Chemistry of Metal Nitrosyls with Photolabile NO

无机、生物无机和有机金属化学项目的奖项支持加州大学圣克鲁斯分校的Pradip K. Mascharak教授合成新的非血红素铁、钌和锰亚硝基的研究，这些亚硝基在不同波长的光照射下会释放NO。研究这些配合物的光谱学和电子学性质，以确定促进NO光敏性的因素，并确定其结构。这些金属亚硝基的合成将利用一套指导原则和一系列在丁腈水合酶的金属结合区域后设计的配体，并通过NO结合进行光调节。此外，将对光活性和非活性金属亚硝基进行氧化还原和磁测量，以阐明在不同氧化态下结合在这些金属中心的NO的光亲和性的来源。还将进行理论计算，以进一步了解这一过程。我们将探索光诱导NO释放的机制，并测量亚硝基复合物将NO转移到各种生物相关底物（如谷胱甘肽和蛋白质）的能力。本研究旨在确定一氧化氮的化学结构和相关的电子特征，这些特征提供了一氧化氮的光敏性。这种亚硝基配合物将为生物化学家提供一种工具，通过光学光谱研究NO与血红素和非血红素蛋白的结合（和抑制）动力学。本研究结果将为无机NO供体光化学治疗药物的合成提供有价值的化学见解。本研究也提供了一个机会，让研究生和本科生在化学和生物学的界面上参与系统的目标导向的研究。

The award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports research by Professor Pradip K. Mascharak at the University of California at Santa Cruz to synthesize new non-heme iron, ruthenium and manganese nitrosyls that will release NO upon illumination at various wavelengths of light. The spectroscopic and electronic properties of these complexes will be explored in order to determine what factor(s) promote the photolability of NO and their structures will be determined. A set of guiding principles and a series of ligands designed after the metal-binding domain of the enzyme nitrile hydratase, which is photoregulated through NO binding, will be utilized in the syntheses of these metal nitrosyls. In addition, redox and magnetic measurements will be performed on both photoactive and inactive metal nitrosyls to elucidate the origin of the photolability of NO bound at these metal centers in different oxidation states. Theoretical calculations will also be performed to gather further insight into this process. The mechanisms of the light-induced NO release will be explored and the capacities of the nitrosyl complexes to transfer NO to various biologically relevant substrates, such as glutathione and proteins, will be measured. This research aims at identifying the chemical architectures and the associated electronic features that provide for the photolability of NO. Such nitrosyl complexes will provide the biochemists with a tool to study the kinetics of NO binding (and inhibition) to heme and non-heme proteins by optical spectroscopy. The results of this research work will provide valuable chemical insights toward syntheses of inorganic NO donors as photochemotherapeutics. This research also provides an opportunity for graduate and undergraduate students to participate in systematic goal-oriented research at the interface of chemistry and biology.