Mechanism of Alkene Oxidation by Photodeoxygenation

光脱氧烯烃氧化机理

• 批准号: 1900417
• 负责人: Ryan McCulla
• 金额: $ 44万
• 依托单位: Saint Louis University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1900417&HistoricalAwards=false
• 关键词: Mechanism; Alkene; Oxidation; Photodeoxygenation

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.

在化学结构、动力学和机理b项目的支持下，圣路易斯大学的Ryan McCulla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，会形成高活性的氧原子。这种被称为光化学裂解的反应可以被小心地引导，这样原子氧就会在生物细胞膜的特定位置形成。一旦氧原子形成并释放，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氧原子，以及氧原子如何攻击其他分子（在一个称为氧化应激的过程中），可能使科学家们能够开发出由光而不是其他化学物质引发的新的疾病疗法。氧化应激与心血管疾病、糖尿病和吸烟有关。本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之外，麦卡拉教授还鼓励未被充分代表的少数民族充分参与科学。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参与了一个密集的暑期研究经历。此外，詹宁斯学区的300多名中学生和高中生被鼓励在詹宁斯科技日活动中追求他们对STEM职业的兴趣。烯烃被氧原子迅速氧化。本研究的总体目的是揭示光脱氧过程、烯烃结构和局部环境如何影响氧化机制和氧化产物的分布。为了确定初始氧化步骤是通过电荷转移还是自由基途径发生，使用了环丙基碳基探针、瞬态吸收光谱、动力学同位素效应和计算方法。确定初始步骤的性质对于理解条件如何影响观察到的脂质氧化产物至关重要。在膜内观察到的脂质产物也预计对原子氧释放的位置敏感。为了验证这一假设，制备了有望在脂质双分子层内部或外部特异性释放原子氧的原子氧前体，并确定了它们的脂质氧化谱。虽然原子氧是由许多杂环氧化物光释放的，但光脱氧已被观察到产生与原子氧无关的氧化产物。表征这一机制和相关的烯烃氧化产物扩大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脂质氧化如何影响细胞过程奠定了基础。这些基础知识可用于改进光疗法。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Reactions of sulfenic acids with amines, thiols, and thiolates studied by quantum chemical calculations

通过量子化学计算研究次磺酸与胺、硫醇和硫醇盐的反应

• DOI: 10.1016/j.comptc.2020.112979
• 发表时间: 2020
• 期刊: Computational and Theoretical Chemistry
• 影响因子: 2.8
• 作者: Petroff, John T.;Omlid, Sara M.;Haloi, Nandan;Sith, Louis;Johnson, Shaquina;McCulla, Ryan D.
• 通讯作者: McCulla, Ryan D.

Effects of photodeoxygenation on cell biology using dibenzothiophene S-oxide derivatives as O(3P)-precursors

• DOI: 10.1007/s43630-021-00136-5
• 发表时间: 2021-11-25
• 期刊: PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
• 影响因子: 3.1
• 作者: Isor, Ankita;O'Dea, Austin T.;McCulla, Ryan D.
• 通讯作者: McCulla, Ryan D.

Synthesis of triphenylphosphonium dibenzothiophene S-oxide derivatives and their effect on cell cycle as photodeoxygenation-based cytotoxic agents

三苯基鏻二苯并噻吩S-氧化物衍生物的合成及其作为光脱氧细胞毒剂对细胞周期的影响

• DOI: 10.1016/j.bioorg.2020.104442
• 发表时间: 2020
• 期刊: Bioorganic Chemistry
• 影响因子: 5.1
• 作者: Isor, Ankita;O'Dea, Austin T.;Petroff, John T.;Skubic, Kristin N.;Grady, Scott F.;Arnatt, Christopher K.;McCulla, Ryan D.
• 通讯作者: McCulla, Ryan D.

Dibenzothiophene Sulfone Derivatives as Plasma Membrane Dyes

作为质膜染料的二苯并噻吩砜衍生物

• DOI: 10.1111/php.13175
• 发表时间: 2019
• 期刊: Photochemistry and Photobiology
• 影响因子: 3.3
• 作者: Petroff, II, John T.;Grady, Scott;Arnatt, Christopher K.;McCulla, Ryan D.
• 通讯作者: McCulla, Ryan D.

Visible light‐induced photodeoxygenation of polycyclic selenophene Se ‐oxides

可见光诱导多环硒酚硒氧化物的光脱氧

• DOI: 10.1002/poc.4144
• 发表时间: 2020
• 期刊: Journal of Physical Organic Chemistry
• 影响因子: 1.8
• 作者: Chintala, Satyanarayana M.;Throgmorton, John C.;Maness, Peter F.;McCulla, Ryan D.
• 通讯作者: McCulla, Ryan D.