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

项目摘要/摘要 铁-硫团簇几乎存在于所有形式的生命中，在这些生命中，它们是许多生命所必需的金属辅因子。 关键的生物过程。尽管几十年的联合研究努力，但复杂的电子 这些团簇的结构转化为它们独特的反应性仍然不清楚。这个问题的核心是， 尤其是当它与高核度团簇有关时，它表征了价电子的分布 这些无处不在的金属辅因子的基态和低激发态的水平，这一挑战需要位置- 大的交换耦合团簇中单个顺磁性铁离子的特定特征数据。在此 我们提出了一种克服这一挑战的方法，通过对合成和合成的 生物铁-硫团簇。这项建议的主要目的是利用这一战略来描述 原子分辨率下[Fe4S4]团簇的价电子结构。 铁硫团簇的电子结构的最大特点是存在致密的 许多近乎简并的、热可达的电子态的流形。这一现象的一个重要后果 电子结构是低激发态的可用性，在低激发态中，位点价的空间排列 不同于基态(“价异构体”)。而铁-S星团对这些多样性样本的能力 电子态被认为在它们的反应性、直接的、实验的表征中起作用。 电子态是缺乏的。在此，我们提出了一种同步测量的研究策略 用穆斯堡尔谱研究[Fe4S4]团簇在基态和低激发态的位置价态 通过位点选择性的57Fe标记实现。通过对一系列合成的和蛋白质结合的 [Fe4S4]团簇，具有可变的主配位和次配位，我们可以开始描绘 这些无处不在的化合物的动态价电子结构的结构-功能关系 金属辅因子。 这里开发的方法将允许首次表征这些分子的低能激发态 具有站点特定分辨率的集群。此外，这些方法还可以扩展到其他示例 生物铁-硫簇，如新出现的自由基S-腺苷蛋氨酸超家族中的那些。这个 根据本奖项设计的培训计划将使申请者具备过渡到 研究金属在生物学中的作用的独立职业，通过完成拟议的研究，如 以及获得该领域初级和高级研究人员的赞助。最后，活动 在此奖学金下计划的研究将受益于由 麻省理工学院。

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.