BIMETALLIC COMPLEXES FOR POTENTIAL PHOTOCHEMOTHERAPY

用于潜在光化学治疗的双金属配合物

• 批准号: 6498888
• 负责人: Claudia Turro
• 金额: $ 17.86万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6498888
• 关键词: DNA binding protein; antineoplastics; chemical models; chemosensitizing agent; drug screening /evaluation; metal complex; molecular dynamics; neoplasm /cancer chemotherapy; neoplasm /cancer photoradiation therapy; nucleic acids; photoactivation; photobiology; platinum; rhodium

DESCRIPTION: (Adapted from applicant's abstract) The proposed research focuses on the use of ligand-bridged neutral and cationic d7-d7 and d8-d8 bimetallic metal complexes for photochemotherapy. Initiation of anti-tumor drug activity utilizing light has been an area of intense research with mixed success. The systems previously chosen for these studies have typically been fluorescent singlet excited states of organic molecules, their respective triplet states, or luminescent inorganic complexes. Problems encountered include short excited state lifetimes, high energy ultraviolet photons necessary for excitation, and the reaction of the photogenerated intermediates at undesired sites. A new avenue of research can be opened with the investigation of the non- or weakly-emissive excited states of mononuclear and bimetallic complexes, whose photophysical properties and reactivity remain largely unexplored. The potential advantages of these systems presented here include their increased redox reactivity through the presence of the metal center, their ability to be excited with visible light (lambda > 600 nm), and the ease with which they can be chemically modified to permit binding at selective DNA sites and to improve the excited state properties. Bimetallic systems that can be photoexcited with visible light to afford a reactive diradical excited state that can act as inorganic enediyne analogs, and whose reaction can be photoactivated. All of the molecules currently utilized in photodynamic therapy require oxygen for their activity since the excited states themselves are not reactive, therefore when the oxygen supply is depleted their reactivity is shut down. Our preliminary results show that the d7-d7 (RhII)2 systems can photocleave DNA effectively through the formation of singlet oxygen, however, the excited states themselves can photocleave duplex DNA. In addition to various dirhodium(II) complexes, we will also explore the excited state reactivity and DNA photocleavage by cationic d7-d7 (PtIII)2 and neutral d8-d8 (PtII)2 Systems

描述：（改编自申请人摘要）拟议的研究重点 关于使用配体桥连的中性和阳离子D7-D7和D8-D8 用于光化学疗法的金属络合物。抗肿瘤药物活性的起始 利用光是一个密集研究的领域，其成功与否参差不齐。的 以前为这些研究选择的系统通常是荧光的 有机分子的单重激发态，它们各自的三重态， 或发光无机复合物。遇到的问题包括短激励 状态寿命，激发所需的高能紫外光子，以及 光生中间体在不需要的位点的反应。一个新 通过对非或非现象的调查，可以开辟研究的途径 单核和单核络合物的弱发射激发态， 生物物理性质和反应性仍然在很大程度上未被探索。 本文介绍的这些系统的潜在优势包括： 通过金属中心的存在增加氧化还原反应性， 能够被可见光（λ> 600 nm）激发，并且易于 它们可以被化学修饰以允许在选择性DNA位点结合 并改善激发态性质。双金属系统， 用可见光光激发以提供反应性双自由基激发态 其可以作为无机烯二炔类似物，并且其反应可以 光活化的目前用于光动力疗法的所有分子 因为激发态本身不需要氧， 反应性，因此当氧气供应耗尽时，它们的反应性被关闭 下来我们的初步结果表明，d7-d7（RhII）2系统可以 通过单线态氧的形成有效地光切割DNA，然而， 激发态本身可以光切割双链体DNA。除了 各种dirhodium（II）配合物，我们也将探索激发态 阳离子d7-d7（PtIII）2和中性d8-d8的反应性和DNA光切割 （PtII）2系统