甲氨喋呤-乳糖酰基壳聚糖的制备及其体外实验

制备了不同乳糖酰基取代度的N-乳糖酰基壳聚糖(LCH), 并通过红外光谱(IR)及核磁共振氢谱(1H NMR)对其进行了结构表征. 体外放射性配基竞争结合实验结果显示, 当乳糖酰基取代度为15.5%~38.9%时, LCH对肝实质细胞膜表面去唾液酸糖蛋白受体(ASGPR)具有特异亲和性, 即具有潜在的肝靶向性. 将甲氨喋呤(MTX)与壳聚糖以酰胺键偶联, 制备MTX-壳聚糖(MTX-CH), 再与乳糖酸反应生成目标产物MTX-乳糖酰基壳聚糖(MTX-LCH), 并通过紫外分光光度法(UV)检测MTX的取代度为5.6%, 乳糖酰基取代度为33.8%. 溶解性实验结果显示, MTX-LCH溶于pH=1~14的水溶液; 体外释放实验结果表明, MTX-LCH性质稳定, 能明显延缓MTX的释放.     

壳聚糖基多功能纳米药物载体的体外研究

制备了一种壳聚糖基多功能纳米药物载体系统, 并探讨了其体外释药性质. 合成了甲氨蝶呤-壳聚糖偶联物(MTX-CS), 甲氨喋呤(MTX)的取代度为6.3%; MTX-CS具有两亲性, 在水性介质中能自组装形成纳米粒子, 平均粒径为(269.5±18.3) nm, zeta电位为(25.7±0.9) mV. MTX-CS纳米粒子能有效包载抗血管生成药Combretastatin A-4(CA-4), 当药物/载体材料投料比为1∶4 时, 载药量为15.7%, 包封率为62.8%. 体外释放实验结果显示, CA-4释放较快, MTX释放缓慢, 有利于发挥2种药物的协同抗肿瘤作用.     

In vitro Studies of Chitosan-based Muitifunctional Drug Delivery Nanosystem

制备了一种壳聚糖基多功能纳米药物载体系统,并探讨了其体外释药性质.合成了甲氨蝶呤-壳聚糖偶联物(MTX-CS),甲氨喋呤(MTX)的取代度为6.3％;MTX-CS具有两亲性,在水性介质中能自组装形成纳米粒子,平均粒径为(269.5±18.3) nm,zeta电位为(25.7±0.9) mV.MTX-CS纳米粒子能有效包载抗血管生成药Combretastatin A-4(CA-4),当药物/载体材料投料比为1∶4时,载药量为15.7％,包封率为62.8％.体外释放实验结果显示,CA-4释放较快,MTX释放缓慢,有利于发挥2种药物的协同抗肿瘤作用.     

差别性释放两种药物的层层组装聚合物膜

基于层层组装技术制备了能够差别性释放2种药物的聚合物复合膜.通过大分子前体药物透明质酸-阿霉素(HA-DOX)与壳聚糖(HACC)的层层组装以及膜内后扩散负载甲氨喋呤二钠盐(MTX)的方法,实现了DOX和MTX 2种药物分子在聚合物膜中的负载.DOX和MTX在癌变组织的酸性环境下具有差别性的释放动力学,MTX在24 h内快速释放,而DOX长效缓释达10 d.细胞实验结果表明,差别性释放的DOX和MTX可有效地抑制癌细胞的增殖.     

不同分子量N-琥珀酰壳聚糖的制备及其与K562肿瘤细胞间亲和性的初步探讨

用化学降解法制备不同分子量的壳聚糖 ,以其为原料合成了系列N 琥珀酰壳聚糖 ,然后用异硫氰酸荧光素进行荧光标记 ,再与K5 6 2肿瘤细胞共孵育 ,通过流式细胞仪检测细胞的荧光强度来确定不同分子量N 琥珀酰壳聚糖与K5 6 2肿瘤细胞间亲和性的强弱 ,为靶向抗肿瘤药物载体的研究提供初步的参考 .结果表明N 琥珀酰壳聚糖和K5 6 2肿瘤细胞间有较强的亲和性 ,随着分子量的增加 ,其亲和性逐渐减弱 .     

O-羧甲基-N-琥珀酰壳聚糖对Cu~(2+)的吸附研究

以壳聚糖为原料,先制备O-羧甲基壳聚糖,再与琥珀酸酐水溶剂反应合成出O-羧甲基-N-琥珀酰壳聚糖衍生物,采用1H-NMR、FT-IR和TG表征其结构。系统研究了O-羧甲基-N-琥珀酰壳聚糖对水溶液中Cu~(2+)的吸附性能,主要考察了溶液的p H值、温度、吸附时间等因素对吸附的影响及吸附热力学性能。结果表明,O-羧甲基-N-琥珀酰壳聚糖对Cu2+平衡吸附量达到133.5mg/g,动力学符合准二级动力学模型,对Cu~(2+)的吸附符合Freundlich等温吸附模型。红外表明,吸附主要依靠分子结构中的羧基和氨基。     

凝胶过滤色谱-多角度激光散射法测定琥珀酰明胶自由氨基修饰度

琥珀酰明胶作为血浆代用品的临床疗效与其分子量分布和修饰度密切相关。本研究利用高效凝胶过滤色谱-多角度激光散射法(HPSEC-MALLS)并结合2,4,6-三硝基苯磺酸(TNBS)衍生法,探索建立一种测定琥珀酰明胶修饰度的方法。实验利用TNBS将琥珀酰明胶衍生,通过HPSEC-MALLS测定琥珀酰明胶的分子量变化,计算出琥珀酰明胶的修饰度。实验以人血清白蛋白为模型进行了方法验证,结果表明:该方法能较好地表征人血清白蛋白在TNBS衍生过程中的分子量变化,实验值与根据其氨基酸组成计算值一致。实验在HPSEC-MALLS测定琥珀酰明胶及TNBS衍生后琥珀酰明胶分子量及分布的基础上,利用凝胶过滤色谱分子量-保留时间拟合曲线,计算得到琥珀酰明胶的自由氨基修饰度为38%。结果表明利用高效凝胶过滤色谱-多角度激光散射法结合2,4,6-三硝基苯磺酸衍生法测定琥珀酰明胶的修饰度是可行的。     

萘酰亚胺-多胺缀合物与DNA作用的光谱学研究

采用荧光方法研究了DNA与萘酰亚胺-多胺缀合物1-3的作用,并分析了缀合物1-3对DNA的嵌入作用.结果表明,萘酰亚胺-多胺缀合物对DNA有嵌入作用,是DNA嵌入剂.     

pH响应型苯硼酸酯缀合物的制备、表征和智能释放研究

以葡聚糖(Dextran)作为主链,将罗丹明B(Rh B,荧光智能释放药物模型/示踪显像)、3-羟基苯硼酸(PBA)酯化后,缀合到葡聚糖上,形成一种新型p H响应的高分子缀合物.由于该高分子缀合物中存在硼酸酯键,使得其负载模型药物到达肿瘤细胞的溶酶体之后释放出罗丹明B,不仅降低了药物毒性,还能够示踪药物的递送过程.体外模拟释放结果表明,缀合物在癌细胞的溶酶体/内涵体(p H 5)内能很好地释放出罗丹明B,而在药物输送过程(p H 7.4)中有很少的罗丹明B释放出来.另外,高分子载体葡聚糖的存在,使聚合物体现出良好的生物相溶性,从而减少了对正常组织的伤害,在抗癌药物的智能释放方面具有很好的应用前景.     

若干3d过渡金属的甲氨喋呤配合物

本文制得了甲氨喋呤与钒、锰、铁、钴、镍、铜和锌的配合物,除铁为氧桥双核型外,其余均为1:1单核配合物。通过热重、红外、磁化率、电子顺磁共振(对铜和钒酰)和Mossbauer谱(对铁)的表征,对它们的可能结构进行了讨论。     

HMTTeF-TCNQF4的电导与化学结合

用化学方法合成出HMTTeF-TCNQF₄,组成比为1.07:1,测定氮1s电子的X射线光电子能谱(XPS),得电荷转移量ρ_XPS=0.74;测定拉曼光谱,得ρ_Ram=0.75,HMTTeF分子只有失去中心共轭π电子的离子化,而无碲原子失去孤电子的离子化,在固体中存在的价态形式为:([HMTTEF]⁺_0.79+[HMTTeF]⁰_0.28·([TCNQF₄]^-_0.79+[TCNQF₄]⁰_0.21),这与该物质电导率较高的事实相符。     

Synthesis and characterization of two cyclic organosiloxanes by multinuclear NMR spectroscopy and X-ray crystallography

1,3-[2′,6′-Pyridinebis(methyleneoxy)]-1,3-bis(diphenyl)cyclodisiloxane (9) and 2,6-pyridinebis(1,1-diphenylethoxy)diphenylsilane (11) were obtained from 2,6-pyridinediol derivatives with dichlorodiphenylsilane. An N→Si interaction is present in 2,6-pyridinebis(1,1-diphenylethoxy)diphenylsilane, which also shows fluxional behavior. The activation energy of 13.2 kcal mol⁻¹ for 11 was obtained for the intramolecular exchange between the phenyl groups from a variable-temperature ¹H-NMR study. The compounds were characterized by ¹H-, ¹³C- and ²⁹Si-NMR and their structures were established by X-ray crystallographic studies.     

Reactivity of Organolithium Reagents to 2,3,4,5-Tetraphenylcyclopentadienone and Crystal Structures of Addition Products

The conjugate addition reactions of four organolithium reagents to 2,3,4,5-tetraphenylcyclopentadienone (tetracyclone) were investigated to reveal the reactivity of organolithium reagents to tetracyclone. The results show that 1,2-addition products 2,3,4,5-tetraphenyl-1-(2-thienyl)-2,4-cyclopentadien-1-ol(1), 1-n-butyl-2,3,4,5-tetraphenyl-2,4-cyclopentadien-1-ol(2) and 1,2,3,4,5-pentaphenyl-2,4-cyclopentadien-1-ol(3) were synthesized in excellent yields while tetracyclone reacted with 2-thienyllithium, n-butyllithium and phenyllithium, respectively. Interestingly, three 1,2-, 1,4- and 1,6-addition isomers 1-tert-butyl-2,3,4,5-tetraphenyl-2,4-cyclopentadien-1-ol(4), 4-tert-butyl-2,3,4,5-tetraphenyl-2-cyclopenten-l-one(5) and 2-tert-butyl-2,3,4,5-tetraphenyl-3-cyclopenten-l-one(6), were simultaneously obtained by the conjugate addition reaction of tert-butyllithium with larger steric hindrance to tetracyclone. Compounds 1-6 were characterized by ¹H and ¹³C NMR spectra, Fourier transform infrared(FTIR) spectra and mass spectra(MS). The crystal and molecular structures of compounds 1, 2 and isomers 5, 6 were determined by X-ray single crystal diffraction technique. The results imply that the steric hindrance of tert-butyllithium probably play a key role in controlling the conjugate addition reaction. The conjugate addition mechanism of organolithium reagents to tetracyclone was proposed.     

Novel indirect enzyme-linked immunosorbent assay (ELISA) method to detect Total E. coli in water environment

In order to establish ELISA (enzyme-linked immunosorbent assay) method to detect Total E. coli in water environment, E. coli multi-characters antigens in water environment were prepared according to the characters of kinds of E. coli serotypes, including antigen of whole cell, antigen of disrupted whole cell, somatic antigen, flagellar antigen and fimbrial antigen. Total E. coli polyclonal antibodies were obtained from the New Zealand rabbits immunized with these five antigens, respectively. Antibodies generated in this research are with high titers and good purity, can conjugate with antigens, specifically, stably and strongly. Indirect ELISA shows the titers of antibody of whole cell and antibody of disrupted whole cell are both over 1 × 10⁵. The cross-reactivity of the antibody is from 12 to 30% which indicate the specificity of the antibody against Total E. coli. Based on these antibodies, we established indirect ELISA method to detect Total E. coli in water environment. The matrix effects were studied and the results show that there is no significant influence by all the factors. The ELISA result shows that the detection limitation could be 10⁴ CFU (colony forming units) L⁻¹. The indirect ELISA method developed in this study is well suited for Total E. coli analysis in real water samples as a rapid screen method.     

烟酰胺腺嘌呤二核苷酸(NAD~+)类似物的合成及性质

合成了3种新型结构稳定的烟酰胺腺嘌呤二核苷酸(NAD~+)类似物并通过~1H NMR、~(13)C NMR、~(31)P NMR和HRMS进行了表征。NAD~+类似物经80℃加热24 h后,通过~1H NMR确认其结构稳定;通过循环伏安法(CV)测定了其电化学性质,表明其仍然具有良好的氧化还原性能。     

Ab initio study of the two competitive channels HO2 + H → H2 + O2 and HO2 + H → H2O + O

Saddle point geometries and barrier heights have been calculated for the H abstraction reaction HO₂(²A″)+H(²S) → H₂(¹Σ⁺_g)+O₂(³Σ⁻_g) and the concerted H approach-O removing reaction HO₂ (²A″)+H(²S) → H₂O(¹A₁)+O(³P) by using SDCI wavefunctions with a valence double-zeta plus polarization basis set. The saddle points are found to be of C_s symmetry and the barrier heights are respectively 5.3 and 19.8 kcal by including size consistent correction. Moreoever kinetic parameters have been evaluated within the framework of the TST theory. So activation energies and the rate constants are estimated to be respectively 2.3 kcal and 0.4×10⁹ ℓ mol⁻¹ s⁻¹ for the first reaction, 20.0 kcal and 5.4.10⁻⁵ ℓ mol⁻¹ s⁻¹ for the second. Comparison of these results with experimental determinations shows that hydrogen abstraction on HO₂ is an efficient mechanism for the formation of H₂ + O₂, while the concerted mechanism envisaged for the formation of H₂O + O is highly unlikely.     

α－酰氨基环十二酮的合成及其结构表征

以易得的环十二酮为原料,制得中间体α-硝基环十二酮后,选择性还原为α-氨基环十二酮(Ⅱ),再经氨基的酰化,共合成12种目标化合物(Ⅲ).它们的结构用IR,MS,¹H NMR和元素分析进行了表征。初步的生物测定表明,它们中的一些对稗草和油菜显示出良好的除草活性。在合成Ⅱ的过程中,分离到一种结晶化合物,经波谱测定和元素分析确定其结构为双[邻-1,10-亚癸基]吡嗪(Ⅳ),并得到合成的验证。     

2D NMR Studies on the Structure of Urushiol of Chinese Lacquer

The urushiol diacetate was successfully separated by centrifugal rotation TLC on the silica gel coated with silver nitrate.The structure and configuration of key component of.urushiol (64.6%) were determined successfully by using 1H and 13C conventional method,DEPT technique,homo- and heteronuclear chemical shift correlation 2D-NMR,2D-J NMR,hftteronuclear relayed coherencetransfer 2D-NMR,and relaxation time T1 investigation.The as-signment of resonances for 1H and C were confirmed.There is plentyof evidence which shows that the key component of urushiol is3-(8'Z,11'E,13'Z-pentadecatrienyl)catechol.The results show that RELAY 2D-NMR new technique can be successfully applied to determining the structure of complicated unknown compounds.     

气相中碱金属离子与丝氨酸、 亮氨酸和赖氨酸五肽复合物的裂解反应

为了探索金属离子对含有不同侧链的多肽气相解离的影响, 采用质谱法研究了碱金属离子Li⁺, Na⁺, K⁺, Rb⁺和Cs⁺分别与丝氨酸、 亮氨酸和赖氨酸五肽(分别简写为S5, L5和K5)形成的复合物的裂解反应. 质谱定性结果表明, 5种碱金属离子均可以在气相中与丝氨酸、 亮氨酸和赖氨酸五肽形成配合比为1∶1 和2∶1的非共价复合物; 竞争反应结果表明, 随着碱金属离子半径的增加, 它们与3种五肽的结合能力逐渐减弱. 质谱定量结果表明, K⁺与丝氨酸、 亮氨酸和赖氨酸五肽复合物的结合常数分别为8.94×10⁴, 2.83×10⁴和2.50×10³ L/mol, 表明K⁺与五肽复合物的结合强度按照丝氨酸、 亮氨酸和赖氨酸的顺序依次减小. 含不同侧链碱金属离子-五肽复合物的碰撞诱导解离结果表明, 复合物的碎裂主要发生在骨架上, 丝氨酸五肽复合物最易碎裂, 亮氨酸五肽复合物其次, 赖氨酸五肽复合物则较难碎裂, 且3种复合物的侧链断裂情况也呈现明显差异. 此外, 研究了Na⁺与亮氨酸五肽复合物所产生的碎片离子, 分析了不同离子之间的来源关系, 并以Dunbar的复合物理论模型为依据, 推测在碎裂过程中, 碱金属离子可能向五肽的碳端或氮端偏移. 质谱碎片分析结果表明, 在2∶1的非共价复合物中, 第一个碱金属离子与五肽上4个酰胺键的羰基结合, 第二个碱金属离子与五肽的羧基氧原子结合.     

Preparation and Luminescence Behavior of CaSiO3：Eu^3＋（Bi^3＋）

CaSiO3：Eu0.08^3＋Bi0.002^3＋ with a monoclinic perovskite structure was synthesized by using sol-gel method, and its luminescence characteristics were investigated. From the excitation spectrum, it can be seen that the main peaks located at 238,396,415,437 and 359 nm correspond to the charge-transfer band of Eu^3＋-O^2- , the absorption transitions of ^7F0.1→^3L6, ^7F0→^5D3, ^7F1→^5D3 of Eu^3＋ ions, and ^3P1→^1S0 of Bi^3＋ ions, respectively. When the samples were excited with a light of wavelength 359 or 395 nm, it can be seen from the emission spectrum that the electronic dipole transition located at 609 nm corresponding to ^5D0→^7F2 of Eu^3＋ ions was stronger than the magnetic dipole transition located at 587 nm corresponding to ^5D0→^7F1 of Eu^3＋ ions, which shows that more Eu^3＋ ions were located in nonreversion center lattices. The energy transfer from Bi^3＋ ions to Eu^3＋ ions in the phosphor was also discussed. The results show that Eu^3＋ ions could be well sensitized by ^3＋ions, and the energy-transfer pattern between Bi^3＋ ions and Eu^3＋ ions was resonance energy transfer.