(4-fluorophenylimino)methyl]phenol

The (E)-2-ethoxy-6-[(4-fluorophenylimino)methyl]phenol compound was synthesized and characterized by X-ray Diffraction, IR and Electronic spectroscopy. X-Ray and IR results showed that the title compound preferred the enol form in solid state. UV-Vis absorption spectra of the title compound were recorded in different solvents. The results showed that the molecule existed only in enol form even in the solvent media. Electronic structure and spectroscopic properties of the title compound were investigated from calculative point of view. The gas phase geometry optimization was obtained based on X-ray geometry by DFT method with B3LYP applying 6-311G(d,p) basis set. Geometry optimizations in the solvent media were obtained with the same level of theory by the polarizable continuum model (PCM). TD-DFT calculations starting from the optimized geometry were made in both gas and solution phase to measure the excitation energies of enol and keto tautomers. Vibrational frequency and natural bond orbital analysis (NBO) were performed and the thermodynamic properties of the title compound were obtained at the optimized geometry with the same level of theory.     

新型1-(4-取代苯基)-3-[4-(4-氧香豆素基)苯基]硫脲衍生物的合成及其抑菌活性

以4-羟基香豆素为原料,经氯化、醚化和异硫氰酸化3步反应制得中间体——4-(4-异硫氰酸酯苯氧基)香豆素(3);3与取代芳香胺经加成反应合成了9个新型的1-(4-取代苯基)-3-[4-(4-氧香豆素基)苯基]硫脲衍生物(4a~4i),其结构经1H NMR,13C NMR,IR和MS(ESI)表征。采用浑浊度法测试了4的抑菌活性。结果表明:4a、4b、4e和4f抑制烟草青枯菌活性EC50值分别为112.02、121.39、88.72和86.90μg·mL~(-1),优于噻菌铜(130.25μg·mL~(-1));4a、4b、4e和4f抑制番茄青枯菌活性EC50值分别为107.89、110.69、82.43和82.48μg·mL~(-1),优于噻菌铜(123.94μg·mL~(-1))。     

IR, MS studies on (+/-)-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine dihydrochloride salt

The vibration spectrum and FAB mass spectrum of (+/-)-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine dihydrochloride salt was studied. By comparing with the spectra of free base, different bands of IR were found in the NH+ stretching, the NH+ deformation motion, the CH2 of NCH2 group symmetric stretching, the CH2 of N-CH2 group twisting and the CN stretching. FAB shows the basic peak is M + H. Other m/e peaks are consistent with the structure.     

2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4- 噻唑啉酮的合成

以2-氨基-5-取代苯氧甲基-1,3,4-噻二唑(1)为起始原料, 合成了中间体2-氯乙酰氨基-5-取代苯氧甲基-1,3,4-噻二唑)-2-乙酰亚胺(2)和2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-4-噻唑啉酮(3), 化合物3进一步与取代苯甲醛发生类Knoevenagle缩合反应, 得到了一系列2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4-噻唑啉酮类化合物4a～4p. 目标化合物4a～4p的结构经IR, ¹H NMR和元素分析确证.     

Reactions of 1,1-bis(dimethylamino)-1,3-butadiene with olefins – (4 + 2) cycloadditions and zwitterion formation

1,1-Bis(dimethylamino)-1,3-butadiene ( 1 ) as a strong donor diene (E_1/2 = 0.03 V vs. SCE, 1st IP_v = 6.94 eV) is treated with acrylonitrile, dimethyl dicyanofumarate, and tetracyanoethylene. Cycloaddition with acrylonitrile is slow and requires elevated temperatures at which elimination of dimethylamine with formation of 1-cyano-2-(dimethylamino)-1,3-cyclohexadiene occurs. The reaction of 1 with TCNE at −40°C in acetonitrile is very fast and leads to the zwitterion 5 . At T ⩾ −20°C, 5 eliminates hydrogen cyanide to give a highly colored (λ_max = 489 nm, lgϵ = 4.716) merocyanine. A zwitterion 9 generated from 1 and dimethyl dicyanofumarate can be isolated in crystalline form. The structural analysis shows that the zwitterions are produced by attack of the olefin at the antiperiplanar conformation of 1 . Both zwitterions which can be trapped as crystalline picrates cannot be converted to cycloadducts. These results suggest that cycloaddition is observed if zwitterion formation becomes energetically unfavorable.     

Synthesis of (2E)-2-(tetrafluoroethylidene)-3,3-bis(trifluoromethyl)-2,3-dihydrothiazolo[3,2-a]benzimidazole

The reaction of benzimidazoline-2-thione with perfluoro-2-methylpent-2-ene in the presence of triethylamine afforded (2E)-2-(tetrafluoroethylidene)-3,3-bis(trifluoromethyl)-2,3-dihydrothiazolo[3,2-a]benzimidazole whose structure was confirmed by X-ray diffraction analysis. The reaction pathways are discussed.     

Crystal structure, spectroscopy, and quantum chemical studies of (E)-2-[(2-chlorophenyl)iminomethyl]-4-trifluoromethoxyphenol

The Schiff base compound (E)-2-[(2-chlorophenyl)iminomethyl]-4-trifluoromethoxyphenol has been synthesized and characterized by IR, UV-vis, and X-ray single-crystal determination. The molecular geometry from X-ray experiment in the ground state has been compared using the density functional theory (DFT) with the 6-311++G(d,p) basis set. The calculated results show that the DFT can well reproduce the structure of the title compound. Using the TD-DFT method, electronic absorption spectra of the title compound have been predicted, and a good agreement is determined with the experimental ones. To investigate the tautomeric stability, optimization calculations at the B3LYP/6-311++G(d,p) level were performed for the enol and keto forms of the title compound. Calculated results reveal that its enol form is more stable than its keto form. The predicted nonlinear optical properties of the title compound are much greater than those of urea. The changes of thermodynamic properties for the formation of the title compound with the temperature ranging from 200 to 500 K have been obtained using the statistical thermodynamic method. At 298.15 K, the change of Gibbs free energy for the formation reaction of the title compound is -824.841 kJ/mol. The title compound can spontaneously be produced from the isolated monomers at room temperature. The tautomeric equilibrium constant is also computed as 3.85 × 10(-4) at 298.15 K for enol?keto tautomerization of the title compound. In addition, a molecular electrostatic potential map of the title compound was performed using the B3LYP/6-311++G(d,p) method.     

有机电致红光材料 4-(二腈亚甲叉)-2-甲基-6-(4-二甲胺基-苯乙烯)-4H-吡喃的合成新方法

设计全新的路线合成了红光材料4-(二腈亚甲叉)-2-甲基-6-(4-二甲胺基-苯乙烯)-4H-吡喃(DCM)。采用具有烯烃骨架的β-苯基丙烯酸酯为中间体先引入双键,再经过三酮合环制备乙烯基吡喃。     

2,5-di-[2-(3,5-bis(2-pyridylmethyl)amine -4-hydroxy-phenyl) ethylene] pyrazine zinc complex as fluorescent probe for labeling proteins

The binding characteristics between 2,5-di-[2-(3,5-bis(2-pyridylmethyl)amine -4-hydroxy-phenyl) ethylene] pyrazine (1) or its complex (1-Zn) and serum albumins were studied by fluorescence spectroscopy in pH 7.4 aqueous solution. 1-Zn emitted weak fluorescence at 580 nm in a pH 7.4 Tris-HCl buffer solution when excited at 435 nm, however, the fluorescence intensity increased upon addition of serum albumins with the blue shift of emission peak to 524 nm. The binding constants were estimated as 8.40 x 10(7) and 3.03 x 10(6)mol(-1)L for bovine serum albumin (BSA) and human serum albumin (HSA) respectively, and the number of binding sites was 1 for each. The quenching mechanism of fluorescence of serum albumins by 1-Zn was considered as a static quenching process. The binding distance between 1-Zn and serum albumins and the energy transfer efficiency were obtained based on the theory of F?rester spectroscopy energy transfer. The effect of 1-Zn on the conformation of serum albumins was further analyzed using synchronous fluorescence spectrometry. The experiment results clearly showed that 1-Zn is a highly sensitive protein sensor.     

5-甲氧基-2-[(E)-(6-甲基吡啶-2-亚氨基)甲基]苯酚的合成与表征

研究了以2-羟基-4-甲氧基苯甲醛和2-氨基-6-甲基吡啶为原料合成新型席夫碱化合物5-甲氧基-2-[(E)-(6-甲基吡啶-2-亚氨基)甲基]苯酚的方法。当2-羟基-4-甲氧基苯甲醛与2-氨基-6-甲基吡啶摩尔比为1∶1.6,反应时间为6 h,反应温度为75℃时,反应产率最高。采用元素分析、UV-Vis、IR、1H NMR、X-射线单晶衍射等方法进行结构表征。该化合物为单斜晶系,空间群P21/c,a=1.1886(3)nm,b=0.65948(16)nm,c=1.6897(4)nm,β=108.505(3)°,V=1.2560(5)nm3,Dc=1.281 g·cm-3,Z=4,F(000)=512,μ=0.087 mm-1,R1=0.0477,wR2=0.1342。通过π···π堆积和分子内氢键O2-H2···N1、C8-H8A···N2形成较稳定的晶体结构,并具有蓝色荧光。     

Molecular modeling and spectroscopic studies on binding of 2,6-bis[4-(4-amino-2-trifluoromethylphenoxy)benzoyl] pyridine to human serum albumin

BAFP (2,6-bis[4-(4-amino-2-trifluoromethylphenoxy)benzoyl] pyridine), a synthesized polyimide compound, was exploited for the first time to analyze its interaction with human serum albumin (HSA) by molecular modeling, fluorescence and Fourier transform infrared attenuated total reflection spectroscopy (FTIR ATR) with drug concentrations of 3.3 × 10⁻⁶ to 3.0 × 10⁻⁵ mol L⁻¹. Molecular docking was performed to reveal the possible binding mode. The results suggested that BAFP can strongly bind to human serum albumin (HSA) and the primary binding site of BAFP is located in site II of HSA, which is supported by the results from the competitive experiment. The binding constants for the interaction of BAFP with HSA have been evaluated from relevant fluorescence data at different temperatures (296, 303, 310 and 308 K). The alterations of the protein secondary structure in the presence of BAFP in aqueous solution were quantitatively calculated by the evidences from FTIR ATR spectroscopes. The binding process was exothermic and spontaneous, as indicated by the thermodynamic analyses, and the major part of the binding energy is hydrophobic interaction, which is also in good agreement with the results of molecule modeling study. The enthalpy change ΔH⁰, the free energy change ΔG⁰ and the entropy change ΔS⁰ of 296 K were calculated to be −7.75, −27.68 kJ mol⁻¹ and 67.33 J mol⁻¹ K⁻¹, respectively.     

The unexpected formation of a lithium-enolate from bis2-[(dimethylamino)methyl]phenyl copper lithium. X-ray structure of Li4[OC(CH2)C6H4CH2NMe2-2]4

Attempted crystallization of the bis(aryl)lithium cuprate, Cu₂Li₂(C₆H₄CH₂-NMe₂-2)₄, from diethyl ether/pentane afforded in according to an X-ray diffraction analysis appeared to be the lithium enolate, Li₄[OC(=CH₂)C₆H₄CH₂NMe₂-2]₄. This consists of a central Li₄O₄ cube with intramolecular LiN coordination of the CH₂NMe₂ substituent. This enolate, which has also been prepared via an independent route, is the first example of a structurally characterized lithium enolate and contains Li centres that are intramolecularly coordinated.     

Synthesis and molecular docking studies of novel 2-phenyl-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]benzylidene}oxazol-5(4H)-one derivatives

Russian Journal of General Chemistry - 2-Phenyl-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]benzylidene}oxazol-5(4H)-one derivatives were synthesized by click chemistry reactions. Exploration of...