Discovery of Cell‐Permeable Inhibitors That Target the BRCT Domain of BRCA1 Protein by Using a Small‐Molecule Microarray

BRCTs are phosphoserine‐binding domains found in proteins involved in DNA repair, DNA damage response and cell cycle regulation. BRCA1 is a BRCT domain‐containing, tumor‐suppressing protein expressed in the cells of breast and other human tissues. Mutations in BRCA1 have been found in ca. 50 % of hereditary breast cancers. Cell‐permeable, small‐molecule BRCA1 inhibitors are promising anticancer agents, but are not available currently. Herein, with the assist of microarray‐based platforms, we have discovered the first cell‐permeable protein–protein interaction (PPI) inhibitors against BRCA1. By targeting the (BRCT)₂ domain, we showed compound 15 a and its prodrug 15 b inhibited BRCA1 activities in tumor cells, sensitized these cells to ionizing radiation‐induced apoptosis, and showed synergistic inhibitory effect when used in combination with Olaparib (a small‐molecule inhibitor of poly‐ADP‐ribose polymerase) and Etoposide (a small‐molecule inhibitor of topoisomerase II). Unlike previously reported peptide‐based PPI inhibitors of BRCA1, our compounds are small‐molecule‐like and could be directly administered to tumor cells, thus making them useful for future studies of BRCA1/PARP‐related pathways in DNA damage and repair response, and in cancer therapy.     

An Organotrifluoroborate for Broadly Applicable One‐Step 18F‐Labeling

A new zwitterionic organotrifluoroborate is appended to three radiosynthons that afford undergo facile bioconjugation to several clinically relevant peptides and one enzyme inhibitor. Molecularly complex bioconjugates are ¹⁸F‐labeled in a single aqueous step in rapid time (<15 min) without HPLC purification to afford tracers in good yields (>200 mCi, 20–40 %) at high specific activity (≥3 Ci/μmol) and at >98 % purity. PET imaging shows in vivo stability and tumor uptake.     

Rhodium‐Catalyzed Cyclization of Diynes with Nitrones: A Formal [2+2+5] Approach to Bridged Eight‐Membered Heterocycles

N‐aryl‐substituted nitrones were employed as five‐atom coupling partners in the rhodium‐catalyzed cyclization with diynes. In this reaction, the nitrone moiety served as a directing group for the catalytic C? H activation of the N‐aryl ring. This formal [2+2+5] approach allows rapid access to bridged eight‐membered heterocycles with broad substrate scope. The results of this study may provide new insight into the chemistry of nitrones and find applications in the synthesis of other heterocycles.     

Rhodium(III)‐Catalyzed Transannulation of Cyclopropenes with N‐Phenoxyacetamides through CH Activation

An efficient rhodium(III)‐catalyzed synthesis of 2H‐chromene from N‐phenoxyacetamides and cyclopropenes has been developed. The reaction represents the first example of using cyclopropenes as a three‐carbon unit in rhodium(III)‐catalyzed C(sp²)? H activations.     

Ab Initio Study on the Stability of NgnBe2N2, NgnBe3N2 and NgBeSiN2 Clusters

The global minima of Be₂N₂, Be₃N₂ and BeSiN₂ clusters are identified using a modified stochastic kick methodology. The structure, stability and bonding nature of these clusters bound to noble gas (Ng) atoms are studied at the MP2/def2‐QZVPPD level of theory. Positive Be?Ng bond dissociation energy, which gradually increases down Group 18 from He to Rn, indicates the bound nature of Ng atoms. All of the Ng‐binding processes are exothermic in nature. The Xe and Rn binding to Be₂N₂ and Be₃N₂ clusters and Ar?Rn binding to BeSiN₂ are exergonic processes at room temperature; however, for the lighter Ng atoms, lower temperatures are needed. Natural population analysis, Wiberg bond index computations, electron density analysis, and energy decomposition analysis are performed to better understand the nature of Be?Ng bonds.     

Synthesis,thermal, and photophysical properties of polymethylmethacryalte (PMMA) doped with ternary deuterated Eu(III) complexes

Two Eu(III) ternary luminescent complexes, Eu(tpb-H)₃(Tppo)₂ and Eu(tpb-H)₃(Topo)₂ (Tppo: triphenylphosphine oxide, Topo: trioctylphosphine oxide, tpb: 4,4,4-trifluoro-1-phenyl-1,3-butanedione) were synthesized using β-diketonates and phosphine oxides as ligands. Luminescent polymers were fabricated by incorporating the deuterated Eu(III) complexes in a PMMA matrix. Luminescent PMMA containing Eu(tpb-D)₃(Tppo)₂ exhibited relatively higher quantum yield, faster radiation rate, sharper red emission and larger stimulated emission cross-section and the results indicated prepared luminescent polymers including Eu(tpb-D)₃(Tppo)₂ showed promising results for applications in novel organic Eu(III) devices. Additionally, the Eu(III) complexes and luminescent PMMA showed good thermostabilization.     

一个由4,4′-(丁烷-1,4-二氧基)-二苯甲酸和双咪唑配体构筑的三重穿插金属有机骨架化合物(英文)

采用水热法合成了1个二维缠结金属有机框架化合物[Cu(bbi)0.5(boba)]n(1)(bbi=1,1′-(1,4-丁烷基)-二(咪唑);H2boba=4,4′-(丁烷-1,4-二氧基)-二苯甲酸),并通过元素分析、红外光谱和单晶X-射线衍射对其进行了结构表征。结构分析显示:化合物1是具有聚轮烷和聚锁烃结构特征的三重平行穿插网络。此外还研究了它的荧光和热稳定性。     

Evidence for a Bulky Unit of a Pillar[5]arene Flipping in the Solid State

It is well known that pillar[5]arenes have two most stable conformations (pS and pR) in their crystal structures. Because of the intramolecular H‐bonding interactions, substituents, temperature, solvent and so on, the rotational behaviors of the phenolic units on pillararenes are also common. This paper showed some other kinds of conformations in the functionalized pillar[5]arenes and gave evidence for a bulky unit (1,4‐methoxycarbonylmethoxybenzene unit) flipping in the solid state. The presence of hydrogen bonding facilitated the intermolecular self‐assembly in terms of energy‐minimized packing in the crystals. Thus, the main driving force for the flipping of this bulky unit might be both the intramolecular hydrogen bonding between the phenolic units on pillararenes and quadrupolar hydrogen bonding between the host and water. This paper helps us to have a better understanding on the conformations of pillar[5]arenes.     

新型吡唑啉衍生物的合成及其对Fe(Ⅲ)的选择性识别

以芳酮和芳醛为原料,在Na OH/Et OH存在下经缩合反应制得中间体芳烯酮(3);3与肼经环合反应合成了5个新型的含荧光基团的吡唑啉衍生物(5a~5e),其结构经1H NMR,13C NMR和IR表征。并利用UVVis和FL研究了5a~5e对金属离子的选择识别性能。结果表明,5a~5e对Fe(Ⅲ)有较好的选择性识别。