Mechanism of Alkene Oxidation by Photodeoxygenation

在化学结构、动力学和机制-B项目的支持下，圣路易斯大学的瑞安·麦卡拉教授研究了生物氧化的化学途径。当某些含环分子暴露在紫外线或可见光下时，就会形成高活性的原子氧。这种被称为光化学分解的反应可以被仔细地指导，以便原子氧在生物细胞膜中非常特定的位置形成。一旦原子氧形成并释放，它就可以攻击其他生物分子中的碳-碳双键。更多地了解光如何以及何时可以用来产生原子氧，以及这种氧如何攻击其他分子(在一个称为氧化应激的过程中)，可能会使科学家开发出由光而不是其他化学物质启动的新疾病疗法。氧化应激与心血管疾病、糖尿病和吸烟有关。这项研究有助于研究氧化应激对细胞膜的生理影响。从长远来看，这项工作可能会对社会的健康和福祉产生有益的影响。除了帮助发展基础科学，麦卡拉教授还鼓励未被充分代表的少数群体充分参与科学。作为该项目的一部分，来自詹宁斯学区和/或圣路易斯公立学区的高中生将参与一次密集的暑期研究体验。此外，来自詹宁斯学区的300多名初中生和高中生被鼓励在詹宁斯科技日活动期间追求他们对STEM职业的兴趣。烯烃被原子氧迅速氧化。这项研究的总体目标是揭示光脱氧过程、烯烃结构和局部环境如何影响氧化机理和氧化产物的分布。为了确定初始氧化步骤是通过电荷转移还是通过自由基途径发生，使用了环丙基甲醇探针、瞬时吸收光谱、动力学同位素效应和计算方法。确定初始步骤的性质对于了解条件如何影响观察到的脂质氧化产物至关重要。在膜中观察到的脂类产物预计也对原子氧释放的位置敏感。为了探索这一假说，制备了有望在脂质双层内部或外部特异性释放原子氧的原子氧前体，并确定了它们的脂氧化轮廓。虽然原子氧被一些杂环氧化物光释放，但已观察到光脱氧作用产生与原子氧无关的氧化产物。对这一机理和相关的烯烃氧化产物进行表征，拓展了光脱氧的潜在应用。从这些研究中获得的机制细节为理解光脱氧引起的脂质氧化如何影响细胞过程奠定了基础。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Structure, Dynamics and Mechanisms-B Program, Professor Ryan McCulla of Saint Louis University investigates the chemical pathways for biological oxidation. Highly reactive atomic oxygen is formed from certain ring-containing molecules when they are exposed to ultraviolet or visible light. This reaction - known as photochemical cleavage - can be carefully directed so that the atomic oxygen is formed in very specific places within biological cell membranes. Once the atomic oxygen is formed and released, it can attack carbon-carbon double bonds in other biomolecules. Knowing more about how and when light can be used to generate atomic oxygen and how this oxygen attacks other molecules (in a process called oxidative stress) may enable scientists to develop new disease therapies that are initiated by light instead of other chemicals. Oxidative stress has been associated with cardiovascular disease, diabetes, and smoking cigarettes. This research facilitates the investigation of the physiological effects on the cell membranes arising from oxidative stress. In the long term, this work may have beneficial impacts on the health and well-being of society. In addition to helping to develop fundamental science, Professor McCulla encourages the full participation of underrepresented minorities in science. As part of this project, high school students from the Jennings School District and/or the St. Louis Public School District are involved in an intensive summer research experience. Additionally, over 300 middle school and high school students from the Jennings School District are encouraged to pursue their interest in a STEM career during the Jennings Science and Technology Day activities. Alkenes are rapidly oxidized by atomic oxygen. The overall objective of this research is to reveal how the process of photo-deoxygenation, alkene structure, and local environment influence the mechanism of oxidation and the distribution of oxidized products. To determine if the initial oxidation step occurs through a charge transfer or radical pathway, cyclopropylcarbinyl probes, transient absorption spectroscopy, kinetic isotope effects, and computational methods are used. Determining the nature of the initial step is crucial to understanding how conditions influence the observed lipid oxidation products. The products observed for lipids within a membrane are also expected to be sensitive to the site of atomic oxygen release. To probe this hypothesis, atomic oxygen precursors that are expected to specifically release atomic oxygen within the interior or exterior of the lipid bilayer are prepared and their lipid oxidation profiles are determined. While atomic oxygen is photo-released by a number of heterocyclic oxides, photo-deoxygenation has been observed to generate oxidized products not associated with atomic oxygen. Characterizing this mechanism and the associated alkene oxidation products expands the potential applications of photo-deoxygenation. The mechanistic detail obtained from these studies lays a foundation for understanding how lipid oxidation by photo-deoxygenation affects cellular processes. The fundamental knowledge could be used to improve phototherapies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.