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: 8362129
• 负责人: KAREN L MCFARLANE
• 金额: $ 0.25万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362129
• 关键词: Ants; Biological; Biological Process; Cancerous; Cells; Chemical Structure; Chloride Ion; Chlorides; Complex; DNA-Binding Proteins; Data; Dimethyl Sulfoxide; Drug Design; Electron Transport Complex III; Funding; Future; Grant; Imidazole; In Vitro; Indazoles; Investigation; Libraries; Ligands; Measurement; Metals; National Center for Research Resources; Principal Investigator; Radiation; Research; Research Infrastructure; Resources; Sampling; Solid; Solutions; Source; United States National Institutes of Health; base; cost; electronic structure; in vitro Model; in vitro activity; in vivo; insight; member; process optimization; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们提出了一个系统的多边XANES研究来确定与体外活性相关的基于Ru的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，从而辅助药物设计和优化过程。在配体(S和氯)K-和金属(Ru)L边收集的光谱信息将提供对Ru(II)和Ru(III)配合物的电子结构的深入了解。此外，还将对结构不明确的溶液样品进行金属(Ru)K边光谱的EXAFS分析。我们合成了大量的Ru(III)和Ru(II)与二甲基亚砜、氯化物、咪唑和吲唑的配合物。我们已经获得了一些配合物的ClK边和Ru L边数据，并确定了可能作为生物活性特征的光谱特征。我们计划将这些研究扩展到我们的Ru复合体文库的10个成员，在中性和酸性(癌细胞)pH条件下，纯固体、水解态、DNA和蛋白质结合形式。这些体外模拟研究有可能为未来的体内研究提供基础。此外，体外测量将补充电子结构计算，以帮助指定光谱，并为获得溶液样品的结构信息提供合理的依据。