Exploring Ovarian Cancer Cell Resistance to Rhenium Anticancer Complexes

Rhenium tricarbonyl complexes have been recently investigated as novel anticancer agents. However, little is understood about their mechanisms of action, as well as the means by which cancer cells respond to chronic exposure to these compounds. To gain a deeper mechanistic insight into these rhenium anticancer agents, we developed and characterized an ovarian cancer cell line that is resistant to a previously studied compound [Re(CO)₃(dmphen)(ptolICN)]⁺, where dmphen=2,9‐dimethyl‐1,10‐phenanthroline and ptolICN=para‐tolyl isonitrile, called TRIP. This TRIP‐resistant ovarian cancer cell line, A2780TR, was found to be 9 times less sensitive to TRIP compared to the wild‐type A2780 ovarian cancer cell line. Furthermore, the cytotoxicities of established drugs and other rhenium anticancer agents in the TRIP‐resistant cell line were determined. Notably, the drug taxol was found to exhibit a 184‐fold decrease in activity in the A2780TR cell line, suggesting that mechanisms of resistance towards TRIP and this drug are similar. Accordingly, expression levels of the ATP‐binding cassette transporter P‐glycoprotein, an efflux transporter known to detoxify taxol, were found to be elevated in the A2780TR cell line. Additionally, a gene expression analysis using the National Cancer Institute 60 cell line panel identified the MT1E gene to be overexpressed in cells that are less sensitive to TRIP. Because this gene encodes for metallothioneins, this result suggests that detoxification by this class of proteins is another mechanism for resistance to TRIP. The importance of this gene in the A2780TR cell line was assessed, confirming that its expression is elevated in this cell line as well. As the first study to investigate and identify the cancer cell resistance pathways in response to a rhenium complex, this report highlights important similarities and differences in the resistance responses of ovarian cancer cells to TRIP and conventional drugs.     

过渡金属掺杂铈中晶格氧的活化

采用密度泛函理论计算研究了在铈表面掺杂的过渡金属(TM)离子对表面晶格氧原子活化的影响.为此,测定了经TM离子修饰的CeO2最稳定(111)表面终端的结构和稳定性.除了保持八面体氧配位的锆和铂掺杂剂外, TM掺杂剂在取代表面Ce离子时更倾向于正方形平面配位.除了Pt(1.14 eV)和Zr(正方形平面配位不稳定)外,所有TM掺杂剂的表面结构从八面体到正方形平面都很容易.通常,四价TM阳离子的离子半径比Ce^4+的小得多,从而导致了显著的拉伸应变晶格,并解释了氧空位形成能量的降低.除Zr外,当产生一个氧空位时,优先形成正方形平面结构.热力学分析表明, TM掺杂CeO2表面在典型环境催化条件下存在氧缺陷.一个具有实际意义的例子是锆掺杂CeO2(111)中的晶格氧容易活化,从而有利于CO氧化.研究结果强调了晶格氧活化的本质和TM掺杂剂在TM-铈固溶催化剂中的优选位置.     

Enhanced Photocatalytic Hydrogen Production by Hybrid Streptavidin-Diiron Catalysts

Hybrid protein–organometallic catalysts are being explored for selective catalysis of a number of reactions, because they utilize the complementary strengths of proteins and of organometallic complex. Herein, we present an artificial hydrogenase, StrepH2, built by incorporating a biotinylated [Fe–Fe] hydrogenase organometallic mimic within streptavidin. This strategy takes advantage of the remarkable strength and specificity of biotin-streptavidin recognition, which drives quantitative incorporation of the biotinylated diironhexacarbonyl center into streptavidin, as confirmed by UV/Vis spectroscopy and X-ray crystallography. FTIR spectra of StrepH2 show characteristic peaks at shift values indicative of interactions between the catalyst and the protein scaffold. StrepH2 catalyzes proton reduction to hydrogen in aqueous media during photo- and electrocatalysis. Under photocatalytic conditions, the protein-embedded catalyst shows enhanced efficiency and prolonged activity compared to the isolated catalyst. Transient absorption spectroscopy data suggest a mechanism for the observed increase in activity underpinned by an observed longer lifetime for the catalytic species Fe^IFe⁰ when incorporated within streptavidin compared to the biotinylated catalyst in solution.     

The Geometric Approach for Constructing Sinai–Ruelle–Bowen Measures

An important class of ‘physically relevant’ measures for dynamical systems with hyperbolic behavior is given by Sinai–Ruelle–Bowen (SRB) measures. We survey various techniques for constructing SRB measures and studying their properties, paying special attention to the geometric ‘push-forward’ approach. After describing this approach in the uniformly hyperbolic setting, we review recent work that extends it to non-uniformly hyperbolic systems.     

Renormalization of scalar quartic and Yukawa couplings in unified gauge theories based onE 6

Renormalization group equations for scalar and Yukawa couplings in gauge theories based on the exceptional groupE ₆ are analyzed. Asymptotic freedom is possible only for a limited set of scalar fields, and then only if several fermion generations are present. The infrared behavior of the scalar quartic coupling constants is striking: they are necessarily driven out of the region of positivity of the classical potential. Some useful group theoretic relations inE ₆ are given in an Appendix.     

Intramolecular chiral relay at stereogenic nitrogen. Synthesis and application of a new chiral auxiliary derived from (1R,2S)-norephedrine and acetone

(1R,2S)-Norephedrine has been employed in the synthesis of a novel 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one via reductive alkylation with acetone, N-nitrosation, reduction, and cyclization. The oxadiazinone was treated with either propionyl chloride or 3-thiophenylpropionyl chloride to afford the corresponding N(3)-acylated oxadiazinones 9a and 9b, respectively. X-ray crystallographic analysis of the N(3)-thiophenylpropionyl oxadiazinone 9b revealed that the C(2)-urethane carbonyl and the N(3)-carbonyl are arranged in an anti-periplanar conformation. The oxadiazinones were subsequently applied in the titanium-mediated asymmetric aldol addition reaction by treatment with titanium tetrachloride, triethylamine, and a variety of aldehydes at 0 degrees C. The aldol adducts 10a-i and 11a,b were found to have diastereoselectivities ranging from 8:1 to >99:1 favoring the formation of the non-Evans syn configuration. The absolute stereochemistry of the adduct 10a was determined by acid hydrolysis. This process afforded the N(4)-isopropyloxadiazinone 8 and (2S,3S)-3-hydroxy-2-methyl-3-phenylpropanoic acid 14 in >/=95% enantiomeric excess.     

Quark loop model of radiative meson decays

Radiative meson decays are computed from quark loop anomalies, taking into account the SU(3) splitting of the quark masses. Predicted rates for ?→ηγ,K ^*→Kγ, and η→ππγ are brought into satisfactory agreement with experiment. Formulas are given for the radiative decay rates of charmed las are given for the radiative decay rates of charmed mesons, and a mechanism suggested for suppression of the radiative decays of mesons containing a charmed quark.     

薄壁杆系结构的梁元分析模型

本文导出了用于薄壁杆系结构弹性分析的薄壁梁元分析模型，在空间梁元分析模型^[3]的基础上，采用了一种改进的位移模式，考察了薄壁杆件可能发生的拉压，剪切，弯曲，扭转和翘曲等各变形形式以及它们的耦合效应，得出了相应的单元形函数，同时从工程应变的定义出发，采用Taylor级数展开的方法，建立了单元的五阶近似正交变表达式，并建立了相应的薄壁单元刚度方程，从而得出了局部坐标系下单元刚度矩阵的显式，根据本文所导出的薄壁梁元分析模型，编制了相应的结构计算程序，通过算例验证了本文所推导的单元刚度矩阵，同时通过与传统空间梁元计算模型计算结果的比较，阐述了截面翘曲对薄壁杆系结构的影响。