Microtubule Destabilizing Sulfonamides as an Alternative to Taxane-Based Chemotherapy

Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.     

Ab-initio study of electronic and elastic properties of Mg(BH4)(NH2) complex hydride

Structural and electronic properties of complex hydride Mg(BH₄)(NH₂), applicable in hydrogen storage, were studied in framework of pseudopotential-density functional theory. This compound shows an indirect band gap of 4.95 eV which is categorized in insulator materials. The calculated total and partial density of states of this compound show that the hydrogen bonding in BH₄ anion is mainly covalent and the hydrogen-hydrogen repulsion is more in anion BH₄ than in anion NH₂. The calculated bulk modulus from Birch-Murnaghan equation of state is in close agreement with that obtained from the elastic constants. The obtained bulk modulus (19.27 GPa) shows this compound is more ductile than binary and ternary hydrides and it does not have a brittle structure. Therefore, it is a good candidate for hydrogenation and dehydrogenation cycles. The stability of the structure in ambient pressure is also declared by calculating the elastic coefficients. However, the existence of elastic anisotropy in the compound demonstrates the less compressibility of it along the c axis than a and b axes. The small amount of Poisson ratio indicates that it is more stable against shear compared to common borohydrides. This point is important for hydride stability in hydrogenation and dehydrogenation cycles.     

2,2-Dicyanovinyl-end-capped oligothiophenes as electron acceptor in solution processed bulk-heterojunction organic solar cells

Three 2,2-dicyanovinyl (DCV) end-capped A-π-D-π-A type oligothiophenes (DCV-OTs) containing dithieno[3,2-b:2′,3′-d]silole (DTSi), cyclopenta[1,2-b:3,4-b′]dithiophene (DTCP) or dithieno[3,2-b:2′,3′-d]pyrrole (DTPy) unit as the central donor part, mono-thiophene as the π-conjugation bridge were synthesized. The absorption spectroscopies, cyclic voltammetry of these compounds were characterized. Results showed that all these compounds have intensive absorption band over 500–680 nm with a LUMO energy level around −3.80 eV, which is slightly higher than that of [6,6]phenyl-C₆₁-butyric acid methyl ester (PC₆₁BM, E_LUMO = −4.01 eV), but lower than that of poly(3-hexylthiophene) (P3HT, E_LUMO = −2.91 eV). Solution processed bulk heterojunction “all-thiophene” solar cells using P3HT as electron donor and the above mentioned oligothiophenes as electron acceptor were fabricated and tested. The highest power conversion efficiency (PCE) of 1.31% was achieved for DTSi-cored compound DTSi(THDCV)₂, whereas PTB7:DTSi(THDCV)₂ based device showed slightly higher PCE of 1.56%. Electron mobilities of these three compounds were measured to be around 10⁻⁵ cm² V⁻¹ s⁻¹ by space charge limited current method, which is much lower than that of PC₆₁BM, and was considered as one of the reason for the low photovoltaic performance.     

An autothermal reforming system for diesel and jet fuel with quick start-up capability

A quick, low energy consuming and reliable start-up is essential for fuel cell systems utilizing diesel and jet fuel. A compact fuel processor for coupling with a high-temperature polymer electrolyte fuel cell is developed with electrically-heated reactors in the 28 kW_th power class. Based on this set-up, start-up strategies are developed and validated. With the basic strategy, 14 min are required in the best case to commence reforming and achieve self-sustaining operation with desired CO concentration at full load using NExBTL diesel and, respectively, 16 min using Jet A-1. However, using premium diesel, the basic strategy leads to a strong increase in the concentrations of ethane and benzene. An advanced strategy enables 16 min start time with premium diesel suppressing these undesired side products. This result is within the 30 min start-up time target for auxiliary power units for 2020 and offers a reliable option for real world applications.     

Supercooling of water droplets in jet aviation fuel

Ice formation in aircraft fuel systems is an ongoing problem with potentially disastrous consequences. Unfortunately, the icing of fuel systems is poorly understood. It is well known that at temperatures below 0 °C particles of H₂O suspended in fuel can exist as crystalline ice or metastable supercooled water. In this paper we show that micron sized water droplets immersed in Jet A-1 aviation fuel can exist in a metastable supercooled state to around −36 °C. In fact, the majority of droplets in our experiments froze homogeneously showing that the fuel itself did not catalyse ice formation. We suggest that H₂O particles will remain in a supercooled liquid state until they come into contact with a suitable solid surface in an aircraft’s fuel system or the temperature falls below the homogeneous freezing limit.     

高温下火电机组常用金属材料的纯十八胺成膜特性研究

采用GCF型高压釜模拟高于350℃下的水汽环境,对20G、T22、SA210A-1等3种火电机组水汽系统常用材质进行了十八胺成膜试验,依据硫酸铜点滴试验、交流阻抗、极化曲线等方法评价成膜效果,并利用Matlab 6.5对结果进行回归分析.结果表明:在温度为470～490℃,十八胺浓度为60～70mg/L,恒温时间为3～5 h,pH值为8.8左右时,3种金属材料表面均能形成很好的保护膜,其中pH值对成膜效果影响最大,最佳pH值为9.0.此外,十八胺在不同金属表面成膜效果存在差异.     

80A-51泥浆在钻井生产中的应用

介绍了80A—51泥浆的作用机理及在钻井生产中的应用效果。     

500kV变压器直流偏磁下的铁心损耗分析研究

为了研究变压器直流偏磁下的铁心损耗,文章以某一核电站500 k V主变压器为例,在二维有限元瞬态场A–φ算法基础下构造了直流偏磁下的变压器二维仿真损耗模型。在仿真中,偏磁直流量从0 A增加至30 A,可得到变压器铁心的损耗分布。结果分析可表明:随着偏磁直流量的增加,励磁电流会产生畸变和较大的偶次谐波,并导致铁心局部损耗增大,其中:铁心主柱与上、下铁轭交接区域的损耗值受到直流偏磁的影响最大,铁心水平路径的损耗值相较于垂直路径受直流偏磁的影响较大。     

151Eu Mössbauer studies on Zn-doped EuBa2Cu3O7−y

¹⁵¹Eu Mössbauer studies have been performed on the compounds EuBa₂(Cu_1?x Zn _x )₃O_7?y withx=0·0, 0·025, 0·05, 0·075 and 0·1. The parent compound, EuBa₂Cu₃O_7?y is superconducting with a transition temperature (T _c ) of 88 K.T _c is depressed as Zn is substituted for Cu in this system and the compounds withx>0·05 do not show superconductivity down to 12 K.¹⁵¹Eu Mössbauer studies at 295 K show a single Mössbauer line in all the compounds (whether superconducting or not) with isomer shift value typical of Eu^{3 +} ion. Further, the isomer shift values are nearly independent ofx and the temperatures down to 10 K. These observations imply that the Cu-O network responsible for superconductivity is very weakly coupled to the Eu sublattice.     

Surface activity of the lipid products hydrolyzed with lipase and phospholipase A-2

We examined thein vitro surface activity, immersional wettability and adhesional wettability shown by aqueous solutions of soy lysophospholipid (SLP)/monoglyceride (MG)/fatty acid (FA), SLP/FA and SLP/MG, and found that many lipid mixtures showed significant surface activity when their MG and FA components consisted of polyunsaturated FA and/or medium chain FA. The more unsaturated the FA, the higher the surface activity. A mixture of SLP/medium chain fatty acid MG (medium chain MG)/medium chain FA showed the highest surface activity, and was comparable to an Aerosol-OT surfactant, the most effective wetting agent. SLP/polyunsaturated FA monoglyceride (polyunsaturated MG)/polyunsaturated FA, SLP/medium chain FA, and SLP/polyunsaturated FA, SLP/medium chain MG, and SLP/polyunsaturated MG also showed a high degree of activity. Wettability decreased rapidly when the amount of saturated, long chain FA moieties increased. It is recognized that the degrees of unsaturation and the chain length of FAs in the lipid mixtures have a decisive influence on surface activities. Higher ratios of MG and FA to SLP gave higher activity; and solubilizers such as bile salts were necessary to dissolve them in water.