MASS SPECTROMETRY STUDIES ON RADICAL REACTIONS OF DNA

描述：(改编自申请者的摘要)许多DNA的作用 切割药物的基础是形成一种反应性的多原子单核-或 然后从DNA中的糖部分中提取氢原子的双自由基， 导致链断裂。了解控制经济增长的因素 他的氢原子提取反应的效率对 战略性抗肿瘤和抗病毒药物设计。然而，目前几乎没有 了解这些因素或了解反应性自由基的性质 由毒品形成的中间体。本研究通过使用以下方法解决这些问题 质谱学实验检测有机化合物的本征反应性 不同取代的苯基和双自由基与 抗肿瘤和抗病毒(艾滋病)药物的作用。其结构特点是 探索了确定自由基能从 脱氧核糖及其对不同氢原子的选择性 对不同物质的反应性。溶剂效应可通过以下方式解决 考察作为逐步溶剂化作用的反应。实验性的 数据由从分子中获得的热化学信息来补充 轨道计算。除了检查以下因素外， 控制已知类型的非水解性DNA切割器的反应性，各种 对新颖的单、双和三个自由基进行了抽提能力的筛选 来自DNA的氢原子。其目标是发现高效的dna切割器。 这可能为开发新型汽车提供基础。 制药公司。此外，利用光解产生DNA裂解 探索自由基是为了推进人工DNA的设计 用于特定部位医疗的照片裂解剂。最后， 对捕获自由基的不同方法进行了评估，以期在 预防阿尔茨海默病等疾病引起的自由基损伤S 疾病和中风。

DESCRIPTION: (Adapted from the applicant's abstract) The action of many DNA cleaving drugs is based on the formation of a reactive polyatomic mono- or biradical that then abstracts a hydrogen atom from a sugar moiety in DNA, inducing a strand cleavage. Understanding the factors that control the efficiency of his hydrogen atom abstraction reaction is crucial for strategic antitumor and antiviral drug design. However, little is currently known about these factors or about the properties of the reactive radical intermediates formed from drugs. This study addresses these issues by using mass spectrometry experiments to examine the intrinsic reactivity of differently substituted phenyl radicals and biradicals pertinent to the action of antitumor and antiviral (AIDS) drugs. The structural features are explored that determine a radicals ability to abstract a hydrogen atom from deoxyribose, its selectivity toward different hydrogen atoms, and its reactivity toward different substances. Solvent effects are addressed by examining reactions as a function of stepwise solvation. The experimental data is complemented by thermochemical information obtained from molecular orbital calculations. In addition to examination of the factors that control the reactivity of known types of nonhydrolytic DNA cleavers, various novel mono-, bi- and triradicals are screened for their ability to abstract a hydrogen atom from DNA. The goal is to discover efficient DNA cleavers that may provide the basis for the development of new types of pharmaceuticals. Further, the use of photolysis to generate DNA-cleaving radicals is explored as an effort to advance the design of artificial DNA photo cleaving agents for site-specific medical treatments. Finally, different methods to trap radicals are evaluated for possible application in prevention of free radical damage caused by such conditions as Alzheimer s disease and strokes.