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.

包含卟啉家族的分子是最通用的 自然界的假肢群体。 呼吸中的电子穿梭，结合 并运输氧气，并在多种氧化还原的活跃部位服务 酶和电子传输链只是突出的少数 卟啉分子的活性。 卟啉与 其他分子的各种阵列和卟啉的合成模型系统 介导过程使得分子相互作用探测，并 以精确的精度确定。 我们的长期目标是准备 合成卟啉模型系统，并深入了解卟啉 介导的生物过程。 为了实现这一目标，需要能力 构建具有三维阶列卟啉的系统 和附件分子。 我们的具体目标是； 1）。 调查，完善和扩大高浓度的范围 有氧卟啉合成，以实现折衷的合成 使用Adler方法的简单性和制备规模的方法 室温合成的牛奶条件和范围。 2）开发一组用于制备卟啉轴承的合成方法 四个不同的中氧化剂（ABCD-porphyrins）。 这种方法将 提供局部卟啉环境的详细建筑控制 并启用研究由卟啉介导的现象与 其他分子的集合，例如电子传输链。 3）开发简单且合理的路线，具有用于中索的功能 在氢磷酸酯（例如氯蛋白）的光谱中取代 细菌氯蛋白，等杆菌，腐病蛋白，最终是corphins。 该方法将导致自然发生的模型研究 氢磷脂，例如绿色下摆，sirohemss，F430和最终维生素 B12，并实现了氢磷脂互变异素化的基本研究。 这些路线将使减少卟啉的通用模型几乎一样 现在可以作为卟啉模型系统访问。 4）研究我们新的轻度合成镁的一般性 卟啉，将其扩展到天然和合成的氢磷脂，以及 确定光谱镁螯合物的热力学稳定性 卟啉和水源性。 总之，这些研究将导致一般进步 卟啉化合物模型系统的艺术状态，并加深我们 了解基本化学和功能多功能性 四吡咯粒大环的基本和迷人的家族。