苯丙氨酸铁卟啉配合物的合成及其催化环氧化性质

文章合成了两个新的手性卟啉配合物-尾式L（D）-苯丙氨酸铁Hh啉,并通过紫外光谱和质谱对其结构进行了表征。利用这两个化合物进行了苯乙烯的催化环氧化研究,分别考察了不同溶剂和不同轴向配体的影响。实验结果显示尾式L（D）-苯丙氨酸铁卟啉催化苯乙烯氧化的产物不具有对映体选择性。在不同溶剂中的环氧化物产率：乙腈〉二氯甲烷〉甲醇。在不同轴向配体作用下的产率为：吡啶〉4．硝基咪唑〉咪唑。     

原子转移自由基聚合法（ATRP）制备聚丙烯酰胺

以苄基氯为引发剂,氯化亚铁为催化剂,三苯基膦为配体研究了丙烯酰胺在N,N-二甲基甲酰胺中的原子转移自由基聚合,考察了聚合时间、催化剂与配体的摩尔配比、温度等因素对单体转化率、分子量的影响。结果表明：80℃下,[AM]/[C6H5CH2Cl]/[FeCl2]/[PPh3]=100/1/0.5/1时,聚丙烯酰胺分子量随单体转化率增加线性增大,ln[[MM]]0与聚合时间呈线性关系,温度对聚合特征有较大影响。     

非均相金属钯配体催化剂的研究进展

Suzuki-Miyaura反应是一类具有工业化应用前景的C-C键合成反应。反应多数是在均相金属钯配体催化剂催化下完成。均相催化具有催化效率高、产品选择性好等优点,但催化剂回收困难,增加了反应成本,限制了其应用。非均相金属钯配体催化剂是将均相金属钯配体催化剂固载到载体上,使其在不影响反应活性和选择性的同时,实现循环使用,已成为Suzuki-Miyau-ra反应的研究热点。对几年来以有序介孔材料MCM-41和SBA-15、无机载体SiO2和Al2O3、聚苯乙烯和聚乙二醇等合成材料以及天然高分子材料为载体,制备非均相金属钯配体催化剂的方法及其催化性能进行了综述。     

α-氨基酸在L-苯丙氨酸手性配体交换色谱固定相上的分离研究

合成了L—苯丙氨酸硅胶键合手性配体交换色谱固定相，并用于α—氨基酸的直接光学分离。详细考察了流动相pH、金屑离子浓度、流速、进样量以及柱温等因素对分离效果的影响，从而进一步优化了色谱分离条件。     

巯基丙酸保护的纳米银制备及热分解行为研究

以双官能团配体巯基丙酸(MPA)为保护剂, 通过配体置换法和液相化学还原法制备得到纳米银.考察了双官能团配体对纳米银的制备及热分解的影响.配体置换法制备的纳米银粒径为50 nm左右,化学还原法制备的纳米银粒径为10 nm左右.元素分析结果和X射线光电子能谱表明MPA通过S原子与Ag原子形成共价键,同时通过烷基链之间的氢键作用及范德华力形成多层保护剂保护的纳米银.将纳米银在200 ℃下烧结并对烧结产物进行表征,结果表明加热使得C-S键断裂,Ag/MPA热分解形成硫化银.     

蛋白质与配体相互作用机制研究方法进展

蛋白质与配体间的相互作用在医药、食品领域中意义重大，综述了光谱法、等温滴定量热法和分子对接在讨论溶液中的蛋白质与配体作用机制中的应用，其中光谱法可以推测蛋白质与配体间弱相互作用和蛋白质的构型变化，等温滴定量热法能够分析蛋白质和配体间的结合常数和结合位点数以及热力学参数，分子对接对于上述两种方法起到了补充和佐证的作用。这些方法为后续进一步考察蛋白质与小分子之间结合作用提供了多种方法支持。     

一种含末端炔基的手性亚磷酰胺酯配体的合成

手性亚磷酸酰胺酯配体在不对称催化反应中有着广泛的应用。末端带官能团的手性亚磷酰胺酯配体的合成却很少有报道。以炔丙基溴、对羟基苯甲醛、S-BINOL为原料通过烷基化,亲核加成-消除,还原以及膦酰化反应以较高收率制得含炔键的手性亚磷酰胺酯配体。目标产物经过了1H NMR、13C NMR、31P NMR、LC-MS表征。为探讨该类配体以及"点击化学方法"负载手性催化剂在不对称催化反应中的应用研究奠定了基础。     

过渡金属催化的碳-氮键偶联反应的研究

过渡金属催化的偶联反应是形成碳-氮键最为有效的手段之一,己经被广泛地应用于有机化学的许多领域。近年来对偶联反应的研究和报导层出不穷,主要集中在寻找新的催化剂,配体和催化体系进行反应,扩大反应的应用领域。采用过渡金属催化有机反应来构建C-N键是一种有效的合成策略。铜催化剂具有价格便宜、低毒等优点,因而近年来受到广泛的关注。本论文以过渡金属催化的碳-氮键偶联反应为研究内容,为了得到最优的反应条件,首先考察水介质中各种铜催化剂(Cu、CuO,Cul,CuBr,CuCI,Cu(0Ac)_2,CuBr_2等)对反应的催化性能,筛选出具有较好催化活性的铜催化剂,然后,考察常见配体和铜催化剂对反应的影响,并从催化剂用量、物料比、温度、压力、反应时间、原料混合程度等方面来探索水介质中碳氮键构建反应的技术路线。在产物的分离与表征中,用薄层液相色谱和柱色谱分离合成中间体以及目标产物,采用傅立叶如外光谱来表征中间体和目标化合物的特征吸收峰,核磁共振氫谱(1HNMR)、破谱(13CNMR)来表征目标化合物结构特征。     

氢分子键长、键能的精确计算

用宏观方法考察静电引力场,提出静电场很可能有流体特性这一假设,以此为基础,建立氢分子成键模型。即假定氢分子键能和结构之间存在联系,认为两个氢原子结合成氢分子后平均电势能密度守恒,归纳出氢分子键能和结构之间的方程组,用该方程式对基态氢分子键长、键能进行了计算,最终得到氢分子键长、键能的计算值为R_e=0.7412 7)?,D_e=4.7467e V,与实验值较好的吻合,成键模型直观,物理意义明确,且计算方法简单,计算过程不含任何人为定义的参数。     

8-羟基喹啉衍生物金属配合物的发光研究

通过Claisen重排反应合成了7-烯丙基-8-羟基喹啉配体,并且合成了金属离子Zn~(2+)、Cu~(2+)和Cd~(2+)的配合物。研究了配体及金属配合物的紫外吸收光谱、红外光谱以及光致发光现象。结果表明,配体与金属离子之间形成了稳定配合物,在紫外光激发下,Zn-配合物和Cd-配合物分别发出黄光和蓝-绿光,而Cu-配合物表现为配体的发光。     

Interaction between medetomidine and alkyd resins: NMR and FTIR investigation of antifouling marine paint model systems

The synthesis and optimization of novel bioactive components is key to the development of antifouling marine coatings. It was recently demonstrated that medetomidine (MM) has perfect antibarnacle behavior along with good ecological properties. To investigate the applicability of MM in self‐polishing marine paints, a large set of mixtures of MM with two commercial alkyd resins (ARs) was prepared. The nature and strength of the intermolecular interaction as a function of composition in both the liquid and solid states were studied using NMR and FTIR techniques, respectively. It was found that at low concentrations MM molecules were coordinated to alkyd resin chains by hydrogen bonding. This interaction had a multidentate character (i.e., one molecule of MM interacted with several ? COOH species of ARs) that resulted in stronger bonding between the two compounds. However, at higher MM concentrations an ionic association between the two compounds began, which at a large MM content resulted in microphase separation. It was noted that the strong interaction between medetomidine and the alkyd resins investigated was a positive factor for the application of these compounds in self‐polishing marine paints. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 2006     

Explanation of the Formation of Complexes between Representatives of Oxazolidinones and HDAS-β-CD Using Molecular Modeling as a Complementary Technique to cEKC and NMR

Molecular modeling (MM) results for tedizolid and radezolid with heptakis-(2,3-diacetyl-6-sulfo)-β-cyclodextrin (HDAS-β-CD) are presented and compared with the results previously obtained for linezolid and sutezolid. The mechanism of interaction of chiral oxazolidinone ligands belonging to a new class of antibacterial agents, such as linezolid, tedizolid, radezolid, and sutezolid, with HDAS-β-CD based on capillary electrokinetic chromatography (cEKC), nuclear magnetic resonance (NMR) spectroscopy, and MM methods was described. Principles of chiral separation of oxazolidinone analogues using charged single isomer derivatives of cyclodextrin by the cEKC method were presented, including the selection of the optimal chiral selector and separation conditions, complex stoichiometry, and binding constants, which provided a comprehensive basis for MM studies. In turn, NMR provided, where possible, direct information on the geometry of the inclusion complexes and also provided the necessary structural information to validate the MM calculations. Consequently, MM contributed to the understanding of the structure of diastereomeric complexes, the thermodynamics of complexation, and the visualization of their structures. The most probable mean geometries of the studied supramolecular complexes and their dynamics (geometry changes over time) were determined by molecular dynamics methods. Oxazolidinone ligands have been shown to complex mainly the inner part of cyclodextrin, while the external binding is less privileged, which is consistent with the conclusions of the NMR studies. Enthalpy values of binding of complexes were calculated using long-term molecular dynamics in explicit water as well as using molecular mechanics, the Poisson–Boltzmann or generalized Born, and surface area continuum solvation (MM/PBSA and MM/GBSA) methods. Computational methods predicted the effect of changes in pH and composition of the solution on the strength and complexation process, and it adapted the conditions selected as optimal during the cEKC study. By changing the dielectric constant in the MM/PBSA and MM/GBSA calculations, the effect of changing the solution to methanol/acetonitrile was investigated. A fairly successful attempt was made to predict the chiral separation of the oxazolidinones using the modified cyclodextrin by computational methods.     

Topological insulator metamaterials with tunable negative refractive index in the optical region

A blueshift tunable metamaterial (MM) exhibiting a double-negative refractive index based on a topological insulator (bismuth selenide, Bi₂Se₃) has been demonstrated in the near-infrared (NIR) spectral region. The potential of Bi₂Se₃ as a dielectric interlayer of the multilayer MM is explored. The optical response of elliptical nanohole arrays penetrating through Au/Bi₂Se₃/Au films is numerically investigated using the finite difference time domain (FDTD) method. The blueshift tuning range of the MM is as high as 370 nm (from 2,140 to 1,770 nm) after switching the Bi₂Se₃ between its trigonal and orthorhombic states.     

Synergistic Effects of Venetoclax and Daratumumab on Antibody-Dependent Cell-Mediated Natural Killer Cytotoxicity in Multiple Myeloma

The prognosis of multiple myeloma (MM) has drastically improved owing to the development of new drugs, such as proteasome inhibitors and immunomodulatory drugs. Nevertheless, MM is an extremely challenging disease, and many patients are still refractory to the existing therapies, thus requiring new treatment alternatives. Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 that shows efficacy in MM not only as a single agent but also in combination therapy, especially for MM patients with translocation t(11;14). However, many patients are refractory to this drug. Here, we treated the MM cell lines KMS12PE and KMS27 with a combination treatment of venetoclax targeting BCL-2 and daratumumab targeting CD38 to evaluate the synergistic cytotoxicity of these drugs in vitro. MM cell lines were co-cultured with natural killer (NK) cells at an effector:target ratio of 0.3:1 in the presence of serial concentrations of daratumumab and venetoclax, and the resulting apoptotic MM cells were detected by flow cytometry using annexin V. These results indicated that the antibody-dependent cell-mediated NK cytotoxicity was enhanced in KMS12PE and KMS27 cells harboring t(11;14) with a high BCL-2 expression, suggesting that the combination treatment of venetoclax and daratumumab should be especially effective in patients with these characteristics.     

Forchlorfenuron and Novel Analogs Cause Cytotoxic Effects in Untreated and Cisplatin-Resistant Malignant Mesothelioma-Derived Cells

Malignant mesothelioma (MM) is a currently incurable, aggressive cancer derived from mesothelial cells, most often resulting from asbestos exposure. The current first-line treatment in unresectable MM is cisplatin/pemetrexed, which shows very little long-term effectiveness, necessitating research for novel therapeutic interventions. The existing chemotherapies often act on the cytoskeleton, including actin filaments and microtubules, but recent advances indicate the ‘fourth’ form consisting of the family of septins, representing a novel target. The septin inhibitor forchlorfenuron (FCF) and FCF analogs inhibit MM cell growth in vitro, but at concentrations which are too high for clinical applications. Based on the reported requirement of the chloride group in the 2-position of the pyridine ring of FCF for MM cell growth inhibition and cytotoxicity, we systematically investigated the importance (cell growth-inhibiting capacity) of the halogen atoms fluorine, chlorine, bromine and iodine in the 2- or 3-position of the pyridine ring. The MM cell lines ZL55, MSTO-211H, and SPC212, and—as a control—immortalized Met-5A mesothelial cells were used. The potency of the various halogen substitutions in FCF was mostly correlated with the atom size (covalent radius); the small fluoride analogs showed the least effect, while the largest one (iodide) most strongly decreased the MTT signals, in particular in MM cells derived from epithelioid MM. In the latter, the strongest effects in vitro were exerted by the 2-iodo and, unexpectedly, the 2-trifluoromethyl (2-CF₃) FCF analogs, which were further tested in vivo in mice. However, FCF-2-I and, more strongly, FCF-2-CF₃ caused rapidly occurring strong symptoms of systemic toxicity at doses lower than those previously obtained with FCF. Thus, we investigated the effectiveness of FCF (and selected analogs) in vitro in MM cells which were first exposed to cisplatin. The slowly appearing population of cisplatin-resistant cells was still susceptible to the growth-inhibiting/cytotoxic effect of FCF and its analogs, indicating that cisplatin and FCF target non-converging pathways in MM cells. Thus, a combination therapy of cisplatin and FCF (analogs) might represent a new avenue for the treatment of repopulating chemo-resistant MM cells in this currently untreatable cancer.     

Electrochemical performance of gel-cast NiO-SDC composite anodes in low-temperature SOFCs

NiO-Ce_0.8Sm_0.2O_1.9 (SDC) composites were synthesized using gel-casting technique. The electrochemical performance of the gel-cast (GC) Ni-SDC cermet as anode was investigated contrast with that fabricated from traditional mechanical mixing (MM) technique using fuel cells with about 35 μm-thick SDC electrolyte and Sm_0.5Sr_0.5CoO₃-SDC cathode. Maximum power density of the cell with GC anode achieved 491 mW cm⁻² at 600 °C, over 100 mW cm⁻² larger than that with MM anode, inferring high catalytic activity of the GC anode. Impedance measurements on the fuel cell at open circuit showed that the anodic interfacial polarization resistance of the GC anode was 0.1 Ω cm² lower than that of the MM anode. Long-term stability of the cell with GC anode in hydrogen was also performed, which showed that it can stabilize at least 7 days.     

Dendritic Cell-Based Immunotherapy in Multiple Myeloma: Challenges,Opportunities, and Future Directions

Immunotherapeutic approaches, including adoptive cell therapy, revolutionized treatment in multiple myeloma (MM). As dendritic cells (DCs) are professional antigen-presenting cells and key initiators of tumor-specific immune responses, DC-based immunotherapy represents an attractive therapeutic approach in cancer. The past years, various DC-based approaches, using particularly ex-vivo-generated monocyte-derived DCs, have been tested in preclinical and clinical MM studies. However, long-term and durable responses in MM patients were limited, potentially attributed to the source of monocyte-derived DCs and the immunosuppressive bone marrow microenvironment. In this review, we briefly summarize the DC development in the bone marrow niche and the phenotypical and functional characteristics of the major DC subsets. We address the known DC deficiencies in MM and give an overview of the DC-based vaccination protocols that were tested in MM patients. Lastly, we also provide strategies to improve the efficacy of DC vaccines using new, improved DC-based approaches and combination therapies for MM patients.     

Expression Profiles of ASIC1/2 and TRPV1/4 in Common Skin Tumors

The acid-sensing ion channels ASIC1 and ASIC2, as well as the transient receptor potential vanilloid channels TRPV1 and TRPV4, are proton-gated cation channels that can be activated by low extracellular pH (pH_e), which is a hallmark of the tumor microenvironment in solid tumors. However, the role of these channels in the development of skin tumors is still unclear. In this study, we investigated the expression profiles of ASIC1, ASIC2, TRPV1 and TRPV4 in malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and in nevus cell nevi (NCN). We conducted immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express ASIC1/2 and TRPV1/4. Striking results were that BCCs are often negative for ASIC2, while nearly all SCCs express this marker. Epidermal MM sometimes seem to lack ASIC1 in contrast to NCN. Dermal portions of MM show strong expression of TRPV1 more frequently than dermal NCN portions. Some NCN show a decreasing ASIC1/2 expression in deeper dermal tumor tissue, while MM seem to not lose ASIC1/2 in deeper dermal portions. ASIC1, ASIC2, TRPV1 and TRPV4 in skin tumors might be involved in tumor progression, thus being potential diagnostic and therapeutic targets.     

Differentiated Epithelial- and Mesenchymal-Like Phenotypes in Subcutaneous Mouse Xenografts Using Diffusion Weighted-Magnetic Resonance Imaging

Epithelial-mesenchymal transition (EMT) is important for tumor metastasis. Detection of EMT protein expression and observation of morphological changes are commonly used to identify EMT. Diffusion-weighted magnetic resonance imaging (DW-MRI) and measuring apparent diffusion coefficient (ADC) values are noninvasive techniques for characterizing tumor microenvironments. We investigated the difference in ADC values between epithelial- and mesenchymal-like subcutaneous mouse xenografted tumors using DW-MRI. Epithelial-like MM189 PB-Klf4 and BL322 PB-Klf4 cells were generated from tumor suppressive Kruppel-like factor 4 (Klf4)-expressing mesenchymal-like MM189 and BL322 cells. The ADC values of xenografted tumors from epithelial-like MM189 PB-Klf4 and BL322 PB-Klf4 were significantly lower than those from their mesenchymal-like counterparts (p < 0.05 and p < 0.01, respectively). Our results suggested that DW-MRI is a potential tool for observing mesenchymal- or epithelial-like characteristics of subcutaneous xenografted tumors.