Thermochemistry of Noncovalent Metal-Ligand Bonds of Biological Relevance

韦恩州立大学的玛丽·T·罗杰斯博士因研究具有生物意义的非共价金属-配体键的热化学而获得化学系物理化学项目的资助。她将利用流动管离子发生与导引离子束串联质谱仪(GIBMS)相结合的技术，推进她在质谱学、化学反应动力学和气相离子化学领域的工作。这些进展包括：1)开发与离子漏斗相结合的电喷雾电离(ESI)源，以便能够在气相中产生不挥发的和热脆的离子，并产生多电荷物种；2)升级HER中性反应物入口，用于流动管和反应区；3)增强计算资源。建议的研究强调三个相关领域：1)生物相关金属-配体相互作用的绝对键能的确定；2)生物相关非共价金属-配体相互作用热化学数据库的开发；3)阈值碰撞诱导解离和相关方法的发展，作为在越来越大的系统上测量准确热化学数据的手段。实验研究将得到补充的理论工作的支持和加强。这一计划的一个主要动机是在气相研究提供的详细信息与功能生物系统的详细信息之间建立更好的相关性。所采取的教学方法，即从模型系统开始，逐步增加所研究系统的复杂性，是为了最大限度地准确和精确地获得有关生物聚合物的热力学信息的可能性。金属离子参与生命分子--核酸(DNA和RNA)参与的所有生物过程。金属离子与核酸结合的效果从稳定分子结构到细胞死亡各不相同。这种差异实际上是由金属离子与核酸相互作用的几个可能的位置造成的：在磷酸主干上，在糖基上，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，将利用一种专门为准确确定反应热化学而设计的技术，即导引离子束串联质谱学，来研究金属离子与具有生物相关性的化学物种的相互作用。实验工作与理论的结合提供了更多的洞察力，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.