甲氨蝶呤/层状双金属氢氧化物的性能调控及细胞生物实验研究

在乙醇-水混合体系中,以氨水为沉淀剂共沉淀合成了甲氨蝶呤/层状双金属氢氧化物（MTX/LDH）纳米复合物,采用控制水热处理时间的方式来调控其性能。利用X-射线衍射（XRD）、透射电镜（TEM）和红外光谱（FT-IR）等表征手段,对其结构及形貌进行了表征。研究表明：MTX分子以单层倾斜或垂直方式插入LDH层间,随着水热处理时间的不同,MTX在层间的倾斜角度发生了变化;水热处理时间对产物的结晶度、粒径和层间排列方式都有影响,当水热处理时间为12h时,得到的MTX/LDH纳米复合物的结晶度最高,单分散性最好。在磷酸缓冲液中考察了MTX/LDH纳米复合物的缓释性能,结果表明样品均呈现出良好的缓释性能,释放速率先快后慢。重点考察了这几种MTX/LDH纳米复合物作用于肺癌细胞A549的细胞生物实验,研究表明这几种复合物对肺癌细胞A549都具有良好的抑制作用,其效果与纳米复合物的单分散性和粒径有密切的关系,单分散性越好,粒径分布越均匀,对A₅₄₉癌细胞的抑制效果越好。     

甲氨蝶呤/层状双金属氢氧化物的粒径调控及缓释性能研究

在乙醇-水混合体系中, 以氨水为沉淀剂共沉淀合成了甲氨蝶呤/层状双金属氢氧化物(MTX/LDH)纳米复合物, 首次采用控制沉淀剂滴加速率的方式来调控其粒径. 利用X-射线衍射(XRD)、透射电镜(TEM)和红外光谱(FT-IR)等表征手段, 对其结构及形貌进行了表征. 研究表明: MTX分子以单层倾斜方式插入LDH层间, 随着滴加速率不同, MTX在层间的倾斜角度发生了变化; 沉淀剂滴加速率对产物的结晶度、粒径和层间排列方式都有影响, 当沉淀剂滴加速率为0.100 mL/s时, 得到的MTX/LDH纳米复合物的结晶度最高, 粒径最大. 在磷酸缓冲液中考察了不同粒径MTX/LDH纳米复合物的缓释性能, 结果表明: 小粒径的MTX/LDH纳米复合物的载药量要高于大粒径的; 当MTX阴离子在层间的倾斜角度相似时, 粒径小的粒子释放速率较慢, 缓释效果优于粒径大的. 尤为重要的是我们探索出一条保证复合物阴离子在层间的倾斜角度相似的情况下, 制备不同粒径纳米复合物的新途径.     

甲氨蝶呤/锌铝层状双氢氧化物的合成以及生物效应研究

在乙醇-水混合体系中,采用改进的共沉淀法将甲氨蝶呤(MTX)插层组装到锌铝类水滑石(LDHs)层间形成了MTX/Zn-Al-LDHs纳米复合物,考察了不同Zn2+/Al3+/MTX摩尔比(R值)对合成MTX/LDHs复合物性质的影响.利用X-射线衍射(XRD)、傅里叶变换红外(FT-IR)、透射电子显微镜(TEM)、扫描电子显微镜(SEM)、原子力显微镜(AFM)和紫外-可见光谱(UV-Vis)等表征了复合物的结构和形貌.结果表明,粒子的尺寸随MTX加入量的增大而减小;粒子沿a-b轴方向的生长速率比沿c轴方向的生长速率快.在磷酸缓冲液中考察了插层药物的控释性能并进行了动力学拟合,结果表明,采用modified Freundlich模型和parabolic diffusion模型分段拟合可较好地描述样品的释药过程.最后,采用MTT法探究了插层药物对肺癌细胞A549增殖的抑制作用,研究表明,复合物粒径越小,MTX/LDHs对癌细胞增殖的抑制作用越大.     

不同溶剂对甲氨蝶呤/类水滑石复合物性质的影响

采用共沉淀法将甲氨蝶呤(MTX)插层组装到类水滑石(LDHs)层间,分别考察了不同溶剂(如:水、乙醇/水、聚乙二醇-400/水、聚乙二醇-4000/水)对合成的甲氨蝶呤/类水滑石(MTX/LDHs)纳米复合物性质的影响.利用透射电镜(TEM)和原子力显微镜(AFM)观察产物形貌,利用X-射线衍射(XRD)、傅里叶变换红外(FTIR)、热重/差式扫描量热(TG-DSC)和紫外光谱(UV-Vis)等表征手段,对纳米复合物的结构及热力学性质进行了系统的研究.在pH=7.4的磷酸盐缓冲溶液中测定不同时间点药物累积释放量,考察了不同溶剂中合成的MTX/LDHs纳米复合物的药物控释性能.结果表明,短链聚乙二醇的加入保证了纳米粒子的稳定生长,能有效控制产物形貌,合成出的产物呈规则的圆片状,单分散性好,药物缓释性能平稳,释放过程属于药物扩散控制过程.当聚乙二醇分子链过长时,由于其自身容易发生缠绕,反而不利于纳米粒子的生长.     

离子交换法合成MTX/LDHs复合物的研究及体外细胞实验的探索

研究了不同水热温度下合成的层状双金属氢氧化物(layered double hydroxides,LDHs)对离子交换法制备的MTX/LDHs纳米复合物的影响.并利用透射电镜(TEM)、X-射线衍射(XRD)、MTT等手段,对纳米复合物的结构及载药量、控释-缓释性、生物细胞活性母体等性质进行了系统研究.结果表明,不同LDHs母体对离子交换后复合物的形貌和性质起着至关重要的作用.在磷酸缓冲液中考察了MTX/LDHs纳米复合物的药物控释性能并进行了动力学拟合,结果表明,采用离子交换法制备MTX/LDHs纳米复合物的释药过程是Fick扩散控制的离子交换和粒内扩散过程.最后,采用MTT法探究了MTX/LDHs纳米复合物对肺癌细胞A549增殖的抑制作用,结果表明,复合物较纯的MTX具有更好的抑制癌细胞增殖的作用.     

羟基喜树碱-类水滑石纳米杂化的共组装制备及表征

采用共组装法在水溶液中制备羟基喜树碱(HCPT)-层状双金属氢氧化物(LDH)纳米杂化物.先利用微通道反应器通过共沉淀法制备了Zn₂Al-NO₃ LDH纳米片,然后与羧酸盐型HCPT在水介质中共组装,制备了HCPT插层LDH的纳米杂化物.利用酸处理,可将层间HCPT由非生物活性的羧酸盐型转化为生物活性的内酯型,这对高生物活性HCPT-LDH纳米杂化物的绿色制备具有重要意义.共组装法制备HCPT-LDH纳米杂化物,耗时短、载药量高、分散性好,且利用原料配比可方便地调控载药量. HCPT分子在LDH层间以其长轴倾斜于层板呈双层排列.所制备的HCPT-LDH纳米杂化物具有良好的药物缓释性能,颗粒内部扩散是药物释放过程的控速步骤.药物释放过程可用准二级动力学模型描述.可以用于构筑LDH基药物输送-控释体系.     

微乳液中单分散银纳米颗粒的制备及抗磨性能

采用水/液体石蜡/Span 80-Tween 80/正丁醇微乳液体系, 制备了具有良好单分散性的Ag纳米颗粒. 通过X射线粉末衍射仪、透射电子显微镜、傅立叶变换红外光谱仪和热分析仪表征了Ag纳米颗粒的结构、形貌、粒径大小及分布、表面键合性质和热性能. 结果表明, 所制备的Ag纳米颗粒具有立方晶型结构, m(Span 80)∶m(Tween 80)=7∶3时, 粒径分布呈单分散性, 平均粒径约为6 nm. 在四球长时抗磨损试验机上考察了分散于液体石蜡中Ag纳米颗粒的抗磨性能. 实验结果表明, Ag纳米颗粒具有良好的抗磨性, 且能显著提高基础油的承载能力.     

表面预处理对镁铝水滑石结构性质和缓释性能影响

以Mg-Al-NO3水滑石(LDHs)为载体,将5-氟尿嘧啶(5-FU)通过离子交换法插入其层间,得5-FU/LDHs缓释材料。并对水滑石表面进行弱酸预处理改性,利用XRD、FTIR、TG-DSC、SEM和零电荷点(pHPZC)等表征手段,考察酸预处理对水滑石表面化学性质及微观结构的影响。结果表明,5-FU/LDHs的层间距从0.858 nm扩大到1.064 nm,层间5-FU2阴离子与主体层板通过氢键与静电作用,以呈一定角度单层交替排列于层间。酸预处理的水滑石粒径变小,层板正电荷密度增大。5-FU的释放机理是物理扩散、离子交换和药物溶解等协同作用,酸预处理可提高水滑石的缓释性能和稳定性。     

甲氨蝶呤柱撑水滑石超分子结构层柱材料的插层组装

用共沉淀和离子交换法将抗肿瘤类药物甲氨蝶呤(MTX)插层组装到水滑石层间,制备了一种新型的结晶度高、晶相单一且MTX在层间有序排列的超分子结构的药物-无机复合层柱材料.用XRD、原子光谱、元素分析、FT/IR、SEM及TG-DSC分析表征了超分子结构层柱材料的结构,并给出其结构模型.     

布洛芬插层类水滑石/淀粉凝胶复合物的制备及缓释行为

为设计新型布洛芬缓释体系提供实验依据,以氯化镁、氯化铝、布洛芬(IBU)及淀粉等为原料,采取共沉淀-焙烧还原法及冷冻-解冻法,制备了层状双氢氧化物-布洛芬插层复合物(LDH-IBU)、淀粉凝胶-布洛芬复合物(淀粉凝胶-IBU)及层状双氢氧化物/淀粉凝胶-布洛芬插层复合物(LDH/淀粉凝胶-IBU)。 通过傅里叶红外光谱仪(FT-IR)、X射线衍射仪(XRD)表征了上述3种复合物的结构,并研究了它们在模拟人体环境条件下的缓释性能。 结果表明,3种复合物中的IBU在不同的缓释介质中都具有一定的缓释效果,复合物释放速率大小为:LDH/淀粉凝胶-IBU>LDH-IBU>淀粉凝胶-IBU;在pH值为6.6和7.4以及0.9%生理盐水3种缓冲介质中释放速率依次减小。 释放动力学均符合准一级动力学方程。     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

Selective syntheses of 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones via temperature-dependent Rh(II)-carbenoid-mediated 2H-azirine-ring expansion

The Rh(II)-catalyzed reaction of 2-carbonyl-substituted 2H-azirines with ethyl 2-cyano-2-diazoacetate or 2-diazo-3,3,3-trifluoropropionate provides an easy access to 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones. These compounds can be selectively prepared from the same starting material using temperature as the only varied parameter. The 2-azabuta-1,3-diene intermediate, a common precursor for both heterocyclic products, isomerizes into 2H-1,3-oxazine under kinetic control, while 1H-pyrrol-3(2H)-one is the sole product of the reaction at elevated temperatures. According to DFT-calculations a one-atom oxazine ring contraction involving ring-opening to a 2-azabuta-1,3-diene intermediate, followed by a 1,5- and 1,2-prototropic shift leads to the consecutive formation of imidoylketene and azomethine ylide, which then further undergo cyclization to the pyrrole derivative.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.