OXIDATION CHEMISTRY OF INDOLES

吲哚的氧化化学

• 批准号: 3281128
• 负责人: GLENN DRYHURST
• 金额: $ 10.62万
• 依托单位: UNIVERSITY OF OKLAHOMA
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-15 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3281128
• 关键词: 5 hydroxytryptophan; electrochemistry; indoles; neurotoxins; neurotransmitters; oxidation; quinones; serotonin; tryptophan

The aim of this project is to employ electrochemical and other analytical techniques to investigate the oxidation chemistry of naturally occurring or otherwise biologically significant indoles. These will include the 5-hydrosylated metabolites of tryptophan, N-methylated indoles (such as bufotenin) which are implicated in the etiology of schizophrenia and depression, and 5,6- and 5,7-dihydrosytryptamines (5,6- and 5,7-DHT) which are powerful neurotoxins. Anomalous, minor oxidation pathways of, for example, the enurotransmitter 5-hydrosytryptamine have been speculated to play a role in some mental disorders. Similarly, the neurotoxicity of 5,6- and 5,7DHT is thought to be due to reactions of their reactive autoxidation products in the CNA. Many of these indoles undergo oxidation reactions in biological systems yet virtually nothing is known about the mechanisms and products of these processes. Modern electroanalytical techniques will be used to elucidate the nature of the primary oxidation step and the identity and properties of transient intermediates. Longer lived intermediates will be further studied using spectral and chromatographic methods, particularly GC-MS and LC-MS techniques. Reaction products will be isolated and identified using a wide range of analytical techniques including column chromatography, HPLC, U.V.-vis, I.R., NMR and mass spectrometry. Evidence concerning the biological relevance of such studies will be obtained by investigating the oxidation of these indoles with various CNS enzymes and critically comparing the courses of the electrochemical and enzymatic oxidations. In vivo evaluations of the neurotoxic properties of the many new products formed by electrochemical and enzymatic oxidation are planned. Electrochemical and other analytical techniques will be used to study the interactions of the very reactive primary oxidation products of indoles (quinones, quinoneimines, methyleneimines) with nucleophiles commonly found in CNS tissue (thiols, amino acids, water). The long range goal is to develop a fundamental understanding of the oxidation chemistry of biologically significant indoles. This, in turn, could provide a basis for understanding the oxidation chemistry of such indoles in living systems which might give important insights into a chemical basis for some mental illnesses and other disease states.

这个项目的目的是利用电化学和其他分析方法 研究天然矿石氧化化学的技术 否则具有生物学意义的吲哚。这些将包括 色氨酸的5-氢化代谢物，N-甲基化吲哚(如 与精神分裂症和精神分裂症的病因学有关 以及5，6-和5，7-二氢系统色胺(5，6-和5，7-二羟色胺) 是一种强大的神经毒素。异常的，轻微的氧化途径 例如，神经递质5-羟色胺被推测为 在某些精神障碍中起作用。同样，5，6-的神经毒性- 和5，7DHT被认为是由于它们的反应性自氧化反应 CNA中的产品。这些吲哚中的许多都在 然而，对生物系统的机制和机制几乎一无所知 这些工艺的产品。现代电分析技术将是 用于阐明初级氧化步骤的性质和同一性 和瞬变中间体的性质。寿命更长的中间商将 利用光谱和层析方法进一步研究，特别是 GC-MS和LC-MS技术。反应产物将被分离并 使用包括柱子在内的各种分析技术进行识别 层析、高效液相色谱、紫外可见光谱、红外光谱、核磁共振和质谱学。证据 关于此类研究的生物学相关性，将通过以下方式获得 研究了不同中枢神经系统酶对吲哚的氧化作用 批判性地比较电化学课和酶课的课程 氧化作用。对多种药物的神经毒性特性的体内评估 通过电化学和酶催化氧化形成的新产品是 有计划的。将使用电化学和其他分析技术来 研究非常活泼的初级氧化产物之间的相互作用 含亲核试剂的吲哚类化合物(苯醌、喹酮亚胺、亚甲基亚胺) 常见于中枢神经系统组织(硫醇、氨基酸、水)。长距离的 目标是对氧化化学有一个基本的了解。 具有生物学意义的吲哚。这反过来又可以提供一个基础 了解这种吲哚在生命系统中的氧化化学 这可能会给我们提供一些重要的洞察力，让我们了解一些心理上 疾病和其他疾病状态。