DEVELOPMENT OF ADDUCTPPERSISTENT SPIN TRAPS/SUPEROXIDE

超氧阴离子自由基参与多种病理过程 流程。它在生物系统中的作用和存在的研究 自旋俘获方法由于原子的不稳定性而受到阻碍。 超氧化物加合物。一些新近开发的磷酸化硝酮，而 就体内加合物的稳定性而言，仍远未达到理想水平 展示了独特而耐人寻味的改进。这一阶段的目标是进行 进行了一系列实验，以测试所提出的稳定机制 一种已知的超氧化物加合物。合成了两个密切相关的新的 硝化甘油也将被追查。取决于成功的合成和 在资源允许的范围内，他们的超氧化物加合物 以类似方式进行审查，以进一步验证和/或完善拟议的 机制。半经验计算表明，所提出的机制 会使超氧化物加合物稳定5到33千卡/摩尔，而那个 新的超氧化物加合物的稳定性比 现有的模拟设备。对稳定效应产生原因的认识 将允许对超氧化物的最佳自旋陷阱进行合理设计 生物系统。可以设计这种优化的自旋陷阱， 合成，并在第二阶段测试。

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.