【作者】 张巍；

【导师】 赵冰；

【作者基本信息】 吉林大学 ， 物理化学， 2010， 博士

【摘要】 本论文将表面增强拉曼散射(SERS)光谱技术与传统的光谱学方法相结合,建立了两种基于SERS的药物分子-人血清白蛋白分子复合物的分析检测方法,即在固体增强基底上和生理缓冲液环境中研究药物分子的空间取向变化信息。本文所应用的药物分子包括原小檗碱类、黄酮类和黄酮醇类共三类十一种临床应用较为广泛的药物分子。主要创新性研究成果如下:(1)首次利用原小檗碱类药物分子和人血清白蛋白分子在金属纳米粒子表面自组装SERS活性基底。在固相基质上先组装好金属纳米粒子,然后再依靠原小檗碱类药物分子和人血清白蛋白分子与金属纳米粒子间的相互作用形成SERS基底。该方法的最大特点是简单、快速、重复性好。(2)通过SERS与荧光、紫外光谱的结合,建立了一种在生理缓冲液条件下黄酮类药物分子与人血清白蛋白分子结合后空间取向变化的分析方法。普通拉曼和理论计算拉曼的应用为黄酮类药物分子中各官能团的基本振动模式提供了指认。此外,利用银溶胶体系作为SERS活性基底,首次在缓冲溶液中比较研究了四种黄酮类同系物分子由于结构差异所导致的空间取向变化。(3)通过SERS与荧光、紫外光谱的结合,建立了一种在生理缓冲条件下黄酮醇类药物分子与人血清白蛋白分子结合后空间取向变化的分析方法。黄酮醇类药物分子与黄酮类药物分子相比在许多性质方面都有特异性,利用SERS检测灵敏度高的特性,在缓冲溶液状态下获得了四种黄酮醇类药物分子与人血清白蛋白分子之间的结合方式。更多还原

【Abstract】 As an ultrasensitive analytical technique, surface-enhanced Raman scattering (SERS) has been attracted increasing attention in pharmaceutical molecules science. SERS-based methods have salient advantages of high sensitivity, photostability and spectral multiplexing over conventional methods, based on which we successfully developed two SERS-based detection methods for pharmaceutical molecule-Human Serum Albumin (HSA) complex. The major contributions of this work are as follows:(1) Solid-enhanced substrate fabricating and HSA-mediated orientation of protoberberine alkaloidsWe developed a new simple method by depositing silver colloid on modified glass, which is an excellent SERS-active substrate for protoberberine-HSA complex. The proposed method is facile and sensitive, and the most important thing is after recognition, we can determine different pharmaceutical molecules by SERS, which is accessible for identifying the orientation of pharmaceuticals.(2) The orientation of flavonoids influenced by HSA in aqueous solutionsFluorescence and ultraviolet-visible spectra are basic and efficient methods to identify the recognition between flavonoids and HSA, while the information about the flavonoid’s structure is limited. The SERS spectra are obtained in silver colloid in physiological conditions, then the various orientation based on different structure will be embodied.(3) Based on physiological SERS substrate to detect the flavonol-HSA complexThe flavonols are quite different from flavonoids not only in physical and chemical properties, but also in physiological activities. The silver nanoparticles are used as the SERS substrate in pH 7.4 aqueous solutions, and then vibrational information of flavonols will be probably displayed in their SERS spectra with remarkable enhanced reproducibility. When in the flavonol-HSA complex, the SERS intensity of different vibrations will stand for the changing orientation of flavonols.更多还原