Redox enzymes - tuning and design

项目摘要 酶具有极好的催化效率和反应选择性。局部电场（静电）效应 已被提出作为关键因素，提供稳定性和酶功能和氧化还原行为的调节。 在蛋白质中，这些效应很难检测和控制。然而，分子过渡金属络合物 与合并的静电相互作用提供光谱特征，使这些效果更容易研究。 与其他非共价相互作用（如氢键）相比，局部电场的实验示例 尽管理论研究支持其改善反应的潜力， 速率、区域选择性和立体选择性。现有的最先进的实验 尽管已经描述了设计电场的示例，但是当前的几个实际挑战限制了本发明的可扩展性和通用性。 这些技术。因此，本提案的广泛目标是开发具有以下性质的过渡金属络合物： 局部电场效应，并研究如何调制的静电相互作用可以用来控制 反应性 这项研究是基于中心假设，将阳离子或阴离子部分接近 过渡金属中心将产生确定的和可测量的电场效应，然后可以利用这些电场效应。 以调节过渡金属络合物的质子和电子转移反应性。以下具体目标 将探索：1）开发Mn，Cr和V Schiff碱络合物的电场效应之间的相关性， 质子、电子和氢原子转移反应; 2）演示化学计量的O-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研究我们的 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 将用于量化存在于过渡金属络合物处的电场的大小。此外，本发明还 反应性研究将采用电子顺磁共振和紫外-可见吸收光谱。的 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效应的理解， 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.