米托蒽醌分子印迹传感器的研究及其应用

在弱酸性条件下, 以邻氨基酚为单体交联剂, 米托蒽醌为模板分子, 用循环伏安法电聚合成米托蒽醌分子印迹聚邻氨基酚敏感膜传感器. 该传感器对米托蒽醌具有良好的选择性和敏感度, 米托蒽醌浓度分别在3.3×10-7~1.0×10-5 mol/L及1.0×10-5~5.0×10-5 mol/L范围内与峰电流减小量呈线性关系, 检测下限为1.6×10-7 mol/L, 同时对分子印迹膜的结构和性能进行了研究.     

米托蒽醌分子印迹聚邻氨基酚敏感膜传感器的研制

在弱酸性条件下,在金电极上以邻氨基酚为单体和交联剂,米托蒽醌为模板分子,用循环伏安法电聚合成米托蒽醌分子印迹聚邻氨基酚敏感膜传感器。该传感器对米托蒽醌具有良好的选择性和敏感度,米托蒽醌浓度分别在2.0×10^-7—1.0×10^-5mol／L及1.0×10^-5—5.0×10^-5mol／L范围内与峰电流减小量呈线性关系,检出限为1.2×10^-7mol／L。本文同时对分子印迹膜的结构和性能进行了探讨与研究。     

米托葸醌分子印迹传感器的研究及其应用

在弱酸性条件下,以邻氨基酚为单体交联剂,米托蒽醌为模板分子,用循环伏安法电聚合成米托蒽醌分子印迹聚邻氨基酚敏感膜传感器。该传感器对米托蒽醌具有良好的选择性和敏感度,米托蒽醌浓度分别在3．3×10^-7～1．0×10^-5moL／L及1．0×10^-5～5．0×10^-5moL／L范围内与峰电流减小量呈线性关系,检测下限为1．6×10^-7moL／L,同时对分子印迹膜的结构和性能进行了研究。     

镍离子注入修饰电极上米托蒽醌与DNA相互作用的电化学研究

研究了在镍离子注入修饰电极和0.05mol/LTris-0.5mol/LNaCl缓冲溶液(pH=7.1)中,米托蒽醌(MX)与DNA作用的电化学.在37℃恒温1.5h条件下,MX与DNA形成一种非电活性的结合物,使MX峰电流降低,其结合比n(MX):n(DNA)=2:1,结合常数为1.61×10¹²,电子转移系数为0.41,电极反应速率常数0.33s^-1.加入DNA后,MX峰电流降低,据此,可以测定DNA.     

米托蒽醌的吸附行为及其吸附伏安测定法研究

本文研究了米托蒽醌在悬汞电极上的吸附行为，在此基础上建立了米托蒽醌的吸附伏安测定方法。在ｐＨ为２．２的Ｂ．Ｒ缓冲体系中，米托蒽醌浓度在１．１×１０＾－６ｍｏｌ／Ｌ～１．１×１０＾－９ｍｏｌ／Ｌ范围内，浓度与电流呈线性，检出限可达５．５×１０＾－１０ｍｏｌ／Ｌ。若在盐酸－柠檬酸钠（ｐＨ为１．２５）缓冲体系中，检出限可低至１．１×１０＾－１１２ｍｏｌ／Ｌ。方法可用于尿样或血样中米托蒽醌的测定。     

溴化乙锭对B-DNA碱基对特异性识别的分子模拟研究

溴化乙锭是一种常用的DNA荧光探针, 其作用机制是通过插入作用与DNA分子形成稳定的复合物. 分子模拟显示, 溴化乙锭插入碱基对过程中有大小沟选择性, 对结合能的统计分析发现, 溴化乙锭分子更倾向从小沟方向插入到DNA分子中. 由溴化乙锭从小沟方向插入不同碱基对的结合能考察发现, 溴化乙锭对DNA碱基对有特异性识别, 并且与CA碱基对结合能最强. 对溴化乙锭插入DNA分子的驱动力和序列特异性识别的作用力分析, 揭示溴化乙锭插入DNA分子的驱动力和碱基对的特异性识别均以静电作用为主.     

米托蒽醌与生物大分子DNA结合平衡的研究

米托蒽醌(MX)是一个广谱高效的葸醌类抗癌新药(下式),核酸是该类药物的主要细胞作用靶位,它通过与DNA结合,影响DNA的转译和复制,从而起到抗癌作用。研究这类药物与核酸的作用对于阐明抗癌机理具有重要意义,为此,广泛地开展了这方面的研究。     

不可逆电活性药物米托蒽醌与脱氧核糖核酸的相互作用

研究了抗癌新药米托蒽醌(MXT)的电化学行为及与脱氧核糖核酸(DNA)的相互作用，推导了适用于研究不可逆电活性分子与DNA相互作用的电化学公式，运用该公式可以简便、快速地测定靶向分子与DNA的结合常数和结合位点数。实验发现，MXT与小牛胸腺DNA的结合以蒽醌母核的嵌插作用为主，同时，烃氨基侧链与骨架磷酸基团之间的静电吸引对母核起稳定作用，使化合物易于嵌入DNA的平面结构。MXT与DNA相互作用引起的峰电流的变化可以用于分析测定DNA。     

米托蒽醌在金电极上的电化学研究及其应用

米托蒽醌(MTX)在0.2 mol/L B-R缓冲溶液(pH=1.5)中循环伏安扫描时,在金电极上会产生一个灵敏的氧化峰P1(峰电位为1.087 V)和两个灵敏的还原峰P2(峰电位为0.817 V)、P3(峰电位为0.764 V)。P1峰电流值与MTX浓度在1.0×10-9~1.0×10-6mol/L范围内呈良好的线性关系;其检出限可达5.6×10-10mol/L。本研究优化了测定米托蒽醌的最佳实验条件,建立了可灵敏测定米托蒽醌的新方法;同时对米托蒽醌在金电极上的电化学行为进行了较为详细的研究。     

Molecular modeling of the binding mode of chiral metal complexes △- and (A)-[Co(phen)2dppz]3+ with B-DNA

Molecular modeling methods have been applied to the structural characterization of the interaction between chiral metal complexes [Co(phen)2dppz]3+ (where phen = 1, 10-phenanthroline, dppz = dipyrido[3,2-a: 2′, 3′-c]phenazine) and the oligonucleotide (B-DNA fragment). The natures of two kinds of the binding modes, which are currently intense controversy, have been explored. Barton proposed that there is enantio-selective DNA binding by the octahedral complexes and intercalative access by these complexes from the major groove; but Norden suggested that both enantiomers bind extremely strongly to DNA from the minor groove without any noticeable enantio-selectivity. Our results support and extend structural models based upon Norden's studies, and conflict with Barton's model.     

Molecular modeling of the binding mode of chiral metal complexes A- and A-[Co(phen)_2dppz]~(3 ) with B-DNA

Molecular modeling methods have been applied to the structural characterization of the interaction between chiral metal complexes [Co(phen)2dppz]3 (where phen = 1, 10-phenanthroline, dppz = dipyrido[3,2-a: 2', 3'-c]phenazine) and the oligonucleotide (B-DNA fragment). The natures of two kinds of the binding modes, which are currently intense controversy, have been explored. Barton proposed that there is enantio-selective DMA binding by the octahedral complexes and intercalative access by these complexes from the major groove; but Norden suggested that both enantiomers bind extremely strongly to DNA from the minor groove without any noticeable enantio-selectivity. Our results support and extend structural models based upon Norden's studies, and conflict with Barton's model.     

化学及生物体系中的分别识别*

分子识别的目标是研究分子间专一性地相互作用, 这在化学及生命过程中起着非常重要的作用。本文综述了分子识别的机制及其在化学、生命科学、材料、信息等有关学科中的应用。     

光谱法结合分子模拟分析乳铁蛋白与药物恩诺沙星的互作分子机理

利用光谱实验结合计算机模拟技术研究了药物恩诺沙星(Enrofloxacin,EFLX)与牛乳铁蛋白(Bovine lactoferrin,BLF)的相互作用机理。测定反应体系的结合参数、能量转移参数及热力学函数,考察EFLX对BLF分子构象的影响,并模拟EFLX-BLF结合反应的分子模型。结果表明,药物分子与牛乳铁蛋白的相互作用表现为动态结合过程,结合强度适中,EFLX与BLF分子的结合距离r值较小,说明发生了能量转移现象。EFLX影响BLF的结构域微区构象,降低结合位域的疏水性。荧光相图技术解析出EFLX与BLF反应构象型态的变迁为"二态模型"。EFLX-BLF的热力学参数表明两者间是以氢键和范德华力为主的分子间作用。分子建模结果显示,EFLX与BLF的相互作用主要为氢键和范德华力,兼有疏水作用力。计算机分子模拟与实验测试获得了一致性结果。     

光谱法与分子模拟技术研究杨梅素与牛血清白蛋白的相互作用

利用紫外光谱、荧光光谱、红边激发荧光位移(REES)法、圆二色谱(CD)结合分子模拟技术共同研究了模拟生理条件下杨梅素与牛血清白蛋白(BSA)的相互作用,阐述了相互作用机制.分子模拟结果表明,杨梅素与蛋白在亚结构域II A的疏水腔内结合,主要作用力为疏水作用力和氢键.依据荧光猝灭法判断猝灭机制为静态猝灭,并得到不同温度下药物与蛋白相互作用的结合常数(Ka)及结合位点数(n),根据热力学参数判断出作用力类型,并且计算出杨梅素与蛋白的结合距离,与分子模拟得到的判定结果基本一致.通过紫外光谱、同步荧光光谱以及REES法获得的信息讨论了相互作用时BSA中色氨酸(Trp)微环境的变化;并利用CD谱的测定结果定量计算了BSA二级结构中α-螺旋含量的变化.     

腺苷与人血清白蛋白间相互作用的荧光光谱及分子模型法研究

在模拟人体生理条件下,结合紫外光谱和分子对接模型运用荧光光谱研究了腺苷与人血清白蛋白(HSA)间的键合作用。腺苷有较强的能力猝灭人血清白蛋白的内源荧光,且根据Stern-Volmer方程判断出猝灭机制为静态猝灭。本文运用相应的荧光值和Vant’Hoff热力学方程求得了不同温度下的结合常数(K)以及一些热力学参数,如焓变(ΔH)和熵变(ΔS)。结果表明：键合过程中疏水作用力对新化合物的稳定性起主要作用,这与分子对接模型方法研究的结果基本一致。另外还研究了常见离子对结合常数的影响。     

光谱法及分子模拟研究芹菜素与人血清白蛋白的相互作用

利用紫外光谱、荧光光谱、红外光谱、圆二色光谱及分子模型等技术,在生理pH条件下,研究了芹菜素与人血清白蛋白的相互作用,计算了结合常数和热力学参数。分子模型研究表明,芹菜素与人血清白蛋白在亚结构域ⅡA结合,二者间的主要作用为疏水作用和静电作用,这与荧光光谱所得结果基本一致。红外光谱、圆二色光谱及同步荧光光谱均显示芹菜素与人血清白蛋白结合后没有改变人血清白蛋白的二级结构。     

Interaction of Valdecoxib with β-cyclodextrin: Experimental and Molecular Modeling Studies

This study aimed to investigate the effect of β-cyclodextrin on aqueous solubility and dissolution rate of valdecoxib and also to get an insight of molecular interactions involved in formation of valdecoxib‐β-cyclodextrin inclusion complex. Phase solubility analysis indicated complex with possible stoichiometry of 1:1 and a stability constant of 234.01 M⁻¹. Thermodynamic studies in water indicated exothermic nature of inclusion complexation.␣Valdecoxib‐β-cyclodextrin complexes (1:1 M) were prepared by kneading method, solution method and␣freeze–drying method. The complex was characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (P-XRD), Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance␣(¹H-NMR) spectroscopy. Molecular modeling was used to help establish the mode of interaction of β-cyclodextrin with valdecoxib. ¹H-NMR analysis suggested that the unsubstituted phenyl ring of valdecoxib display favorable interaction with the hydrophobic cavity of β-cyclodextrin, which was confirmed by molecular dynamic simulations. An inclusion complex model has been established for explaining the observed enhancement of solubility of valdecoxib in water by β-cyclodextrin. Dissolution studies in water showed that the valdecoxib in freeze-dried complex dissolved much faster than the uncomplexed drug and physical mixture. This improvement in dissolution rate is attributed to the increased solubility and wettability due to encapsulation along with decreased crystallanity caused by complex formation, which is evident by DSC and P-XRD studies.     

光谱法与分子模拟技术研究丽春红2R与牛血清蛋白的相互作用

采用荧光光谱、同步荧光光谱、紫外-可见吸收光谱及分子模拟技术研究了模拟生理条件下丽春红2R(P2R)与牛血清白蛋白(BSA)的相互作用。实验结果表明,P2R-BSA体系的荧光猝灭机制为内源荧光猝灭,猝灭原因为静态猝灭和非辐射能量转移;计算了不同温度下体系的结合常数Ka及结合位点数n;根据热力学参数推断出作用力类型;求出室温下荧光给体-受体间的结合距离;同步荧光法证实丽春红2R对BSA构象未产生影响;分子模拟研究结果表明二者间的主要作用力为氢键和疏水作用力。     

Molecular Modeling of the Three‐Dimensional Structure of Human Sphingomyelin Synthase

Sphingomyelin synthase (SMS) produces sphingomyelin and diacylglycerol from ceramide and phosphatidylcholine. It plays an important role in cell survival and apoptosis, inflammation, and lipid homeostasis, and therefore has been noticed in recent years as a novel potential drug target. In this study, we combined homology modeling, molecular docking, molecular dynamics simulation, and normal mode analysis to derive a three‐dimensional structure of human sphingomyelin synthase (hSMS1) in complex with sphingomyelin. Our model provides a reasonable explanation on the catalytic mechanism of hSMS1. It can also explain the high selectivity of hSMS1 towards phosphocholine and sphingomyelin as well as some other known experimental results about hSMS1. Moreover, we also derived a complex model of D609, the only known small‐molecule inhibitor of hSMS1 so far. Our hSMS1 model may serve as a reasonable structural basis for the discovery of more effective small‐molecule inhibitors of hSMS1.