METAL (RU) AND LIGAND K-EDGES (S, CL) AND METAL L-EDGE (RU) INVESTIGATION OF ANT

ANT 的金属 (RU) 和配体 K 边缘 (S、CL) 和金属 L 边缘 (RU) 研究

• 批准号: 7722043
• 负责人: KAREN L MCFARLANE
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722043
• 关键词: Ants; Biological; Biological Process; Cancerous; Cells; Chemical Structure; Chloride Ion; Chlorides; Classification; Complex; Computer Retrieval of Information on Scientific Projects Database; Condition; DNA-Binding Proteins; Data; Dimethyl Sulfoxide; Drug Design; Electron Transport Complex III; Electronics; Funding; Future; Grant; Hydrolysis; Imidazole; In Vitro; Indazoles; Institution; Investigation; Libraries; Ligands; Measurement; Metals; Process; Research; Research Personnel; Resources; Sampling; Solid; Solutions; Source; Structure; United States National Institutes of Health; base; in vitro Model; in vivo; insight; member

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. We propose a systematic multi-edge XANES study to determine spectroscopic signatures for Ru-based anticancer metallodrugs that correlate with in vitro activity. This would make possible the prediction of biological function from chemical structure and thus aid the drug design and optimization process. Spectral information collected at the ligand (S and Cl) K- and metal (Ru) L-edges will provide insights into the electronic structure of Ru(II) and Ru(III) complexes. These will be supplemented with EXAFS analysis of metal (Ru) K-edge spectra for structurally ill-defined solution samples. We have synthesized a large library of Ru(III) and Ru(II) complexes with dimethylsulfoxide, chloride, imidazole, and indazole ligands. We have already obtained Cl K-edge and Ru L-edge data for some of the complexes and identified spectral features that could be candidates for signatures of biological activity. We plan to extend these studies to ten members of our Ru complex library in pure solid, hydrolyzed, DNA, and protein bound forms at neutral and acidic (cancerous cells) pH conditions. These in vitro modeling studies have the potential to provide the base of future in vivo studies. Also, the in vitro measurements will be supplemented with electronic structure calculations to aid the spectral assignments and provide rational for the structural information obtained for solution samples.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们提出了一项系统性的多边 XANES 研究，以确定与体外活性相关的钌基抗癌金属药物的光谱特征。这将使从化学结构预测生物功能成为可能，从而有助于药物设计和优化过程。在配体（S 和 Cl）K 边缘和金属（Ru）L 边缘收集的光谱信息将有助于深入了解 Ru(II) 和 Ru(III) 配合物的电子结构。这些将通过 EXAFS 对结构不明确的溶液样品的金属 (Ru) K 边光谱分析进行补充。我们合成了一个大型的 Ru(III) 和 Ru(II) 配合物库，其中包括二甲亚砜、氯化物、咪唑和吲唑配体。我们已经获得了一些复合物的 Cl K 边缘和 Ru L 边缘数据，并确定了可能作为生物活性特征候选的光谱特征。我们计划将这些研究扩展到中性和酸性（癌细胞）pH 条件下纯固体、水解、DNA 和蛋白质结合形式的 Ru 络合物库的 10 个成员。这些体外建模研究有可能为未来的体内研究提供基础。此外，体外测量将辅以电子结构计算，以帮助光谱分配并为从溶液样品获得的结构信息提供合理的信息。