DEVELOPMENT OF ADDUCTPPERSISTENT SPIN TRAPS/SUPEROXIDE

加合物持续自旋陷阱/超氧化物的开发

• 批准号: 2662877
• 负责人: DIEM D LE
• 金额: $ 8.98万
• 依托单位: LE RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2662877
• 关键词: adduct; chemical stability; chemical structure function; chemical synthesis; method development; nitrone; superoxides

Superoxide anion radical participates in a variety of pathological processes. Studies of its role and occurrence in biological systems via the spin trapping method have been impeded by the instability of the superoxide-adducts. Some recently developed phosphonated nitrones, while still far short from ideal in terms of adduct stability in vivo, have exhibited unique and intriguing improvements. This Phase I aims to carry out a series of experiments to test a proposed mechanism of stabilization for a known superoxide-adduct. Synthesis of two new, closely related nitrones will also be pursued. Contingent on a successful synthesis and to the extent the resources permit, their superoxide-adducts will be similarly examined to further validate and/or refine the proposed mechanism. Semi-empirical calculations suggest that the proposed mechanism would stabilize the superoxide-adducts by 5 to 33 Kcal/mol, and that one of the new superoxide-adducts is considerably more stable than the existing analog. An understanding of the causes of the stabilizing effects will allow a rational design of optimal spin traps for superoxide in biological systems. Such optimized spin traps may be designed, synthesized, and tested in Phase II.

超氧阴离子自由基参与多种病理过程 流程.研究其在生物系统中的作用和发生， 自旋捕获方法已经受到 超氧化物加合物一些最近开发的膦酸化硝酮，而 就加合物体内稳定性而言，仍远未达到理想， 展现出了独特而有趣的进步第一阶段的目标是 进行了一系列的实验来测试一种被提出的稳定机制 对于已知的超氧化物加合物。合成两个新的，密切相关的 硝酮也将被追求。取决于成功的合成， 在资源允许的范围内，它们的超氧化物加合物将是 进行类似的检查，以进一步验证和/或完善拟议的 机制半经验计算表明，提出的机制， 将使超氧化物加合物稳定5至33千卡/摩尔， 新的超氧化物加合物的稳定性要比 现有的模拟。对稳定效应的原因的理解 将允许合理设计超氧化物的最佳自旋陷阱， 生物系统。可以设计这种优化的自旋陷阱， 合成，并在第二阶段进行测试。