Contra-Thermodynamic Catalysis and Fluorine Sculpting; Two Counter Cultural Approaches to Synthesis

反热力学催化和氟塑化；

• 批准号: 10544762
• 负责人: Jimmie Dean Weaver
• 金额: $ 36.17万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10544762
• 关键词: Behavior; Biology; Blushing; Catalysis; Chemicals; Development; Disparate; Elements; Energy Transfer; Fluorine; Future; Growth; Health; Human; Human body; Light; Location; Medicine; Methods; Microscopic; Periodicals; Pharmacologic Substance; Photons; Play; Process; Property; Pump; Reaction; Resources; Role; System; Thermodynamics; Triplet Multiple Birth; Visible Radiation; biological development; biological systems; catalyst; cost; innovation; interest; neglect; public health relevance; spatiotemporal; tool; tool development

Project Summary/Abstract The objectives of this proposal are two-fold and include the development and conceptual advancement of contra- thermodynamic catalysis and fluorine sculpting. The realization of both objectives will elevate the field of synthesis and positively impact human health through the development of tools for synthesis and chemical biology. While at first blush the directions appear disparate, they both rely heavily on visible light photocatalysis. However, they deviate from one another in the manner in which the excited state photocatalyst is quenched. One by triplet sensitization (Dexter energy transfer), and the other by SET to or from an excited state catalyst. Traditional catalysis has the effect of lowering energy barriers and facilitating reactions but ultimately does not alter the thermodynamics (or spontaneous direction) of the reaction. Our long term objectives are to develop strategies to realize a system that makes formerly impossible, or endergonic, synthesis possible in addition to enabling exergonic synthesis. Achieving this objective, will result in new tools for the study of large molecules, new synthetic methods. Achieving this objective will require the development of reactions which are not subject to the principles of microscopic reversibility, i.e. irreversible reactions that can serve to pump energy into the system, and the ability to harness and store the energy thermodynamic currency that can be used to drive reactions. More tangibly we seek to leverage the cis-to-trans photoisomerization of cycloalkenes to: identify energy pumping reactions, define an energetic currency, and develop strategies to spend the energetic currency to drive reactions that would be otherwise impossible. Realizing these objectives is expected to both enable synthesis via the development of new endergonic (neglecting the photon energy) reactions and methods as well as the development of biological tools that capitalize on the available energy and the spatio-temporal controlled associated with light activated processes. The second direction of this proposal also involves an unorthodox approach to synthesis. Like no other element, fluorine has the ability to modulate the properties of a molecule and its behavior within the human body. Fluorine incorporation into pharmaceuticals has seen exponential growth in recent years, and yet our synthetic capability to obtain organofluorines is surprisingly limited. Owing to fluorine’s location on the periodic table, the selective installation of C–F bonds are exceptionally challenging. Fluorine sculpting is an alternative approach to organofluorine synthesis that begins with a low cost perfluoroarene and selectively carves out the desired high-value organofluorine. It has shown great promise; providing rapid access to organofluorines. Our long term objective is to advance the concept of fluorine sculpting and provide expanded access to organofluorines of unprecedented structural complexity. This newfound ability is expected to result in greater understanding of the role fluorine plays in molecules of interest to human health.

项目概要/摘要 该提案的目标有两个，包括对立的发展和概念推进。 热力学催化和氟雕刻这两个目标的实现将提升合成和合成领域的水平。 乍一看，通过开发合成和化学生物学工具对人类健康产生积极影响。 方向看起来不同，它们都严重依赖可见光光催化，但是，它们偏离了一个方向。 另一种是通过三重态敏化（德克斯特能量）猝灭激发态光催化剂。 转移），另一个通过 SET 往返于激发态催化剂。 传统催化具有降低能垒、促进反应的作用，但最终并没有改变反应的性质。 我们的长期目标是制定实现反应的热力学（或自发方向）的策略。 除了实现放能合成之外，该系统还使以前不可能的合成或吸能合成成为可能。 实现这一目标将产生用于研究大分子的新工具和新的合成方法。 目标将需要发展不受微观可逆性原理约束的反应，即 可以将能量泵入系统的不可逆反应，以及利用和存储能量的能力 我们寻求更切实地利用顺式到反式的热力学货币。 环烯烃的光异构化：识别能量泵反应，定义能量货币，并开发 策略是花费精力充沛的货币来推动否则不可能实现的目标。 预计将通过开发新的吸能（忽略光子能量）反应来实现合成，并且 方法以及利用可用能量和时空的生物工具的开发 与光激活过程相关的控制。 该提案的第二个方向还涉及一种与其他元素不同的非正统合成方法。 能够调节分子的特性及其在人体内的行为。 近年来，制药业呈指数级增长，但我们获得有机氟的合成能力 由于氟在元素周期表中的位置，C-F键的选择性安装受到限制。 氟雕刻是有机氟合成的一种替代方法，其起始温度较低。 成本全氟芳烃并选择性地开发出所需的高价值有机氟，这已显示出巨大的前景； 我们的长期目标是推进氟塑的概念并提供。 这种新发现的能力有望扩大对具有前所未有的结构复杂性的有机氟的获取。 更好地了解氟在与人类健康相关的分子中所扮演的角色。