EXPLORING AND DEFINING THE ROLE OF LIGAND OXIDATION IN RU(II) ARENE-BASED DRUGS

探索和定义配体氧化在 RU(II) 芳烃类药物中的作用

• 批准号: 7954448
• 负责人: PIERRE KENNEPOHL
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954448
• 关键词: Antineoplastic Agents; Biochemical; Biological; Characteristics; Complex; Computer Retrieval of Information on Scientific Projects Database; Drug Delivery Systems; Environment; Funding; Grant; Institution; Ligands; Nature; Pharmaceutical Preparations; Pharmacologic Substance; Property; Research; Research Personnel; Resources; Role; Ruthenium; Selenium; Series; Source; United States National Institutes of Health; analog; base; drug candidate; metal complex; oxidation; structural biology; synchrotron radiation

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. Defining and understanding the mechanisms of action of pharmaceutical agents is an ongoing research challenge that requires detailed information on the reactivity of these drugs within a biological environment. The challenge is generally more complex for metal-based drug candidates due to their broader reactivity and the correspondingly greater possibilities for interactions during transport to the biological target. We are investigating the fundamental biochemical properties of a series of ruthenium-based drug targets with demonstrated antitumor activity. Ru arene complexes of the form [Ru(ar)(en)L]X have shown excellent activity as anticancer agents but the nature of L has an important, yet somewhat unpredictable effect on bioactivity. We note particularly that thiolato complexes (L=RS-) are extremely bioactive under acidic and oxidative conditions. The properties of different oxidized forms of these complexes (e.g. L=RSO-, RSOH, RSO2-, RSO2H) and their related selenium analogs are currently being explored and show unusual bonding characteristics that are believed to be very relevant to their bioactivity. We therefore propose to utilize S K-edge and Se K-edge XAS (as well as other ligand K-edges where appropriate) to evaluate the nature of Ru-X bonding in these and related species.

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