Redox enzymes - tuning and design

项目总结 酶表现出极高的催化效率和反应选择性。局部电场(静电)效应 已经被认为是提供酶功能和氧化还原行为的稳定和调节的关键因素。 在蛋白质中，这些效应很难检测和控制。然而，分子过渡金属配合物 结合了静电相互作用提供了光谱特征，使这些效应更容易研究。 与其他非共价相互作用，如氢键，局部电场的实验例子 尽管理论研究支持它们改善反应的潜力，但对其影响的探索却很少。 分子体系的速率、区域选择性和立体选择性。现有的最先进的实验 设计的电场的例子，几个实际挑战目前限制了可伸缩性和一般性 这些技巧。因此，这项提议的广泛目标是开发具有以下特征的过渡金属配合物 研究如何利用静电相互作用的调制来控制局部电场效应 反应性。 这项研究是基于一个中心假设，即在近端加入阳离子或阴离子部分 过渡金属中心将产生明确的、可测量的电场效应，然后可以加以利用。 调整过渡金属络合物的质子和电子转移反应性。以下是具体目标 将探索：1)建立锰、铬和钒希夫碱配合物的电场效应之间的关联，以 质子、电子和氢原子转移反应；以及2)显示化学计量比的O原子和N原子 转移反应。我们将利用席夫碱配合物的直接合成和广泛的反应性来 有利于研究这些静电效应。循环伏安法、X射线衍射法和振动光谱 将用于量化过渡金属络合物中存在的电场的大小。此外， 反应性研究将使用电子顺磁共振和UV-Vis吸收光谱。这个 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。这个模型将建立我们对酶如何利用类似于 实现生物合成过程的反应选择性和速率提高。

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.