Thermochemistry of Noncovalent Metal-Ligand Bonds of Biological Relevance

韦恩州立大学的Mary T. Rodgers博士因其在非共价金属-配体键的生物相关性热化学方面的研究获得了化学学部物理化学项目的资助。她将在质谱、化学反应动力学和气相离子化学领域推进她的工作，使用流管离子产生与引导离子束串联质谱（GIBMS）相结合的技术。这些进展包括：1)电喷雾电离（ESI）源的开发与离子漏斗相结合，从而能够在气相中产生非挥发性和热脆性离子，并产生多带电物质；2)对流动管和反应区的中性反应物入口进行升级改造；3)增强计算资源。本文主要研究三个相关领域：1)确定金属-配体相互作用的绝对键能；2)建立具有生物相关性的非共价金属-配体相互作用的热化学数据库；3)发展阈值碰撞诱导离解和相关方法，作为在越来越大的系统上测量精确热化学数据的手段。实验研究将得到补充理论工作的支持和加强。该计划的主要动机是使气相研究提供的详细信息与功能性生物系统的详细信息之间更好地相互关联。所采取的教学方法，即从模型系统开始，逐渐增加所研究系统的复杂性，以最大限度地提高生物聚合物热力学信息可以准确和精确地获得的可能性。金属离子参与了核酸（DNA和RNA）等生命分子参与的所有生物过程。将金属离子与核酸结合的影响从稳定分子结构到细胞死亡不等。这种效果的变化是由金属离子与核酸相互作用的几个可能的位置引起的：在磷酸主链上，在糖部分上，或在碱基上。这项工作旨在提供有关金属与核酸成分相互作用强度的基本信息，以阐明特定官能团对生物相互作用的贡献。在这项工作中，一种专门设计用于精确测定反应热化学的技术，被称为引导离子束串联质谱法，将用于检查金属离子与生物相关化学物种的相互作用。实验工作与理论的结合提供了额外的见解，也增强了预测能力。

Dr. Mary T. Rodgers of Wayne State University is funded for her research on thermochemistry of noncovalent metal-ligand bonds of biological relevance by a grant in the Physical Chemistry program of the Chemistry Division. She will advance her work in the areas of mass spectrometry, chemical reaction dynamics, and gas-phase ion chemistry using the combined techniques of flow tube ion generation coupled with guided ion beam tandem mass spectrometry (GIBMS). These advances include: 1) development of an electrospray ionization (ESI) source coupled with an ion funnel to enable production of nonvolatile and thermally fragile ions in the gas phase and production of multiply charged species; 2) construction of an upgrade of her neutral reactant inlets for both the flow tube and the reaction region; 3) enhancement of computational resources. The proposed research emphasizes three related areas: 1) the determination of absolute bond energies for metal-ligand interactions of biological relevance; 2) development of a thermochemical database of noncovalent metal-ligand interactions of biological relevance; 3) development of threshold collision-induced dissociation and related methods as means to measure accurate thermochemical data on increasingly larger systems. Experimental studies will be supported and enhanced by complementary theoretical work. A prime motivation for this program is to make better correlations between the detailed information provided by gas-phase studies with those of functional biological systems. The pedagogical approach taken, i.e. starting with model systems and gradually increasing the complexity of the systems under investigation was chosen to maximize the probability that thermodynamic information on biological polymers can be obtained with accuracy and precision. Metal ions are involved in all biological processes that nucleic acids (DNA and RNA), the molecules of life participate in. The effects of binding a metal ion to a nucleic acid vary from stabilization of the molecular structure to cell death. This variation in effect results from several possible sites where the metal ion can interact with the nucleic acid: at the phosphate backbone, at the sugar moiety, or at the base. The work is designed to provide fundamental information about the strength of the interactions of metals with the constituents of nucleic acids to elucidate the contributions of particular functional groups to bio-interactions. In this work, a technique that has been specifically designed for the accurate determination of reaction thermochemistry and known as guided ion beam tandem mass spectrometry will be utilized to examine metal ion interactions with chemical species of biological relevance. A coupling of experimental work with theory provides additional insight and also enhances predictive capabilities.