SYNTHESIS, ANALYSIS, TOXICITY SCREENING AND COMPUTATIONAL CHEMISTRY OF ARYLPHOSP

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 化学和生物学本科生将利用在有机化学和微生物学中学到的实验台、仪器和计算化学方法，完成与脂质或多肽结合的芳基膦阳离子的合成和表征、毒性筛选、层析和计算分析，并在应用于研究项目时加以应用和提炼。复合型通常具有细胞毒性。它聚集在恶性肿瘤细胞的线粒体中，与乙酰胆碱清除酶结合，移动天然DNA的熔化曲线，杀死培养中的各种革兰氏阳性细菌和恶性肿瘤细胞。将分别进行QSAR、分子力学和分子动力学计算，以找到与活性(QSAR)的相关性和预测值，确定DNA/粘合剂对接的几何形状和能量(Mm)，并观察在存在和不存在粘结剂的情况下dsDNA的热降解(Md)。使用离子对技术的反相高效液相色谱和薄层色谱将被用来确定与生物利用度相关的物理参数。在50-100毫克范围内的化合物的微尺度合成、提纯和分析将帮助学生提高实验技术的精确度和精密度。他们将例行地准备样品，并获取和分析IR、核磁共振、UV和(在某些情况下)荧光光谱。LC-MS将取代元素分析用于新化合物的结构验证。一个或多个将进行Kirby-Bauer抗菌筛查。这些学生将在教师导师的指导下挣钱支持他们的教育，同时获得实验室研究的经验。这将为打算从事化学、生物、医学或药理学研究生工作的个人提供支持和培训，并帮助他们为在工业中担任化学、生物或健康相关职位的入门级(学士和学士)职位做准备。这些学生在我们系中从事这项工作的高调存在，将有助于吸引其他人考虑从事研究工作。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Synthesis and characterization, toxicity screening, chromatography, and computational analysis of arylphosphonium cations conjugated with lipids or polypeptides will be done by undergraduate chemistry and biology students in which they will use experimental bench, instrumental, and computational chemistry methods learned in organic chemistry and microbiology and apply and refine them in application to a research project. The compound type is generally cytotoxic. It accumulates in mitochondria of malignant cells, binds to acetylcholineserase, shifts the melting curve of native DNA, kills a variety of gram-postive bacteria, and malignant cells in culture. QSAR, molecular mechanics, and molecular dynamics calculations will be done, repectively; to find correlations with and predictors of activity (QSAR), to determine DNA/Binder docking geometries and energies (mm), and to observe thermal degradation of dsDNA with and without a binder present (md). Reversed-phase HPLC and TLC using ion-pair techniques will be used to determine chromatographic constants that are physical correlates of bioavailability. Microscale synthesis, purification and analysis of compounds at the 50-100 mg scale will help students develop accuracy and precision in experimental technique. They will routinely prepare samples and acquire and analyze IR, NMR, UV and (in some cases) fluoresence spectra. LC-MS will be used in lieu of elemental analysis as verification of structure for new compounds. One or more will do Kirby-Bauer antibacterial screening. The students will earn money to support their education while gaining experience in laboratory research under the direction of faculty mentors. This will provide support and training for individuals who intend to pursue graduate work in chemistry, biology, medicine, or pharmacology, as well as help prepare them for entry-level (BA and BS) positions in chemistry, biology or health-related positions in industry. The high-profile presence of these students doing this work in our departments will help attract others to consider careers in research.