NMR-spectroscopic investigations towards the reasons for selectivity in peptide catalysis

核磁共振波谱研究肽催化选择性的原因

• 批准号: 408803318
• 负责人: Professorin Dr. Christina Marie Thiele
• 金额: --
• 依托单位: Arbeitskreis Thiele
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/408803318?language=en
• 关键词: NMR; spectroscopic; investigations; towards; reasons

NMR spectroscopy is a powerful tool to obtain information on the structure and dynamics of organic, organometallic, inorganic or biomolecular compounds in solution at atomic resolution. Information about the three dimensional structure in solution can in turn be linked to activity and/or selectivity. This can also be true for catalysis, provided compounds or intermediates relevant for the catalytic cycle can be subjected to analysis at conditions as close to reality as possible. Furthermore, NMR spectroscopy allows the investigation of intermolecular interactions via a series of techniques. These are mostly based on magnetisation transfer from a ‘ligand’ to a ‘binder’ or vice versa. In drug discovery these techniques are used to search for pharmacologically relevant leads. The ‘binder’ usually is the target biomacromolecule (protein, e.g.) and the ‘ligand’ a proposed drug; in terms of catalysis this could be the catalyst and the substrate.It is proposed here to use NMR-spectroscopic methods to (further) investigate the importance of hydrogen bonds and London dispersion interactions in the kinetic resolution of trans-1,2-cycloalkane diols by a (series of) peptide catalyst(s). The Thiele and Schreiner groups showed previously that intermolecular interactions can be observed NMR-spectroscopically between catalyst and substrate for this particular system. Within this project the reasons for the extraordinary selectivity shall be investigated. The individual contributions of hydrogen bonds vs. dispersion interactions shall be tracked down NMR-spectroscopically employing different NMR spectroscopic techniques on a series of diols (exhibiting different selectivities and dispersion interaction surfaces but the same hydrogen bonding ability vs. the same dispersion interactions surfaces and different hydrogen bonding abilities). Additionally, different peptide catalysts with increasing polarizabilities of the amino acid, which mainly provides the interaction surface (so called Dispersion Energy Donating Amino Acids) shall be investigated. Applications of the methods used and developed herein to other (peptide) catalysed reactions - the enantioselective Dakin-West reaction, e.g. – shall then be envisioned.

核磁共振波谱是一种强大的工具，可以在原子分辨率上获得溶液中有机、有机金属、无机或生物分子化合物的结构和动力学信息。关于溶液中三维结构的信息可以反过来与活性和/或选择性联系起来。如果与催化循环相关的化合物或中间体可以在尽可能接近现实的条件下进行分析，则催化也是如此。此外，核磁共振波谱可以通过一系列技术来研究分子间的相互作用。这些主要是基于从“配体”到“粘合剂”的磁化转移，反之亦然。在药物发现中，这些技术用于寻找与药理学相关的线索。“粘合剂”通常是目标生物大分子（例如蛋白质），“配体”是提议的药物；在催化方面，这可以是催化剂和底物。本文建议使用核磁共振光谱方法（进一步）研究氢键和伦敦色散相互作用在（一系列）肽催化剂对反式-1,2-环烷二醇的动力学分解中的重要性。Thiele和Schreiner小组先前表明，在这种特殊体系中，催化剂和底物之间的分子间相互作用可以用核磁共振光谱观察到。在本项目中，应调查这种特殊选择性的原因。氢键与分散相互作用的个体贡献应在核磁共振光谱上采用不同的核磁共振光谱技术对一系列二醇（表现出不同的选择性和分散相互作用表面但具有相同的氢键能力与相同的分散相互作用表面和不同的氢键能力）进行追踪。此外，还研究了不同的多肽催化剂对主要提供相互作用表面的氨基酸（即“色散能供氨基酸”）极化能力的提高。将本文所使用和开发的方法应用于其他（肽）催化反应，例如对映选择性Dakin-West反应。