Redox enzymes - tuning and design

氧化还原酶 - 调整和设计

• 批准号: 10339949
• 负责人: ANASTASSIA N ALEXANDROVA
• 金额: $ 1.84万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10339949
• 关键词: Active Sites; Address; Behavior; Catalysis; Cations; Complex; Electron Spin Resonance Spectroscopy; Electron Transport; Electrons; Electrostatics; Enzymes; Exhibits; Health; Human; Hydrogen; Hydrogen Bonding; Kinetics; Measurable; Modeling; Molecular; Oxidation-Reduction; Periodicity; Play; Process; Proteins; Protons; Reaction; Regulation; Research; Schiff Bases; Spectrum Analysis; System; Techniques; Theoretical Studies; Thermodynamics; Transition Elements; X ray diffraction analysis; absorption; base; design; electric field; improved; metal complex; reaction rate; vibration

PROJECT SUMMARY Enzymes exhibit superb catalytic efficiencies and reaction selectivity. Local electric field (electrostatic) effects have been proposed as critical factors, providing stability and regulation of enzyme function and redox behavior. Within a protein, these effects are difficult to detect and control. However, molecular transition metal complexes with incorporated electrostatic interactions offer spectroscopic signatures, making these effects easier to study. In contrast to other noncovalent interactions, such as H-bonding, experimental examples of local electric field effects have been minimally explored despite theoretical studies supporting their potential to improve reaction rate, regioselectivity, and stereoselectivity at molecular systems. Of the existing state-of-the-art experimental examples of designed electric fields, several practical challenges currently limit the scalability and generality of these techniques. Therefore, the broad objective of this proposal is to develop transition metal complexes with local electric field effects and to study how modulation of the electrostatic interaction can be used to control reactivity. This research is based on the central hypothesis that incorporating cationic or anionic moieties proximal to a transition metal center will result in defined and measurable electric field effects, which can then be harnessed to tune the proton- and electron-transfer reactivity of the transition metal complex. The following specific aims will be explored: 1) Develop correlations between electric field effects at Mn, Cr and V Schiff base complexes to proton, electron, and hydrogen atom transfer reactions; and 2) Demonstrate stoichiometric O- and N-atom transfer reactions. We will use the straightforward synthesis and broad reactivity of Schiff base complexes to our advantage to study these electrostatic effects. Cyclic voltammetry, X-ray diffraction, and vibrational spectroscopy will be used to quantify the magnitude of the electric field present at the transition metal complex. Further, reactivity studies will employ electron paramagnetic resonance and UV-vis absorption spectroscopies. The product of this research will be a fundamental understanding of how electric fields play key roles in modulating reactivity of transition metals. This model will build our understanding of how enzymes exploit similar effects to achieve reaction selectivity and rate-enhancement for biosynthetic processes.

项目概要 酶表现出卓越的催化效率和反应选择性。局部电场（静电）效应 已被提议作为关键因素，提供酶功能和氧化还原行为的稳定性和调节。 在蛋白质内，这些效应很难检测和控制。然而，分子过渡金属配合物 结合静电相互作用提供光谱特征，使这些效应更容易研究。 与其他非共价相互作用（例如氢键）相比，局域电场的实验示例 尽管理论研究支持其改善反应的潜力，但对其影响的探索却很少 分子系统的速率、区域选择性和立体选择性。现有最先进的实验 设计电场的例子，目前的一些实际挑战限制了其可扩展性和通用性 这些技术。因此，该提案的总体目标是开发具有以下特征的过渡金属配合物： 局部电场效应并研究如何使用静电相互作用的调制来控制 反应性。 这项研究基于这样的中心假设：结合接近的阳离子或阴离子部分 过渡金属中心将产生明确且可测量的电场效应，然后可以对其进行利用 调节过渡金属络合物的质子和电子转移反应性。具体目标如下 将探讨： 1) 开发 Mn、Cr ​​和 V 席夫碱配合物电场效应之间的相关性 质子、电子和氢原子转移反应； 2) 展示化学计量的 O 原子和 N 原子 转移反应。我们将利用希夫碱配合物的直接合成和广泛反应性来构建我们的 研究这些静电效应的优势。循环伏安法、X 射线衍射和振动光谱 将用于量化过渡金属配合物中存在的电场的大小。更远， 反应性研究将采用电子顺磁共振和紫外可见吸收光谱。这 这项研究的成果将是对电场如何在调制中发挥关键作用的基本理解 过渡金属的反应性。该模型将帮助我们了解酶如何利用类似的效应 实现生物合成过程的反应选择性和速率提高。