A Chemical Model for the Prebiotic Origins of Tetrapyrrole Macrocycles

该奖项将资助北卡罗来纳州立大学的乔纳森·S·林赛博士在看似合理的益生菌条件下探索四聚吡咯大环的形成和可能的光化学性质。形成需要一个多阶段的过程，从简单的非环反应物开始，通过反应性的吡咯进行到卟啉原，后者在氧化时产生卟啉。组合反应提供了一种复杂的四吡咯大环混合物，它们自发地在水泡和膜泡之间分配。一个关键的目标是了解这种自组织化学的范围和稳定性，特别是在反应可能并行进行的情况下。第二个主题是使用定量分析方法，将这种丰富的化学物质建立在坚实的物理基础上。所获得的知识将为支持原新陈代谢和原光合作用过程的一系列强有力的催化剂(四吡咯)的可能起源和功能提供一个化学模型。生命的起源是一个持久的和未被满足的科学挑战。四氢吡咯大环(例如，叶绿素)在所有生物体中发挥着核心作用，并被认为在生命起源中发挥着核心作用，但它们的益生起源仍然不清楚。虽然确切的起源可能永远不会被知道，但一个可行的化学模型的发展，受早期地球条件的限制，可以为四吡咯分子的可能起源提供洞察。这项拟议的研究让本科生和研究生从事具有内在跨学科特点的科学研究(合成原料、执行化学反应、分析复杂的化合物混合物、结合地球科学的考虑评估益生菌的影响)。林赛教授每年为大四本科生和研究生讲授一门配套课程(生命的分子起源)，在令人着迷的益生菌化学领域的背景下阐述基本化学原理。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Jonathan S. Lindsey from North Carolina State University to probe the formation and possible photochemical properties of tetrapyrrole macrocycles under plausible prebiotic conditions. The formation entails a multistage process beginning with simple acyclic reactants and proceeds through a reactive pyrrole on to porphyrinogens, which upon oxidation yield porphyrins. Combinatorial reactions afford a complex mix of tetrapyrrole macrocycles that spontaneously partition among aqueous and membrane vesicles. A key objective is to understand the scope and robustness of this self-organizing chemistry, particularly where reactions may proceed in parallel. A second theme is to employ quantitative analytical methods that place this rich chemistry on a firm physical basis. The knowledge gained will provide a chemical model for the possible origins and function of a potent set of catalysts (tetrapyrroles) supporting proto-metabolism and proto-photosynthetic processes.The origin of life is an enduring and unmet scientific challenge. Tetrapyrrole macrocycles (e.g., chlorophylls) play a central role in all living organisms and have been proposed to play a central role in the origin of life, yet their prebiotic origin has remained obscure. While the exact origins may never be known, the development of a viable chemical model, bounded by constraints of early earth conditions, could provide insight into the possible origins of tetrapyrrole molecules. The proposed research engages undergraduate and graduate students in scientific research with an inherently interdisciplinary flavor (synthesize starting materials, perform chemical reactions, analyze complex mixtures of chemical compounds, assess the prebiotic implications in coordination with earth sciences considerations). A companion course (Molecular Origins of Life), taught by Professor Lindsey annually for senior undergraduates as well as graduate students, addresses fundamental chemical principles in the context of the fascinating field of prebiotic chemistry.