胆固醇修饰富勒烯/γ-环糊精包结复合物的生物活性

采用Bingel-Hirsch反应合成了胆固醇修饰的富勒烯(CHL-C60),通过核磁共振(NMR)、质谱(MS)、元素分析对CHL-C60的化学结构进行了表征.γ-环糊精(γ-CD)对甾环具有较强的包结能力,能够与CHL-C60形成包结复合物(CHL-C60/γ-CD),从而有效提高CHL-C60的水溶性.紫外-可见吸收光谱和荧光光谱研究结果表明,CHL-C60能够从γ-CD的疏水空腔中解离出来,与人血清白蛋白(HSA)及牛血清白蛋白(BSA)形成稳定的复合体,其结合常数分别为5.73×104和7.05×104L.moL-1.无氧条件下,CHL-C60/γ-CD通过光诱导电子转移作用断裂pBR322质粒脱氧核糖核酸(DNA),其效率可达60.5%.     

桥联双β-环糊精对N-[4-(1-芘基)]丁酰-D/L-苯丙氨酸的手性识别及机理研究

利用紫外-可见吸收和荧光发射光谱, 结合非线性最小二乘法拟合曲线以及分子力学(MM2)模拟系统地研究了手性分子N-[4-(1-芘基)]丁酰-D/L-苯丙氨酸(PDP和PLP, 总称PPs)与β-环糊精(β-CD)、 2-位硒桥联双β-CD(2-SeCD)和2-位碲桥联双β-CD(2-TeCD)的包结能力大小及这3个环糊精对PPs手性识别能力的差异和识别机理. 研究结果表明, PPs不能与单疏水空腔的β-CD形成很好的包结复合物, 与具有较长桥联链的2-TeCD结合能力最强. 2-TeCD与PDP和PLP的结合常数分别为2.33×104和6.07×103 L/mol, 对PPs的手性识别比达到KD/KL=3.84, 高于2-SeCD(KD/KL=2.61). 用MM2模拟得出了PPs与这两个双环糊精形成复合物的三维结构: PPs的绝大部分位于双环糊精两个空腔之间, 但是在这两个复合物中, 苯环与芘环所成的二面角不同. 此外, PPs与这两个双环糊精作用时均存在明显的氢键相互作用, 且2-TeCD强于2-SeCD.     

环丙沙星与环糊精超分子体系的研究

利用荧光光谱法研究了环丙沙星与母体β-环糊精(β-CD)及其2种修饰衍生物羟丙基-β-环糊精(Hp-β-CD)、甲基-β-环糊精(Me-β-CD)形成的超分子体系,同时测定了3种超分子体系的猝灭常数和热力学参数.结果表明:环丙沙星与3种环糊精之间常温下均形成稳定的包合物;环丙沙星与3种环糊精包结过程中△G＜0和△H＜0,这说明环丙沙星与3种环糊精的包结能够自发进行而形成超分子体系,且反应为放热过程.通过对3种环糊精与环丙沙星的热力学数包结能力进行了比较,初步探讨了作用机理和影响包结能力大小的可能因素.     

5-邻硝基苯-10,15,20-三苯基卟啉-环糊精超分子体系研究

在中性磷酸盐缓冲溶液中,以紫外-可见分光光度法、荧光光谱法和1HNMR法研究了一种人工合成的非水溶性卟啉5-邻硝基苯-10,15,20-三苯基卟啉(简称o-NTPP)与3种母体环糊精α-CD、β-CD、γ-CD和β-CD的两种衍生物2,3,6-三-甲氧基-β-CD(TM-β-CD)、羧甲基-β-CD(CM-β-CD)之间相互作用形成的超分子体系,结果表明o-NTPP与TM-β-CD形成了1∶2的包结物,而与其它4种环糊精均形成1∶1的包结物。利用双倒数曲线法计算了o-NTPP-CD超分子体系的包结常数(k),同时对包结常数大小进行了比较,从而判断出5种环糊精对o-NTPP包结能力的大小,其中TM-β-CD表现出最强的包结能力。     

β-环糊精对丁吡吗啉的包合作用

采用紫外光谱定量研究了β-环糊精(β-CD)对新型杀菌剂丁吡吗啉的包结行为, 结果表明, β-CD与丁吡吗啉形成包结比为1∶1的包结物, 其包结常数随温度升高而减小, 表明包结是一个放热过程; 包结反应热力学参数ΔH, ΔS和ΔG均为负值, 说明包结反应是焓变驱动的自发过程.相溶解度实验表明, β-CD能显著提高丁吡吗啉在水中的溶解度, 有助于该产品剂型的水基化, 且包合对其杀菌活性没有明显影响. 对固态包结物的IR和2D ROESY分析表征表明, 丁吡吗啉以其苯环端从β-CD的窄端进入其空腔, 叔丁基进入到β-CD的阔端, 而分子中的其它部分位于空腔的窄端外.     

BATPPH_2及其Zn配合物与环糊精的超分子体系研究

设计合成了5-(4-苯甲酰亚胺基苯基)-10,15,20-三苯基卟啉(BATPPH2)及其锌配合物(BATPPZn),并通过1HNMR、IR、UV-Vis、元素分析等方法对化合物的结构加以确认。在中性磷酸盐缓冲溶液中,以荧光光谱法、紫外可见分光光度法和1HNMR法分别研究了BATPPH2和BATPPZn与α,β,γ-环糊精相互作用形成的超分子体系。利用双倒数曲线法计算了BATPPH2-CD和BATPPZn-CD超分子体系的包结常数,结果表明BATPPH2和BATPPZn与γ-CD的包结常数(K1γ-CD,K2γ-CD)最大,γ-CD表现出最强的包结能力,Zn2+的配位作用使包结物的稳定性降低。     

β-环糊精和甾类化合物的分子动力学模拟

运用分子动力学(molecular dynamics, MD)和MM-PBSA (molecular mechanics/Poisson Boltzmann surface area)相结合的方法预测了β-环糊精(cyclodextrin, CD)和甾类客体分子包结模式. 通过重原子均方根偏差(root mean square deviation, RMSD)分析可得, 两种包结模式下客体分子都可以和β-CD形成稳定的包结. 在MD轨迹采样基础上, 采用高效MM-PBSA方法计算了两种包结模式下的包结自由能. 计算结果显示, β-CD和三个甾类客体分子包结的主要驱动力为范德华相互作用, 而溶剂化能和熵变则不利于体系的包结. 进一步分析平均构象和包结自由能发现, 对于波尼松龙, D-up (D-ring up orientation)取向为优势包结模式; 而乙炔雌二醇和雌三醇的优势包结模式均为A-up (A-ring up orientation)取向. 通过比较β-CD和三个客体分子的理论包结自由能, 预测包结稳定性的次序为乙炔雌二醇＞雌三醇＞波尼松龙, 和实验结果相一致.     

疏水-亲脂作用对反应性的影响III:环糊精对碳氟表面活性剂的熵驱动包结以及亲脂作用对形成糖淀粉型包结物的贡献

用表面张力-浓度曲线法系统地研究了环糊精(CD)和羧甲基糖淀粉钠(Na-CMA)与H(CF2)12CO2K(1),Cl(CF2)nCH2CH2N^+(CH3)3I^-[n=8(3),10(5)]和相应的碳氢表面活性剂(2,4和6)的相互作用.由于几何尺寸的限制,碳氟表面活性剂不能与α-CD形成包结络合物,但3与β-CD形成的包结络合物的稳定性远大于相应的碳氢受物4、3与β-CD的相互作用是熵驱动过程,而C12H25N^+(CH3)3I^-(6)则是焓有利的.与具有"预组织化"内穴的CD不同,糖淀粉的包结是与大分子从线团到螺旋构象变化的协同过程,由于缺乏宿主-受物间的亲脂相互作用,Na-CMA不能与所有的碳氟受物形成包结络合物.     

阿托伐他汀钙与β-环糊精相互作用的研究及应用

采用线性扫描伏安法和循环伏安法并结合紫外分光光度法研究了新型抗血脂紊乱药物阿托伐他汀钙(AC)与β-环糊精(-βCD)的相互作用.探讨了-βCD对AC的峰电流及AC对-βCD吸附峰电流的影响,测得在0.06mol/LKH2PO4-Na2HPO4(pH=7.17)缓冲溶液中,AC与-βCD包结比为1:1,用电流法测得包结物的形成常数为9.09×104L/mol.根据碱性介质条件下β-CD分子与AC形成包结物而使β-CD吸附峰电流减小的特性,建立了一种利用β-CD间接测定AC的伏安方法.     

β-环糊精与Triton N-101相互作用的研究

用表面张力法及紫外光谱研究了β-CD与非离子型表面活性剂Triton N-101(TN)的包结体系.结果表明, TN的表面张力值及表观临界胶束浓度(CMC*)随β-CD浓度增加而增大,由于实验数据与所构建的1∶ 1包结的数学模型完全相符,由此推测β-CD与TN形成1∶ 1包结物.运用这一数学模型计算了TN与β-CD体系的包结平衡常数Ka(298 K),结果表明Ka值与β-CD浓度成正比.通过Ka值还计算了包结体系自由能变化.紫外光谱结果表明,在β-CD浓度较小时, TN 的疏水链优先进入β-CD内腔,而β-CD浓度较大时, TN 的苯环部分也进入β-CD内腔.     

抗抑郁化合物SIPI5358与环糊精形成的非共价复合物

用电喷雾电离质谱(ESI-MS)和串级质谱(MS/MS),并结合紫外光谱、荧光光谱等方法,研究一种芳烷醇哌嗪类抗抑郁化合物SIPI5358与α-、β-、γ-环糊精(CD)制备得到的非共价复合物.质谱分析结果显示,SIPI5358分子可以和α-CD生成配合比为1∶1的非共价复合物,而与β-、γ-CD生成不同配合比的非共价复合物.串级质谱的结果进一步验证β-CD与SIPI5358非共价复合物的组成.用紫外光谱和荧光光谱实验对液相中非共价复合物的形成进行了辅助研究,结果均再次验证了非共价复合物的生成.荧光光谱实验测得SIPI5358与β-CD反应的生成常数Kf=3.45×103 mol.L-1.     

α-环糊精修饰有机聚合物整体材料选择性富集室温磷光法测定土壤中的萘

合成了α-环糊精（α-CD）修饰的有机聚合整体材料,对合成的材料进行了表征,研究比较了α-CD修饰整体材料作为室温磷光固体基质的效果以及14种有机化合物在其上的室温磷光分析(RTP)行为。 α-CD修饰的有机聚合整体材料背景干扰低, 对二环芳烃类物质有较好的选择性和富集能力。 在α-CD修饰膜上,萘和7,8苯并喹啉的分配常数分别为5.03×103和2.94×102,表明修饰材料对萘有较好的选择性。 萘酚也能与修饰材料形成包络物。 但是由于较强的极性和在水中的溶解性,不能被有效富集。 对5.0×10-11 mol/mL萘,最大富集体积为300 mL。 采用SPE-RTP,萘和7,8苯并喹啉的检出限分别为9.80×10-12和4.60×10-11 mol/mL,RSD小于3.7%;线性范围分别为5.00×10-11~8.00×10-9 mol/mL和6.00×10-11~5.00×10-10 mol/mL。 应用修饰的膜片对土样中的萘进行选择性富集和测定,结果由GC-MS进一步确认。 用环己烷一步提取和SPE-RTP测定,萘可以被选择性富集。 在土壤样品中加萘标准0.012 8 mg,测得回收率（104.9±6.5）%。 土样中萘的浓度为（5.61±0.12） mg/kg,与GC-MS的较为吻合。     

Investigation on the interaction of tetrachloride fluorescein-bovine serum albumin-beta-cyclodextrin and the determination of protein by flow injection analysis

In this paper, a simple and sensitive flow injection analysis (FIA) for the determination of protein with spectroscopic probe was developed. This method was based on the investigation of the interaction of tetrachloride fluorescein (2,4,5,7-tetrachloro-3,6-fluorandiol)-bovine serum albumin (BSA), the coupling reaction of protein with tetrachloride fluorescein (TCFS) which was used as a spectroscopic probe in the presence of β-cyclodextrin (β-CD). The interaction mechanism and the main factors affecting the determination were investigated in details. Under the optimum conditions, the linear range and detection limit were 0.0-28.0 μg mL⁻¹ and 0.76 μg mL⁻¹, respectively. The proposed method has been used to determine albumin in serum albumin with satisfactory results.     

Spectrophotometric investigation on the interaction of toluidine blue with calf thymus DNA by cyclodextrin supramolecular

The interaction of toluidine blue (TB) with cyclodextrins (CDs), including β-cyclodextrin (β-CD) and carboxymethyl-β-cyclodextrin (CM-β-CD), and calf thymus DNA in aqueous solution is studied by ultraviolet-visible absorption and steady-state fluorescence technique. The interactive model of TB with double-stranded DNA has been investigated by means of the inclusive action of β-CD and CM-β-CD. Based on the changes of absorption, fluorescence and resonance light scattering (RLS) spectra, the intrinsic binding constant (K_ap) and the binding site number (n) of TB with DNA and the inclusion complexes TB–CD with DNA are obtained in the case of 20 mmol L^?1 Tris-HCl buffer solution (pH 7.2). According to the experimental results, it can be inferred that the interactive model of dimer TB with DNA is ‘electrostatic binding’, while the monomer TB with DNA is ‘intercalative binding’.     

Host–guest complexation of a nitroheterocyclic compound with cyclodextrins: a spectrofluorimetric and molecular modeling study

Nitroheterocyclic compounds (NC) were candidate drugs proposed for Chagas disease chemotherapy. In this study, we investigated the complexation of hydroxymethylnitrofurazone (NFOH), a potential antichagasic compound, with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), Hydroxypropyl-β-cyclodextrin (HP-β-CD), Dimethyl-β-cyclodextrin (DM-β-CD) and γ-cyclodextrin (γ-CD) by fluorescence spectroscopy and molecular modeling studies. Hildebrand–Benesi equation was used to calculate the formation constants of NFOH with cyclodextrins based on the fluorescence differences in the CDs solution. The complexing capacity of NFOH with different CDs was compared through the results of association constant according to the following order: DM-β-CD > β-CD > α-CD > HP-β-CD > γ-CD. Molecular modeling studies give support for the experimental assignments, in favor of the formation of an inclusion complex between cyclodextrins with NFOH. This is an important study to investigate the effects of different kinds of cyclodextrins on the inclusion complex formation with NFOH and to better characterize a potential formulations to be used as therapeutic options for the oral treatment of Chagas disease.     

TICT荧光探针法研究甲基化的β-环糊精空腔微环境

p-dimethylaminobenzonitrile (DMABN), a typical dual fluorescent flurophore (TICT flurophore), was used as fluorescent probe. The microenviromental property of twelve methyl modified β-cyclodextrin(methyl β-CD) was compared with that of β-cyclodextrin (β-CD). Results showed that the polarity of the cavity of methyl β-CD is lower than that of β- CD, and the capacity of methyl β-CD inclusion with DMABN is stronger than that of β-CD inclusion with DMABN.     

Evidence of changes in hydrophilic/hydrophobic balance and in chemical activity of HSA induced by thermal treatments

Samples of human serum albumin (HSA) obtained as a result of heat denaturation followed by refolding controlled by a cooling of the protein solution were studied by several methods: chromatographic measurements, kinetic of the reaction with a water soluble free radical and by electron paramagnetic resonance (EPR) spectroscopy. In this context the interaction of this protein with β-cyclodextrin (β-CD) and sodium dodecyl sulfate (SDS) was also investigated. Reversed phase thin layer chromatography (RP-TLC) showed changes in lipophylicity of HSA, which are related with the existence of different ensembles of conformers. The UV-Vis absorption spectra had shown the broadening of absorption band of the protein and a hyperchrom effect in the presence of SDS; β-CD reduces the effect of SDS on protein UV-Vis spectra.