Transient Intermediates in Electron and Proton Transfer

电子和质子转移中的瞬态中间体

• 批准号: 0750048
• 负责人: Frantisek Turecek
• 金额: $ 40.62万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0750048&HistoricalAwards=false
• 关键词: Transient; Intermediates; Electron; Proton; Transfer

With the support of an award from the Organic and Macromolecular Chemistry Program, Professor Franticek Turecek will address highly reactive molecules, radicals, and cation-radical intermediates that are produced by electron transfer to and deprotonation of cations derived from polar molecules such as peptides, nucleosides, and transition metal complexes. The knowledge gained from the proposed studies will be used to explain the reactivity of transient species relevant to electron-ion and ion-ion recombination processes in biomolecules of current interest and to formulate specific and general mechanisms governing the stability and unimolecular dissociations of a variety of highly reactive and elusive species. The proposed studies of reactive intermediates will employ experimental methods allowing for femtosecond collisional electron transfer in beam experiments, as well as electron capture in isolated ions trapped in electrostatic and magnetic fields. Special model compounds will be synthesized to separate intramolecular interactions by restricting the peptide ion conformational space. Fixed-charge groups will be used to control the energetics of electron attachment and transfer and thus to affect the electronic state(s) that are accessed by ion-electron recombination and collisional electron transfer. Ab initio computational methods will be employed to provide relative, dissociation, and transition state energies to be used for RRKM calculations of unimolecular dissociation and isomerization rate constants. Intellectual meritThe proposed research addresses fundamental and hitherto unresolved questions regarding the dissociations of peptide radicals and cation-radicals. Experiments are proposed that will permit the study of unimolecular dissociations of these transient species on a range of short time scales and under conditions of electron attachment and femtosecond collisional transfer. Electron structure theory calculations are an integral part of the proposed research in both experiment planning and data interpretation.Broader impactsPeptide radicals and cation-radicals have been of considerable interest due to their role as intermediates in mass spectrometric analytical methods for peptide sequencing and detection of protein post-translational modifications. Applications of these methods extend to biology, medicine, and other life sciences, and have been fueled by the availability of commercial instruments for electron capture dissociation and electron transfer dissociation. However, fundamental understanding of the chemistry of transient peptide cation-radicals is essential for the rational use of electron-based methods for peptide and protein sequencing. Studies of ion discharge and immobilization on metal-oxide surfaces have already brought practical results in procedures for the manufacturing of special surfaces for medical implants and selective mass spectrometric detection of phosphopeptides. The proposed research in this area is aimed at gaining insight into the processes leading to biomolecule discharge and immobilization on surfaces.

在有机化学和高分子化学项目的支持下，Francek Turecek教授将介绍高活性分子、自由基和阳离子自由基中间体，这些中间体是由来自极性分子的阳离子(如多肽、核苷和过渡金属络合物)的电子转移和去质子化而产生的。从拟议的研究中获得的知识将被用来解释与当前感兴趣的生物分子中的电子-离子和离子-离子复合过程相关的瞬时物种的反应性，并制定控制各种高活性和难以捉摸的物种的稳定性和单分子解离的具体和一般机制。拟议的活性中间体研究将采用实验方法，允许在电子束实验中进行飞秒碰撞电子转移，以及在静电场和磁场中捕获孤立离子中的电子。将合成特殊的模型化合物，通过限制多肽离子的构象空间来分离分子内的相互作用。固定电荷基团将被用来控制电子附着和转移的能级，从而影响离子-电子复合和碰撞电子转移所获得的电子态(S)。从头算方法将被用来提供相对、离解和过渡态能量，用于单分子离解和异构化速率常数的RRKM计算。智力价值拟议的研究解决了有关肽自由基和阳离子自由基解离的基本问题和迄今尚未解决的问题。建议的实验将允许在短时间范围内以及在电子附着和飞秒碰撞转移的条件下研究这些瞬变物种的单分子解离。电子结构理论计算是拟议的实验计划和数据解释中不可或缺的一部分。更广泛的影响由于肽自由基和阳离子自由基在多肽测序和蛋白质翻译后修饰检测的质谱分析方法中作为中间体的作用，因此引起了人们的极大兴趣。这些方法的应用扩展到生物、医学和其他生命科学，并因可用于电子俘获解离和电子转移解离的商业仪器而得到推动。然而，对瞬时肽阳离子自由基化学的基本了解对于合理使用基于电子的方法进行肽和蛋白质测序是必不可少的。离子放电和金属氧化物表面固定化的研究已经在医用植入物的特殊表面的制造和磷酸肽的选择性质谱学检测过程中取得了实用的结果。建议在这一领域的研究旨在深入了解导致生物分子放电和表面固定化的过程。