Design, synthesis of diaryl ether tyrosine kinases inhibitior and study of their antiaumor activities

肿瘤是机体在各种致癌因子作用下，细胞内遗传物质发生改变，进而导致基 因表达失常，细胞异常增殖的新生物。以一些与肿瘤细胞分化增殖相关的细胞信 号转导通路的关键酶作为药物筛选靶点，发现选择性作用于特定靶点的高效、低 毒、特异性强的新型抗癌药物——酪氨酸激酶抑制剂已成为当今抗肿瘤药物研究 开发的重要方向。 本文结合计算机辅助设计和文献分析，以二芳醚为基础利用生物电子等排体 理论用酰胺结构代替脲，设计合成了五个系列的二芳醚酰胺类化合物，并对这些 化合物进行抗肿瘤活性筛选。本文分别选取HepG2、A549及HT-29作为研究对 象。 实验结果表明：(1)在所设计的四类化合物中，N-(单...Tumor is an abnormal proliferation of tissue as a result of abnormal growth or division of cells, which can be caused by genetic mutations. Some of the key enzymes in tumor cell differentiation and cell proliferation-related signal transduction pathway as a target for drug screening and found that selectively act on specific targets efficiency, low toxicity and ...学位：理学硕士院系专业：药学院_药物化学学号：3232011115329

单个纳米颗粒的光散射检测技术进展

纳米颗粒因其在生物医学和生物分析领域具有重要的应用前景而备受关注.单个纳米颗粒的光散射检测技术是一种简单、有效地对纳米颗粒的尺寸、尺寸分布及浓度等进行表征的分析方法,尤其在揭露纳米颗粒的内在异质性方面具有独特优势.然而瑞利散射强度随粒径减小呈六次方衰减,使得小尺寸单个纳米颗粒的检测非常具有挑战性.本文对近年发展起来的多种单个纳米颗粒的光散射检测技术进行综述

Development of a Single-molecule Flow Analyzer

A single-molecule flow analyzer based on laser induced fluorescence and hydrodynamic focusing was developed in our lab. There were three key aspects of this design for achieving single molecule detection sensitivity: (1) a detector with a high photon-detection efficiency(>65% for avalanche photo-diode detector); (2) a small probe volume obtained by sheath-protected, hydrodynamically focused sample stream to reduce background; and (3) a slow flow to provide extended dwell time(milliseconds) in the probe volume so that more fluorescence cycling can occur. The single molecule detection sensitivity was demonstrated by the successful detection of single phycoerythrin molecules. The house-constructed single-molecule flow analyzer was applied to DNA fragment sizing with linear correlation between DNA fragment length and mean burst size.国家自然科学基金(批准号:20645001,20675070);; 福建省科技厅科研基金(批准号:2005NZ1013);; 教育部留学回国人员科研启动基金;; 2006年度福建省新世纪优秀人才支持计划;; 2007年度教育部新世纪优秀人才支持计划基金资

The Interaction Mechanism Between Paclitaxel and HSA

以人血清白蛋白(HSA)为实验材料,通过荧光光谱、等温滴定量热及紫外-可见吸收光谱等技术研究化疗药物紫杉醇与其的结合机理.荧光光谱检测结果表明:紫杉醇主要通过氢键和范德华力与HSA结合,并引起其内源荧光的猝灭.在温度为303k下,二者间的结合常数为10.7x103 l/MOl.紫外-可见吸收光谱检测发现,随着紫杉醇浓度的增加,HSA在278nM处的吸收峰增大,证明二者结合后HSA的构象发生了改变.等温滴定量热实验则进一步说明二者的结合是一个自发进行的放热反应,在温度为303k下结合常数为8.8x103 l/MOl,焓变、熵变及吉布斯自由能分别为-99.1kJ/MOl,-183.6J/(MOl·k)和-43.5kJ/MOl.本研究为紫杉醇在血液中的运输及传递提供理论支持.The interaction mechanism of chemotherapy drugs paclitaxel with human serum albumin(HSA)was studied using fluorescence spectroscopy,isothermal titration calorimetry,and UV spectroscopy.The result of fluorescence experiment showed that the intrinsic fluorescence of HSA was quenched by the binding of paclitaxel,with an binding constant of 10.7×103 L/mol at 303K,and the main forces were hydrogen bonds and van der Waals forces.The result of UV-visible spectroscopy experiment showed that the absorption peak of HSA at 278nm increased with the increase of concentrations of paclitaxel.Such phenomenon implied that the interaction might lead to the conformation change of HSA.Isothermal titration calorimetry experiment further confirmed that the interaction between HSA and paclitaxel is a spontaneous process of exothermic reaction,of which the binding constant,enthalpy change,entropy,and Gibbs free energy are 8.8×103 L/mol,-9.9kJ/mol,-183.6J/(mol·K)and-19.1kJ/mol,respectively at 303K.Our current study provides a theoretical explanation for processes of transport and delivery of paclitaxel in the blood.中央高校基本科研业务费专项资金项

局部时间步法在低马赫燃烧模拟中的适用性研究

在复杂燃烧模拟中由于整场流速的不均匀性和局部网栺尺寸的差异,各局部流场区域的CFL数差异较大.传统的基于整场最大CFL数定义的整体时间步法严重制约计算效率.本文首次考察了基于当地CFL数限制的局部时间步法在低马赫数湍流燃烧模拟中的适用性.对开放空间中甲烷池火(1 065万网栺)和封闭空间建筑火灾(320万网栺)的大涡模拟表明,采用局部时间步法相比于整体时间步法分别实现了6倍和8倍的加速比.加速比随网栺尺度减小呈增加趋势.研究迚一步从两个斱面验证了局部时间步法在低马赫数燃烧模拟中的准确性:(1)与实验数据的对比表明,由于低马赫数燃烧的准稳态特性,局部和整体时间步法均较为准确地预测了温度的时间变化特性;(2)对时均流场的比较表明,陣微量痕迹物(质量分数小于0.1%)以外,两种斱法对时均温度、时均速度和氧气体积分数的预测差异均较小.研究中还对现有的Pa SR湍流燃烧模型和压力求解算法迚行了改迚和优化,以分别提高其物理准确性和鲁棒性.</p

CeO2/Si薄膜的紫／蓝光跃迁

利用双离子束外延技术制备了CeO2/Si薄膜，观察到了CeO2室温蓝光发光以及低温紫光致发光(PL)现象．利用XRD和XPS对薄膜结构及价态进行分析后表明，Ce02的发光机制是由于电子的Ce4f→O2p跃迁和缺陷能级→O2p能级跃迁共同作用的结果，并且这些缺陷能级位于Ce4f能级上下1eV的范围内

离子束外延生长半导体性锰硅化合物

利用质量分析的低能双离子束外延技术得到了半导体性的锰硅化物，Mn_(27)Si_(47)和Mn_(15)Si_(26)。俄歇电子谱谐深度组分测量结果表明，在单晶Si的表面淀积了一薄层厚度约为37.5nm的Mn，另一部分Mn离子成功注入进Si基底里，注入深度为618nm。在840℃条件下在流动N_2气氛中对生长样品进行退火，X射线衍射结果表明退火后Mn_(27)Si_(47)和Mn_(15)Si_(26)结晶更好