PORPHYRIN SYNTHETIC METHODS FOR BIOORGANIC APPLICATIONS

用于生物有机应用的卟啉合成方法

• 批准号: 2734539
• 负责人: JONATHAN SIDNEY LINDSEY
• 金额: $ 23.21万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1999-12-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2734539
• 关键词: chemical condensation; chemical models; chemical substitution; chemical synthesis; chlorin; electron spin resonance spectroscopy; heme; magnesium; phthalocyanin; porphyrins; pyrroles; tautomer; thermodynamics

The molecules comprising the porphyrin family are the most versatile prosthetic groups in nature. Shuttling electrons in respiration, binding and transporting oxygen, and serving in the active sites of diverse redox enzymes and electron transport chains are only a few of the prominent activities of porphyrinic molecules. Porphyrins work in concert with a diverse array of other molecules, and synthetic model systems of porphyrin- mediated processes enable the molecular interactions to be probed and identified with exacting precision. Our long-term goals are to prepare synthetic porphyrin model systems and to gain deep insight into porphyrin- mediated biological processes. To achieve this goal requires the ability to construct systems having 3-dimensional order incorporating porphyrinic and accessory molecules. Our specific aims are to; 1). Investigate, refine, and broaden the scope of the high concentration aerobic porphyrin synthesis, in order to achieve an eclectic synthetic method with the simplicity and preparative-scale of the Adler method and the milk conditions and scope of the room temperature synthesis. 2) Develop a set of synthetic methods for preparing porphyrins bearing four different meso-substituents (ABCD-porphyrins). This methodology will provide detailed architectural control of the local porphyrin environment and enable study of phenomena mediated by porphyrins in conjunction with collections of other molecules, such as in electron transport chains. 3) Develop simple and rational routes with capabilities for meso- substitution in the spectrum of hydroporphyrins, such as chlorins, bacteriochlorins, isobacteriochlorins, corroles, and ultimately corphins. The methodology will lead to model studies of naturally occurring hydroporphyrins such as green hemes, sirohemss, F430 and ultimately vitamin B12, and enable fundamental studies of hydroporphyrin tautomerization. These routes will make versatile models of reduced porphyrins nearly as accessible as porphyrin model systems are now. 4) Investigate the generality of our new mild synthesis of magnesium porphyrins, extend it to natural and synthetic hydroporphyrins, and determine the thermodynamic stability of magnesium chelates of a spectrum of porphyrins and hydroporphyrins. Taken together these studies will lead to a general advancement in the state of the art of model systems of porphyrinic compounds and deepen our understanding of the fundamental chemistry and functional versatility of the essential and fascinating family of tetrapyrrolic macrocycles.

组成卟啉家族的分子是用途最广的 自然界中的假肢群体。在呼吸作用中穿梭电子，结合 以及运输氧气，并在各种氧化还原的活性部位提供服务 酶和电子传输链只是突出的几个 卟啉类分子的活性。卟啉与一种 不同的其他分子阵列，以及合成的卟啉模型系统- 中介过程使分子间的相互作用能够被探测和 以严格的精确度识别。我们的长期目标是准备 合成的卟啉模型系统，并深入了解卟啉- 中介的生物过程。要实现这一目标，需要有能力 构建含卟啉的三维有序体系 和附属物分子。 我们的具体目标是； 1)。调查、细化、拓宽高浓度的范围 好氧合成卟啉，以实现折衷合成 方法具有Adler法的简单性和制备规模 研究了牛乳的常温合成条件和范围。 2)开发了一套制备含卟啉化合物的合成方法。 四种不同的中间取代基(ABCD-卟啉)。这种方法论将 提供对当地卟啉环境的详细建筑控制 并使研究由卟啉与 其他分子的集合，例如在电子传输链中。 3)开发简单合理的中观路径 氢卟啉光谱中的取代物，如氯素， 细菌素、异细菌氯素、腐蚀物，最终是珊瑚毒素。 这种方法论将导致自然发生的模型研究 氢卟啉，如绿血球、西红血球、F430和最终的维生素 B12，并使氢卟啉互变反应的基础研究成为可能。 这些路线将使还原的卟啉的通用模型接近于 就像现在的卟啉模型系统一样容易获得。 4)研究我们新的温和合成镁的通用性 卟啉，将其扩展到天然和合成的氢卟啉，以及 测定光谱中镁络合物的热力学稳定性 一系列的卟啉和氢卟啉。 综上所述，这些研究将导致在 卟啉化合物模型体系的最新进展和深化我们的 对基础化学和功能多功能性的理解 四聚吡咯大环的基本而迷人的家族。