PORPHYRIN SYNTHETIC METHODS FOR BIOORGANIC APPLICATIONS

用于生物有机应用的卟啉合成方法

• 批准号: 2178231
• 负责人: JONATHAN SIDNEY LINDSEY
• 金额: $ 26.33万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 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 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2178231
• 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最通用的 自然界中的辅基 在呼吸中穿梭电子， 和运输氧，并在各种氧化还原的活性位点服务 酶和电子传递链只是其中几个突出的 卟啉分子的活性。 卟啉与一种 各种各样的其他分子，以及卟啉的合成模型系统- 介导的过程使得能够探测分子相互作用， 以精确的精确度来识别。 我们的长期目标是 合成卟啉模型系统，并深入了解卟啉- 介导的生物过程。 要实现这一目标，需要有能力 为了构建具有3维有序性的系统， 和辅助分子。 我们的具体目标是： 1）。 调查、细化、拓宽高度集中的范围 有氧卟啉合成，以实现折衷的合成 方法的简单性和Adler方法的重复性， 牛奶的条件和范围的室温合成。 2)开发了一套制备含卟啉化合物的合成方法 四种不同的中位取代基（ABCD-卟啉）。 这种方法将 提供当地卟啉环境的详细建筑控制 并且能够研究由卟啉介导的现象， 其他分子的集合，如电子传递链。 3)开发简单合理的路线，具有中- 氢卟啉，如二氢卟酚， 细菌绿素、异细菌绿素、coroles和最终的corphins。 该方法将导致自然发生的模型研究 氢化卟啉如绿色血红素、sirohemss、F430和最终维生素 B12，使氢卟啉互变异构的基础研究。 这些路线将使还原卟啉的通用模型几乎 现在卟啉模型系统是可获得的。 4)研究我们新的温和合成镁的一般性 卟啉，将其扩展到天然和合成的氢化卟啉， 测定光谱的镁螯合物的热力学稳定性 卟啉和氢卟啉的合成。 综合这些研究， 卟啉类化合物模型体系的研究现状， 了解基础化学和功能的多功能性， 四吡咯大环化合物的重要而迷人的家族。