【作者】 杨琼；

【导师】 张其颖；

【作者基本信息】 华东师范大学 ， 无机化学， 2011， 硕士

【摘要】 钒作为人体必需的微量元素,在葡萄糖的代谢过程中起着非常重要的作用。钒的化合物具有模拟胰岛素的生理功能,是一类有良好应用前景的糖尿病治疗药物。目前研究发现：无机钒化合物具有较好的类胰岛素活性,目前已有少数投入到临床试验阶段。但是无机钒酸盐的毒性大、脂溶性小、生物利用度低、所需剂量大,于是人们的研究兴趣又转向了钒的有机配合物。因此,选择适当的配体或者配位原子与其结合,克服无机钒化合物的缺陷,以达到促进吸收、提高药效和降低毒性的目的。因此,钒的有机配合物引起了包括生物、化学和医药等众多研究领域的关注。本论文设计合成了两类钒配合物,一类是以吡啶羧酸羟胺钒,另一类是以多钒磷酸簇合物,并对其进行了表征；同时研究了配合物的蛋白质酪氨酸酶PTP1B筛选和抑菌肺炎克雷柏菌活性实验。具体工作如下：第一：设计合成了两种新的吡啶羧酸羟胺钒配合物,以2-吡啶一甲酸和2,3吡啶二甲酸为配体,在水溶液和中性pH值的条件合成了2-吡啶一甲酸羟胺钒配合物、2,3吡啶二甲酸羟胺钒钾配合物。对新合成的配合物进行了一系列的表征和测试,确定了配合物的基本组成和配位情况,主要测试包括：元素分析、红外光谱分析、紫外光谱分析、热重分析和X-射线单晶衍射。第二：设计合成了一种新的多钒磷酸盐,以磷原子为配位原子,在水溶液、高温和高压反应釜中合成。利用元素分析、红外光谱分析、紫外光谱分析、热重分析和X-射线单晶衍射研究了配合物的组成、分子结构和晶体结构。第三：对新合成的配合物进行了一系列性能测试。主要包括：配合物的脂溶性研究(分配系数的测定)：选择了正辛醇/KRB(pH=7.4)生理缓冲溶液体系,分别测定钒配合物两相中的吸光度,计算得其分配系数；活性测试：进行了蛋白酪氨酸磷酸酶PTP1B模型实验和抑菌肺炎克雷柏菌活性实验,活性实验得到的初步结论为进一步研究和建立本系列配合物作为胰岛素模拟物的构效关系奠定了基础。更多还原

【Abstract】 Vanadium has been proposed and accepted to be an essential trace element in the glucose metabolism. Vanadium compounds possess the physiological effects in simulating physiological functions of insulin, and have a good prospect acting as a class of diabetes drugs. Now Inorganic vanadium compounds and Organic vanadium coordination compounds are synthesised. It has been found that some Inorganic vanadium compounds have the better insulin effects and have been used in clinical tests.But inorganic vanadates has many drawbacks, such as:toxicity, small fat-solubility, low bioavailability and dose requirements, so great attention has been paid to organic vanadium complexes. Therefore,we should select the appropriate ligands or coordinated atoms to overcome the drawbacks of the Inorganic vanadium compounds. Now, Organic vanadium compounds have been the popular topics in the current bio-inorganic chemistry.In this paper, two categories of vanadium(V) complexes were synthesized and characterized. One is the vanadium pyridine carboxylic acid hydroxylamido and the other is polyoxovandates phosphate complex. We had studied the PTP1B protein tyrosinase activity and Bacteriostatic pneumonia clay cypress bacteria experiments. The main work of the research as follows:1. Two new vanadium(V) pyridine hydroxylamido complexes with 2-pyridine carbonic acid and 2,3-pyridine two carbonic acid were prepared in neutral solution. The basic compositions of the complexes were determined by the elemental analysis, thermogravimetric analysis, the IR, the UV spectra and the single crystal diffraction analysis respectively.2. One new Vanadium phosphate complex with P atom was synthesized in the water solution high temperature and Teflon-lined stainless steel autoclave. By the elemental analysis, thermogravimetric analysis, the IR, the UV spectra and the single crystal diffraction analysis, the composition、molecular structure and crystal structure were studied. 3. A series performance of new synthesized complexes were tested, including Fat-solubility study(determination of the partition coefficient):The absorbance of vanadium complexes dissolved in a Krebs-Ringer bicarbonate (K.RB) buffer (pH=7.4) /n-octanol system were determinated respectively, and its partition coefficient was calculated in accordance with formula; Activity test:The protein tyrosine phosphatase PTP1B and Bacteriostatic pneumonia clay cypress bacteria experiments were carried out. The preliminary conclusion is a basis for further research and establishment of structure-activity relationship of vanadium complexes as insulin mimics.更多还原