Experimental Studies of the Structures, Energetics, and Reactions of Gas Phase Self-Assembled Biomolecular Ionic Complexes

气相自组装生物分子离子配合物的结构、能量学和反应的实验研究

• 批准号: RGPIN-2014-04429
• 负责人: Fridgen, Travis
• 金额: $ 3.93万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=651180
• 关键词: Experimental; Studies; Structures; Energetics; Reactions

Studies of complexes composed of metal cations and amino acids or DNA bases are important for our understanding of the physical chemistry of self-assembled biomaterials. The structures also have biological relevance in terms of, for example, telomere research. Part of the work proposed is to study the intrinsic structures, energetics, and spectroscopy of G-tetrads that compose G-quadruplexes-tracts of guanine residues at the ends of DNA strands which are an important part of the telomere. The assembley of these G-quadruplexes are typically initiated by metal cations. 9-ethylguanine (9-eG) is an ideal model for the nucleic acid as the 9-position is blocked, as it is in nucleic acids. Preliminary experimental work on (9eG)4M+ (M=Li+, Na+, K+, and Cs+) has revealed a remarkable stability of the (9eG)4Na+ complexes which theory shows us are square planar. In contrast, complexes with the other metal ions are non-planar, probably due to competition between hydrogen bonding between the nucleic acids and metal-ion/molecule interactions. Much more work is required to fully understand the balance of intermolecular forces that bind these structures. For example, what is the effect on structure stability and reactivity of metal cations with higher oxidation states such as the alkali earth, transition, and lanthanide metals. This research will also lead to valuable information on metal ion induced defects in nucleic acids. We plan to study the structures and energetics of higher order structures such as (9eG)8M+ and [(9eG)12M2]2+ of significance to biological and supramolecular materials research. The construction of these complexes relies on molecular recognition and self-assembly processes that occur in DNA, RNA, and proteins etc. Supramolecular complexes of the other nucleic acid bases as well as those composed of a mixture of bases will be studied. This research will have an impact health and cancer research, providing fundamental knowledge of the makeup of these biological complexes.*We will carry out research on polymetallic cation-peptide supramolecular assemblies. We have done preliminary CID studies on complexes such as [Ca5(GlyGly-H)8]2+ and have also begun to model them. Our current picture has the five Ca2+ ions in a plane bridged by oxygen atoms of the peptide, similar to proposed structures of naturally occurring clusters such as ferritin and the oxygen-evolving complex of photosystem II. We propose to compare the structures, energetics and reactivities of self-assembled complexes composed of different metals and larger, varied peptides in the gas phase.*These studies will be augmented by research on smaller components of the supramolecular clusters, such as metal cation-bound dimers of amino acids, DNA bases, and carbohydrates.*A new tunable IR laser, far more powerful than our current one is on order. This laser will allow us to record IRMPD spectra on G-tetrads and other strongly-bound species which was not possible with our current laser. With this new laser, our spectral range increases down to 2400 cm-1 (from 3200 cm-1) allowing us to spectroscopically characterize the fundamentally important and very intense hydrogen bonded N-H stretching bands. Besides IRMPD spectroscopy and computational techniques to determine structures of gaseous ions we will use energy-resolved CID, CID coupled with isotopic substitution, blackbody infrared radiative dissociation coupled with master equation modeling to determine binding energies, and radiative association with kinetic modeling to study bimolecular ion-molecule reactions. We are also adding simulated annealing to our repertoire of techniques to help ensure we have explored the full geometric space of our large clusters.

金属离子与氨基酸或DNA碱基形成的配合物的研究对于我们理解自组装生物材料的物理化学具有重要意义。这些结构在例如端粒研究方面也具有生物相关性。提出的工作的一部分是研究G-四联体的内在结构，能量学和光谱学，G-四联体组成G-四链体-DNA链末端的鸟嘌呤残基束，这是端粒的重要组成部分。这些G-四链体的链节通常由金属阳离子引发。9-乙基鸟嘌呤（9-eG）是核酸的理想模型，因为9-位被封闭，就像在核酸中一样。对（9 eG）_4M ~+（M=Li ~+，Na ~+，K ~+，Cs ~+）配合物的初步实验研究表明，（9 eG）_4Na ~+配合物具有显著的稳定性。相反，与其他金属离子的配合物是非平面的，可能是由于核酸之间的氢键和金属离子/分子相互作用之间的竞争。要完全理解结合这些结构的分子间力的平衡，还需要做更多的工作。例如，什么是结构的稳定性和反应性的金属阳离子具有较高的氧化态，如碱土金属，过渡金属和镧系金属的影响。这项研究也将导致有价值的信息，金属离子诱导的核酸缺陷。我们计划研究对生物和超分子材料研究具有重要意义的高阶结构如（9 eG）8 M+和[（9 eG）12 M2]2+的结构和能量学。这些复合物的构建依赖于发生在DNA、RNA和蛋白质等中的分子识别和自组装过程。将研究其他核酸碱基的超分子复合物以及由碱基混合物组成的超分子复合物。这项研究将对健康和癌症研究产生影响，为这些生物复合物的构成提供基础知识。我们将开展多金属阳离子-肽超分子组装体的研究。我们已经对[Ca 5（GlyGly-H）8]2+等复合物进行了初步的CID研究，并开始对它们进行建模。我们目前的图片有五个Ca 2+离子在一个平面上桥接的氧原子的肽，类似于建议的结构，自然发生的集群，如铁蛋白和光系统II的氧释放复合物。我们建议比较不同金属和更大的、不同的肽在气相中形成的自组装复合物的结构、能量学和反应性。这些研究将通过对超分子团簇的较小组分的研究来增强，例如金属阳离子结合的氨基酸、DNA碱基和碳水化合物的二聚体。一种新的可调谐红外激光器，远比我们现有的更强大。这种激光器将使我们能够记录G-四分体和其他强结合物种的IRMPD光谱，这是我们目前的激光器所无法实现的。 有了这种新的激光器，我们的光谱范围增加到2400 cm-1（从3200 cm-1），使我们能够在光谱上表征根本重要和非常强烈的氢键N-H伸缩带。除了IRMPD光谱和计算技术，以确定气态离子的结构，我们将使用能量分辨CID，CID耦合同位素取代，黑体红外辐射解离耦合主方程建模，以确定结合能，并与动力学建模辐射关联研究双分子离子分子反应。 我们还将模拟退火添加到我们的技术库中，以帮助确保我们已经探索了大型集群的完整几何空间。