A series of pyrimidine-2,4-diamine analogues were designed and synthesized. Their anticancer activity and the underlying mechanism against colorectal cancer (CRC) HCT116 cells and non-small cell lung cancer (NSCLC) A549 cells were investigated. The results demonstrated that the active compound Y18 significantly inhibited cancer cell proliferation by inducing robust cell cycle arrest and cell senescence through the persistence of DNA damage. Additionally, Y18 exhibited significant inhibitory effects on the adhesion, migration and invasion of cancer cells in vitro. Mechanistically, Y18 achieved these anticancer activities by suppressing GTSE1 transcription and expression. Y18 also effectively inhibited tumor growth in vivo with minimal side effects. Furthermore, Y18 exhibited a suitable half-life and oral bioavailability (16.27%), with limited inhibitory activity on CYP isoforms. Taken together, these results suggested that Y18 could be a potential chemotherapeutic drug for cancer treatment, particularly in cases of GTSE1 overexpressed cancers.

Cubic-phase magnesium-aluminum spinel (MAS) has attractive optical, mechanical, and thermal properties and has been widely used as transparent ceramics in a number of applications. However, the processing of MAS transparent ceramics typically requires pre-sintering and hot isostatic pressing (HIP) both at very high temperatures (e.g., above 1600 degrees C) over an extended time, which coarsens the microstructure thus impairing mechanical properties. There is an urgent need to lower the sintering temperature while maintaining high optical transparency. Here we reported new progress in combining two-step sintering in the pressureless pre-sintering step and low-temperature HIP in the post-treatment step, using high-quality green bodies produced by pressure filtration. With this strategy, high-quality MAS transparent ceramics are delivered. The main benefits include 200 degrees C lower HIP temperature, a 33% smaller average grain size of 350 nm, and a higher hardness of 14.8 GPa. Such a method could be extended to many other transparent ceramics.

Antibiotics can kill bacteria, but their continued use can easily lead to drug resistance, particularly the main pathogenic bacteria of periodontitis, Porphyromonas gingivalis. However, to avoid drug resistance, carbon quantum dots (CDs) have great potential as a bioactive material in antimicrobial therapy. Herein, we use ornidazole as raw material to prepare CDs of different sizes by microwave irradiation and screen CDs with fluorescence and bacteriostatic properties. The inhibition experiments and live/dead assays of P. gingivalis exhibited outstanding antibacterial effects. This research aimed to develop nano-level antibacterial active materials that also have fluorescence traceability. This study offers a different method for the development of multifunctional CDs, provides valuable strategies for the treatment of diseases associated with P. gingivalis, and predicts great application prospects in the field of biomedicine.

利用基于标准PBE0泛函的杂化密度泛函理论计算了Sr2 MgSi2 O7中本征缺陷、缺陷复合对及镧系离子的缺陷形成能、热力学转变能级以及光跃迁能级,以研究它们在Sr2 MgSi2 O7:Eu2+,Dy3+的热致发光和长余辉发光过程中所起的作用.PBE0计算的形成能结果表明,缺陷VO、SrMg、MgSr和SrMg-MgSr较容易在还原气氛下制备的Sr2 MgSi2 O7材料中生成.基于PBE0计算的基质带隙(7.18 eV)和缺陷形成能,获得了上述较易形成的缺陷与复合对以及镧系离子的热力学转变能级和光跃迁能级.根据理论计算结果与实验所确定的陷阱深度的直接对比,电中性及带一个负电荷的氧空位与Dy3+离子可以作为该材料中的电子陷阱,从而有助于其热致发光和长余辉发光.本研究的目的是利用第一性原理研究方法深入理解Sr2 MgSi2 O7:Eu2+,Dy3+的热致发光和长余辉发光机理,从而作为实验研究手段的一种有效补充.

Indoleamine 2,3-dioxygenase 1 (IDO1) as a key rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism plays an important role in tumour immune escape. Herein, a variety of secondary sulphonamides were synthesised and evaluated in the HeLa cell-based IDO1/kynurenine assay, leading to the identification of new IDO1 inhibitors. Among them, compounds 5d, 5l and 8g exhibited the strongest inhibitory effect with significantly improved activity over the hit compound BS-1. The in vitro results showed that these compounds could restore the T cell proliferation and inhibit the differentiation of naïve CD4+ T cell into highly immunosuppressive FoxP3+ regulatory T (Treg) cell without affecting the viability of HeLa cells and the expression of IDO1 protein. Importantly, the pharmacodynamic assay showed that compound 5d possessed potent antitumour effect in both CT26 and B16F1 tumours bearing immunocompetent mice but not in immunodeficient mice. Functionally, subsequent experiments demonstrated that compound 5d could effectively inhibit tumour cell proliferation, induce apoptosis, up-regulate the expression of IFN-γ and granzyme B, and suppress FoxP3+ Treg cell differentiation, thereby activate the immune system. Thus, compound 5d could be a potential and efficacious agent for further evaluation.

无机化学课程热化学部分关于焓的概念,引入太直接,论述太抽象,公式推导不严谨,学生们的接受程度很低.鉴于此,文章在融合了国内外关于焓的物理意义的学术探讨的基础上,以通俗易懂的表述手法,从教学角度探讨焓及焓变的物理意义,促进学生理解,并为其后续课程相关知识的学习打下一定的基础.

Using pyrazine-2-carboxylic acid (2-Hpzc), 3,5-pyridinedicarboxylic acid (3,5-H(2)PDA) and oxalic acid (H(2)ox) as ligands, nine Ag-Ln coordination polymers are synthesized by hydrothermal methods: {[LnAg(2-pzc)(2)(ox)]center dot H(2)ox} (Ln=Pr (1), Nd (2), Sm (3), Eu (4)), [LnAg(3,5-PDA)(ox)(H2O)](n), (Ln=Pr (5), Nd (6)), [LnAg(3,5-PDA)(3,5-HPDA)(ox)(0.5)(H2O)(2)](n) (Ln=Sm (7), Dy (8), Ho (9)). All of them possess the 3D network structure, i.e., coordination polymers 1 similar to 4 are isomorphic and connected by 2-pzc(-) and ox(2-), while coordination polymers 5 similar to 9 use 3,5-PDA(2-) and ox(2-) as bridging ligands. Photophysical properties of these coordination polymers are studied, and they show characteristic emissions of corresponding Ln(III) ions which should be attributed to the sensitization of the Agligand section (d-block). In addition, under the co-action of crystal field and 4d orbits of Ag(I) ion, the 4f orbits of Ln(III) ions are tuned and cause obvious shift of partial energy levels, which present shifts of the corresponding NIR emission bands and can be corroborated in their UV-Vis-NIR absorption spectra. CCDC: 1817276, 1; 1817247, 2; 1817248, 3; 1817249, 4; 1817251, 5; 1817255, 6; 1817269, 7; 1817280, 8; 1817285, 9.

A series of coordination polymers, ([LnZn(2,3-pydc)(1,3-bdc)(OH)(H2O)(m)]center dot H2O}n, (Ln = Sm 1, Eu 2, Gd 3, Tb 4, Dy 5, Er 6, Yb 7, Pr 8, Nd 9), (1-7, m 1; 8, 9, m= 2), (2,3-H(2)pydc = pyridine-2,3-dicarboxylic acid, 1,3-H(2)bdc = isophthalic acid), are synthesized by the hydrothermal method and their crystal structures are determined by single-crystal X-ray diffraction. Structural analysis shows that coordination polymers 1-9 present two-dimensional layered structures and all of them are crystalized in triclinic system with space group Pt Hereinto polymers 1-7 are isomorphous, while polymers 8 and 9 are also isomorphous and each of them includes one more coordinated water molecule than others. All coordination polymers are characterized by IR, UV-Vis-NIR and fluorescent spectra, and the luminescent properties are the research emphasis. In addition, except for polymer 3, the other eight Zn-Ln polymers exhibit the characteristic luminescence of corresponding Ln(III) ions, which should be owing to the sensitization of the Zn-Ligand moiety. With the influence of the crystal field and the introduction of Zn(II) ion, the internal energy levels of the system are tuned, which is reflected by shift and split of the partial characteristic bands of Ln(III) ions in their UV-Vis-NIR absorption spectra and NIR emission spectra, and both can corroborate each other. (C) 2018 Elsevier B.V. All rights reserved.

Two base-decavanadates coordination polymers [H2V10O28]0.5Ni(phen)3 (1) and [(C4H14N2)2]·[Zn(H2O)6][V10O28]·6H2O (2) (phen = 1,10-phenanthroline) have been synthesized and characterized. They composed by the ligand, transition metal ions, and decavanadates, and both compounds are stable three-dimensional supramolecular structure due to exist of a multitude of hydrogen bonding interactions. The transition metal coordination modes are similar in compounds 1 and 2 as the six-coordinated octahedral structures. However, their coordination atoms are manifestly different. The Ni atom is coordinated with the ligand of phen and coordinated by the nitrogen atom, and the zinc atom is coordinated with oxygen in the water. The electrochemical measurement of cyclic voltammetric and electrocatalytic activities shows that compounds 1 and 2 have good electrochemical properties of hydrogen peroxide reductive.

Reactive oxygen species (ROS), especially HOCl/ClO-, have been demonstrated to play essential roles in both physiological and pathological processes, and an abnormal level of HOCl/ClO- is related to some diseases. In this work, a very fast responsive (within 30 seconds) porphyrin-based fluorescent probe, TPP-TCF, for ClO- with a NIR emissive wavelength was prepared. This probe exhibited excellent selectivity towards ClO- and would not be interfered with by other ROS and typical nucleophiles. The limit of detection (LOD) for ClO- was evaluated to be 0.29 μM, indicating high sensitivity towards ClO-. In further bioimaging experiments, TPP-TCF displayed low-cytotoxicity and good cell penetrability for recognizing exogenous ClO- in HeLa cells. Moreover, this probe was successfully applied in imaging endogenous ClO- in living animals.

Based on the reported IDO1 inhibitor U-3i, 11 phenylsulfonamide derivatives were designed and synthesized by adopting bioisosterism and molecular docking technology. The inhibitory activities of the target compounds against IDO1 were determined by the HeLa cell-based kynurenine assay. The results demonstrated that most compounds showed different degrees of inhibitory effects on IDO1. Among them, compounds 3b and 3e displayed the most potent activity and could reverse IDO1-mediated immune suppression, which might be worth of further investigation.

Six Zn-Ln coordination complexes, [Nd2Zn2(C6H5COO)10(Imh)2(H2O)2] (1), [Pr2Zn2(C6H5COO)10(Imh)2(H2O)2] (2), [ErZn2(C6H5COO)7(Imh)2] (3), [HoZn2(C6H5COO)7(Imh)2] (4), [EuZn2(C6H5COO)7(Imh)2] (5), [TbZn2(C6H5COO)7(Imh)2] (6) (C6H5COOH=benzoic acid, Imh=imidazole) have been synthesized under hydrothermal conditions and their crystal structures have been characterized by single crystal X-ray diffraction. All complexes are crystallized in triclinic system, with space group Pī. Complexes 1 and 2 are isomorphous with tetranuclear molecular structure and complexes 3–6 are isomorphous and trinuclear molecular complexes. All complexes are characterized by IR, UV–Vis–NIR and luminescent spectra in the visible and near-infrared (NIR) regions at room temperature. The study of luminescent properties indicates that all complexes exhibit the characteristic emission bands of corresponding Ln(III) ions, which should be attributed to sensitization from d-block and ligands after introducing Zn(II) ion and ligands into the system of Ln(III) complexes. Moreover, the NIR emission bands of complexes 1–4 exhibit shift and split, which can be evidenced in their UV–Vis–NIR absorption spectra.

Nine novel Ag-Ln coordination polymers, {[LnAg(2,6-PDA)(2)(H2O)(3)]mH(2)O}(n) (Ln=Pr 1, Nd 2, m=2; Ln=Sm 3, Gd 4, Dy 5, Tb 6, m=3; Ln=Eu 7, Ho 8, Er 9, m=1; 2,6-PDA=pyridine-2,6-dicarboxylic acid), were synthesized under hydrothermal methods. They were characterized by single-crystal X-ray diffraction, elemental analysis, IR, UV-Vis-NIR (Ultraviolet-Visible-Near Infrared) absorption and fluorescent emission spetra. In crystals, pyridine-2,6-dicarboxylates adopt four coordination modes to bridge Ag(I) and Ln(III) ions, i.e., polymers 1 and 2 present 2D layers and polymers 3-9 possess 1D chain structure. The emphasis is on the research of luminescent properties. All of the polymers show characteristic emissions owing to the effective sensitization from the Ag-ligand section with the introduction of Ag(I) ion. Due to the influence of crystal field and 4d orbitals of Ag(I), the NIR emission bands of Ln(III) polymers present shift, broad and split, and some absorption bands of f-f* transitions also show shift, broad and split in their UV-Vis-NIR spectra, so the two spectra can evidence each other.

Indoleamine 2,3-dioxygenase 1 (IDO1) is frequently hijacked by tumors to escape the host immune response, and the enzyme is now firmly established as an attractive target for cancer immunotherapy. To identify novel IDO1 inhibitors suitable for drug development, a scaffold-hopping strategy combined with the average electrostatic potentials calculation was ultilized to design novel benzoxazolinone derivatives. Among these, compounds 7e, 7f and 9c exhibited the inhibitory potency in the low micromolar range and displayed negligible level of cytotoxicity against HeLa cells. Treatment with these three compounds promoted the proliferation of T lymphocyte and led to the dramatic decrease of regulatory T cells in the B16F1 cells and naïve T cells co-culture system. Subsequent spectroscopic experiments suggested that these benzoxazolinones formed a coordinate bond with the heme iron to stabilize the complex. This study suggested that the benzoxazolinone was an interesting scaffold for discovering novel IDO1 inhibitors, and these compounds are attractive candidates for further development.

Indoleamine-2,3-dioxygenase-1 (IDO1) is an attractive target for cancer immunotherapy. Herein, a series of novel imidazoleisoindole derivatives were prepared and evaluated for their ability to inhibit IDO1. Among these, derivative 11r was the most active compound with nanomolar potency in the Hela cell-based assay, while showed negligible cellular toxicity. UV-visible spectra study demonstrated that compounds 11p and 11r bound to IDO1 and coordinated with the heme iron. Furthermore, they could significantly promote T cell proliferation, increase IFN-γ production, and reduce the numbers of Foxp3+ regulatory T cells. Finally, induced fit docking (IFD) and quantum mechanics/molecular mechanics (QM/MM) calculation were performed to understand the interactions of these compounds to IDO1 protein, which provided a comprehensive guide for further structural modification and optimization.

Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as an attractive target for cancer immunotherapy. To rationalize the detailed interactions between IDO1 and its inhibitors at the atomic level, an integrated computational approach by combining molecular mechanics and quantum mechanics methods was employed in this report. Specifically, the binding modes of 20 inhibitors was initially investigated using the induced fit docking (IFD) protocol, which outperformed other two docking protocols in terms of correctly predicting ligand conformations. Secondly, molecular dynamics (MD) simulations and MM/PBSA free energy calculations were employed to determine the dynamic binding process and crucial residues were confirmed through close contact analysis, hydrogen-bond analysis and binding free energy decomposition calculations. Subsequent quantum mechanics and nonbonding interaction analysis were carried out to provide in-depth explanations on the critical role of those key residues, and Arg231 and 7-propionate of the heme group were major contributors to ligand binding, which lowed a great amount of interaction energy. We anticipate that these findings will be valuable for enzymatic studies and rational drug design.

Periplakin (PPL), a member of the plakin protein family, has been reported to be down-expressed in urothelial carcinoma. The role of PPL in human colorectal cancer, however, remains largely unknown. Also little is known about the contribution of PPL to the malignant property of colorectal cancer and the intracellular function of PPL. In this study, we demonstrated that PPL was apparently down-expressed in colon carcinomas compared with normal and para-carcinoma tissues, which was correlated with the tumor size. Enforced expression of PPL in HT29 cells inhibited its proliferation evidenced by decreased expression of phosphorylated ERK and PCNA. Furthermore, PPL overexpression could reduce metastasis and epithelial-mesenchymal transition (EMT) of HT29 cells, with decreased expression of N-cadherin, Snail, Slug and α-SMA while increased expression of E-cadherin. On the contrary, the PPL knockdown could promote the cell proliferation, migratory, invasive and EMT ability of HT29 cells. Moreover, enforced expression of PPL induced G1/G0 cell cycle arrest, with decreased cyclin D1, p-Rb and increased expression of p27kib, which could be reversed by PPL knockdown. In addition, PPL overexpression inhibited the growth of colon cancer allograft in vivo. Taken together, acted as a tumor suppressor in colon cancer progression, PPL could be a new biomarker or potential therapeutic target in colon cancer.

Structural chemistry is a basic professional course in chemistry depamnent, which is also rather difficult for most teachers and students due to its nonobjective concepts and methods. This paper proceeding from questions met in our daily teach- ing, has introduced opinions on the rules and principles in teaching and learning of structural chemistry, which may provide some referential experience for promoting the quality of teaching and personnel training.

A novel Ni(II) coordination polymer [Ni(dtba)(4,4'-bpy)] (1, H(2)dtba = 2,2'-dithiobisbenzoic acid, 4,4'-bpy = 4,4'-bipyridine) has been synthesized by H(2)dtba and Ni(CH3COO)(2)center dot 4H(2)O with exo-bidentate rigid ligand 4,4'-bpy by using hydrothermal method, and its structure was determined by single-crystal X-ray diffraction. X-ray crystal structure analysis reveals that complex 1 crystallizes in monoclinic, space group C-c with a = 11.7624(9), b = 18.7933(19), c = 10.3071(11) angstrom, beta = 97.6510(10)degrees, V = 2258.2(4) angstrom(3), Z = 4, C24H16N2NiO4S2, M-r = 519.22, D-c = 1.527 g/cm(3), mu = 1.079 mm(-1) and F(000) = 1064. The structure was solved by direct methods and refined to R = 0.0434 and wR = 0.1000 for 3281 observed reflections (I > 2 sigma(I)). The coordination environment of Ni(II) is a distorted octahedron, and a three-dimensional structure was formed with the coordination effect of dtba(2-) and 4,4'-bpy ligands. The topological analysis reveals.. that the whole framework of 1 is a 2-nodal net of (5(2).6)(5(3).6(4).7(2).8) topology. The thermal stability and XRD pattern of 1 were also investigated.

One novel dysprosium(III) complex exhibiting distinctive new two-dimensional (2D) topological net based on pyridyl-carboxylate ligand, namely DyL(HL)·2H2O (1) (H2L=5-((pyridine-3-ylmethyl)amino)isophthalic acid), was obtained by the reactions of the dysprosium nitrate with H2L under hydrothermal condition. In the structure of complex 1, the metal centers act as rare 5-connected topological blocks and the 2D layer consisted of μ2/μ3-ligands and 5-connected Dy(III) centers is the first example of 2-nodal net of (42.6)(42.67.8) topology. In complex 1, the 2D layers are further stacked to form its three-dimensional structure, which is stabilized by abundant non-covalent interactions including π⋯π interactions between its aromatic benzene and pyridine rings as well as various hydrogen bonds.