Primary and Secondary Sphere Effects on the Valence Isomerism of Fe-S Clusters

项目总结/摘要 铁硫簇存在于几乎所有的生命形式中，它们是许多生命的重要金属辅因子。 关键的生物过程。尽管经过几十年的联合研究，复杂的电子 这些团簇的结构转化为其独特的反应性仍然不清楚。这个问题的核心是， 特别是当它涉及到高核性的集群，是表征电子在价态分布 这些无处不在的金属辅因子的基态和低位激发态的水平，这是一个需要位点- 在一个大的交换耦合簇内的单个顺磁性Fe离子的具体表征数据。本文 我们提出了一种方法，通过合成和合成的位点特异性标记来克服这一挑战， 生物铁硫团簇本提案的主要目的是利用这一战略来表征 [Fe_4S_4]团簇的价电子结构及其原子分辨率。 铁硫团簇电子结构的最显著特征是存在致密的 许多近简并的、热可及的电子态的流形。一个重要的后果是 电子结构是低位激发态的可用性，其中位置价的空间排列 不同于基态（“价态异构体”）。虽然Fe-S簇对这些不同的样品的能力 电子状态被假定在它们的反应性中起作用，直接，实验表征这些 缺乏电子国家。在这里，我们提出了一个研究策略，同时测量的 通过穆斯堡尔谱学研究[Fe 4S 4]团簇在基态和低激发态的位置价态， 通过位点选择性57 Fe标记实现。通过对一系列合成的和蛋白质结合的 [Fe 4S 4]簇，具有可变的初级和次级配位球，我们可以开始描绘 这些无处不在的动力学价电子结构的结构-功能关系 金属辅因子 本文开发的方法将允许这些化合物的低能量激发态的第一个表征。 具有站点特定分辨率的群集。此外，这些方法可以被扩展到其他示例。 生物铁硫簇，如新兴的自由基S-腺苷甲硫氨酸超家族中的那些。的 根据该奖项设计的培训计划将使申请人具备必要的技能， 独立的职业生涯研究金属在生物学中的作用，无论是通过完成拟议的研究， 以及确保该领域初级和高级研究人员的赞助。最后，活动 根据这项奖学金计划将受益于世界一流的研究环境所提供的 马萨诸塞州理工学院。

PROJECT SUMMARY/ABSTRACT Iron–sulfur clusters are found in nearly all forms of life, where they serve as essential metallocofactors for many critical biological processes. Despite decades of combined research efforts, just how the complex electronic structures of these clusters translate into their unique reactivity remains obscure. Central to this problem, especially as it pertains to clusters of high nuclearity, is characterizing the distribution of electrons at the valence level in the ground and low-lying excited states of these ubiquitous metallocofactors, a challenge requiring site- specific characterization data of individual paramagnetic Fe ions within a large exchange-coupled cluster. Herein we propose an approach toward overcoming this challenge via the site-specific labeling of synthetic and biological iron–sulfur clusters. The primary aim of this proposal is to exploit this strategy to characterize the valence electronic structure of [Fe4S4] clusters with atomic resolution. The most distinguishing feature of the electronic structures of iron–sulfur clusters is the presence of a dense manifold of many nearly-degenerate, thermally-accessible electronic states. An important consequence of this electronic structure is the availability of low-lying excited states in which the spatial arrangement of site valences differs from that of the ground state (“valence isomers”). While the ability of Fe–S clusters to sample these diverse electronic states is postulated to play a role in their reactivity, direct, experimental characterization of these electronic states is lacking. Herein, we propose a research strategy for the simultaneous measurement of the site valences of [Fe4S4] clusters in their ground and low-lying excited states via Mössbauer spectroscopy, enabled via site-selective 57Fe labeling. By performing these studies on a range of synthetic and protein-bound [Fe4S4] clusters, with variable primary and secondary coordination spheres, we can begin to delineate the structure-function relationships that underlie the dynamical valence electronic structure of these ubiquitous metallocofactors. The approaches developed herein will allow for the first characterization of the low-energy excited states of these clusters with site-specific resolution. Moreover, these approaches may be extended to other examples of biological iron–sulfur clusters, such as those in the emergent radical S-adenosylmethionine superfamily. The training plan designed under this award will equip the applicant with the skills necessary to transition to an independent career studying the roles of metals in biology, both via accomplishing the proposed research, as well as by securing the sponsorship of both junior and senior researchers in the field. Finally, the activities planned under this fellowship will benefit from the world-class research environment provided by the Massachusetts Institute of Technology.