Design,Synthesis and Biological Evaluation of Novel and Potent Protein Arginine Methyltransferases 5 Inhibitors for Cancer Therapy

Protein arginine methyltransferases 5 (PRMT5) is a clinically promising epigenetic target that is upregulated in a variety of tumors. Currently, there are several PRMT5 inhibitors under preclinical or clinical development, however the established clinical inhibitors show favorable toxicity. Thus, it remains an unmet need to discover novel and structurally diverse PRMT5 inhibitors with characterized therapeutic utility. Herein, a series of tetrahydroisoquinoline (THIQ) derivatives were designed and synthesized as PRMT5 inhibitors using GSK-3326595 as the lead compound. Among them, compound 20 (IC₅₀: 4.2 nM) exhibits more potent PRMT5 inhibitory activity than GSK-3326595 (IC₅₀: 9.2 nM). In addition, compound 20 shows high anti-proliferative effects on MV-4-11 and MDA-MB-468 tumor cells and low cytotoxicity on AML-12 hepatocytes. Furthermore, compound 20 possesses acceptable pharmacokinetic profiles and displays considerable in vivo antitumor efficacy in a MV-4-11 xenograft model. Taken together, compound 20 is an antitumor compound worthy of further study.     

碱性去活性柱液相色谱测定水溶性维生素

采用碱性去活性柱高效液相色谱法同时分离测定了７种水溶性维生素。不需加入离子对试剂和胺类改性剂,峰形尖锐,用梯度洗脱分离完全,效果良了,方法的精密度为标准偏差５％以内,回收率为８９％￣１０２％,并用于实际样品的测定。     

The Luminescence of The Phosphor Sr_2ZrO_4 with One-dimensional Chains Structure

IntroductionThenumberofzirconateswhichcanbeexcitedbyconventionalUVexcitation(X>240urn)issmall,sothatzirconateemissioniseasilyoverlooked.SomecompoundswhichabsorbcoventionalUVradiation.ig.ZrO,andBaZrO,(240urn)donotluminenceowingtoenergymigration=.Ontheotherhand,althoughseveralzircinatessuchasZrP,O,:.BaZrSi,O,'andSrZrSi=O,'showefficientUVzirconateemission(around300"m),theirexcitationwavelengthsareshorterthanusual(200"m).Moreover.theirluminescenceareatverylowtemperature(4.2K),whichlimits…     

Orbital deletion procedure and its applications

The orbital deletion procedure is introduced, which is suited to quantitatively investigating the electronic delocalization effiect in earboeations and boranes. While the routine, ab initio molecular orbital methods can generate wavefunetions for real systems where all electrons are delocalized, the present orbital deletion procedure can generate wavefunctions for hypothetical reference molecules where electronic delocalization effect is deactivated. The latter wavefunetion normlly corresponds In the most stable resonance structure in terms of the resonance theory. By comparing and analyzing the delocalized and the localized wavefunetions, one can obtain a quantitative and instinct pieture to show how electronic deloealizalion inside a molecule affects the molecular structure, energy as well as other physical properties. Two examples are detailedly discussed. The first is related to the hypercoujugation of alkyl groups in carbocations and a comparison of the order of stability of carbocations is made, T     

PLD-assisted VLS growth of aligned ferrite nanorods, nanowires, and nanobelts-synthesis, and properties

We report here a systematic synthesis and characterization of aligned alpha-Fe2O3 (hematite), epsilon-Fe2O3, and Fe3O4 (magnetite) nanorods, nanobelts, and nanowires on alumina substrates using a pulsed laser deposition (PLD) method. The presence of spherical gold catalyst particles at the tips of the nanostructures indicates selective growth via the vapor-liquid-solid (VLS) mechanism. Through a series of experiments, we have produced a primitive "phase diagram" for growing these structures based on several designed pressure and temperature parameters. Transmission electron microscopy (TEM) analysis has shown that the rods, wires, and belts are single-crystalline and grow along <111>m or <110>h directions. X-ray diffraction (XRD) measurements confirm phase and structural analysis. Superconducting quantum interference device (SQUID) measurements show that the iron oxide structures exhibit interesting magnetic behavior, particularly at room temperature. This work is the first known report of magnetite 1D nanostructure growth via the vapor-liquid-solid (VLS) mechanism without using a template, as well as the first known synthesis of long epsilon-Fe2O3 nanobelts and nanowires.     

担载型铱催化剂上CO吸附量热和红外光谱研究

分别对Al2O3和SiO2担载的不同含量铱(Ir)催化剂进行了H2程序升温还原、CO微量吸附量热和红外研究.结果表明,还原后,Ir/Al2O3上存在金属态Ir0和氧化态Irδ 两种物种,CO在催化剂表面主要以线式和孪生吸附态存在,测量的CO吸附热为两种吸附形式的平均吸附热.提高还原温度和Ir担载量,Ir/Al2O3表面CO线式吸附物种的比例增加,从而导致CO吸附热值的升高.而在Ir/SiO2上Ir物种主要为金属态Ir0,CO吸附都以线式吸附为主,在所考察的条件下CO吸附热随Ir担载量和还原温度的变化不明显。     

The anharmonic effect study of coupled Morse oscillators for the unimolecular reaction

The importance of anharmonic effect in dissociation of molecular systems especially clusters has been noted. In this paper, we shall study the effect of coupled anharmonic oscillator of the standard bilinear form (SBF) Morse oscillator (MO) potential on unimolecular reaction. We shall use the systematic theoretical approach, YL method, proposed by Yao and Lin (YAO L, et. al. J Phys Chem A, 2007, 111(29): 6722-6729), which can evaluate anharmonic effects on the rate constants based on the transition state theory. In treating the anharmonic effect with the Morse oscillator potential on unimolecular reactions under collision-free conditions by using the RRKM (Rice-Ramsperger-Kassel-Marcus) theory, the in-verse Laplace transformation of the partition functions was used to obtain the total amount of state and density of state by using the first-order and the second-order approximations of the saddle-point method. To demonstrate the anharmonic effect of the SBF Morse model, we choose some model systems and a real reaction as examples.     

Syntheses and structures of half-sandwich iridium(III) and rhodium(III) complexes with organochalcogen (S, Se) ligands bearing N-methylimidazole and their use as catalysts for norbornene polymerization

The organochalcogen ligands derived from 3-methyl-imidazole-2-thione/selone groups, Mbit, Mbis, Ebit and Ebis [Mbit = 1,1'-methylenebis(3-methyl-imidazole-2-thione); Mbis = 1,1'-methylenebis(3-methyl-imidazole-2-selone), Ebit = 1,1'-(1,2-ethanediyl)bis(3-methyl-imidazole-2-thione), Ebis = 1,1'-(1,2-ethanediyl)bis(3-methyl-imidazole-2-selone)] have been synthesized and characterized. Reactions of [Cp*Ir(micro-Cl)Cl]2 and [Cp*Rh(micro-Cl)Cl]2 (Cp* = eta5-pentamethylcyclopentadienyl) with Mbit, Mbis, Ebit and Ebis result in the formation of the complexes [Cp*Ir(Mbit)Cl]Cl 1a x Cl), [Cp*Ir(Mbis)Cl]Cl (3a x Cl), [Cp*Ir(Ebit)Cl]Cl (1b x Cl), [Cp*Ir(Ebis)Cl]Cl (2a x Cl), [Cp*Rh(Mbit)Cl]Cl (2b x Cl), Cp*Rh(Mbis)Cl][Cp*RhCl(3)] (3b x[Cp*RhCl(3)]), [Cp*Rh(Ebit)Cl]Cl (4a x Cl) and [Cp*Rh(Ebis)Cl]Cl (4b x Cl), respectively. All compounds have been characterized by elemental analysis, NMR and IR spectra. The molecular structures of 1b, 2b, 3a, 3b and 4a have been determined by X-ray crystallography. After activation with methylaluminoxane (MAO), the iridium complexes exhibit moderate activities for the vinyl polymerization of norbornene.     

DNA tile based self-assembly: building complex nanoarchitectures.

DNA tile based self-assembly provides an attractive route to create nanoarchitectures of programmable patterns. It also offers excellent scaffolds for directed self-assembly of nanometer-scale materials, ranging from nanoparticles to proteins, with potential applications in constructing nanoelectronic/nanophotonic devices and protein/ligand nanoarrays. This Review first summarizes the currently available DNA tile toolboxes and further emphasizes recent developments toward self-assembling DNA nanostructures with increasing complexity. Exciting progress using DNA tiles for directed self-assembly of other nanometer scale components is also discussed.     

A DFT study on the mechanism of hydrosilylation of unsaturated compounds with neutral hydrido(hydrosilylene)tungsten complex

Recently, Tobita et al. reported stoichiometric hydrosilylation reactions of acetone and acetonitrile with neutral hydrido(hydrosilylene)tungsten complexes Cp'(CO)2(H)W=Si(H)[C(SiMe(3))(3)] (Cp' = Cp*, C(5)Me(4)Et). The mechanisms of the hydrosilylation reactions of unsaturated compounds (ketone and nitrile) with the tungsten complexes have been investigated with the B(3)LYP density functional theory method. Four possible reaction mechanisms were studied. The results of the calculations indicate that the hydrosilylation of acetone proceeds via a metal hydride migration mechanism proposed by Tobita et al., while the hydrosilylation of nitrile occurs through a silyl migration mechanism, analogous to the modified Chalk-Harrod mechanism. The [2(sigma)+2(pi)] additions of various CX (CX = C=O or CN) multiple bonds with the Si-H bonds in the neutral complexes have very high barriers although similar additions were found feasible in other related cationic complexes. All the hydrosilylation reactions studied here give stable tungsten-silylene or tungsten-silyl products, which are not easily converted into the starting hydrido(hydrosilylene)tungsten complexes when reacting with a hydrosilane substrate molecule. Therefore, we predict that hydrosilylation of acetonitrile and acetone catalyzed by these tungsten complexes is difficult to achieve.