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: 8170058
• 负责人: KAREN L MCFARLANE
• 金额: $ 0.58万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170058
• 关键词: Ants; Biological; Biological Process; Cancerous; Cells; Chemical Structure; Chloride Ion; Chlorides; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA-Binding Proteins; Data; Dimethyl Sulfoxide; Drug Design; Electron Transport Complex III; Funding; Future; Grant; Hydrolysis; Imidazole; In Vitro; Indazoles; Institution; Investigation; Libraries; Ligands; Measurement; Metals; Research; Research Personnel; Resources; Sampling; Solid; Solutions; Source; United States National Institutes of Health; base; electronic structure; in vitro Model; in vitro activity; in vivo; insight; member; process optimization

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们提出了一项系统的多边缘XANES研究，以确定基于RU的抗癌金属果的光谱特征，该抗体与体外活性相关。这将使从化学结构中预测生物功能，从而有助于药物设计和优化过程。在配体（s和cl）K-和金属（RU）L-边缘收集的光谱信息将提供对RU（II）和RU（III）复合物的电子结构的见解。这些将补充对结构不确定的溶液样品的金属（RU）K边缘光谱的EXAFS分析。我们已经合成了一个大的RU（III）和RU（II）复合物与二甲基硫氧化物，氯化物，咪唑和吲哚唑配体的库。我们已经为某些复合物获得了Cl K-Edge和Ru l-Edge数据，并确定了可能是生物活性签名的候选光谱特征。我们计划在中性和酸性（癌细胞）pH条件下以纯固体，水解，DNA和蛋白质结合的形式扩展到RU复合文库的十名成员。这些体外建模研究有可能提供体内研究未来的基础。同样，体外测量将补充电子结构计算，以帮助光谱分配，并为溶液样品获得的结构信息提供了合理的理性。