Dynamics of Small Molecules in Supramolecular Systems

超分子系统中小分子的动力学

• 批准号: 121389-2012
• 负责人: Bohne, Cornelia
• 金额: $ 5.1万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=569184
• 关键词: Dynamics; Small; Molecules; Supramolecular; Systems

Supramolecular systems form reversibly from molecular building blocks. My research focuses on understanding the dynamics of supramolecular systems. I have a strong track record in methodology development, and mechanistic understanding is gained from extensive structure-dynamics relationship studies. The fundamental knowledge obtained has impact on how functional supramolecular systems are employed and will aid others in the rational design of functional systems, such as drug delivery, catalysis and sensing. The proposed work focuses on host systems with varying degrees of complexity, ranging from highly dynamic supramolecular aggregates (bile salts), to complex molecular environments (proteins), to simple molecular systems (cucurbit[n]urils). - Bile salt aggregates have different binding sites. Structure-dynamics studies will be extended to investigate intra-aggregate mobility at high guest loading. A new direction will take studies from solution to confined spaces in gels since many of the applications of supramolecular systems will require confinement on surfaces or solids. - Proteins bind guests in multiple sites with very different affinities. We showed that the desired reactivity for a bimolecular reaction was highest when the reagents were bound to protein sites with moderate affinity, which is not the generally expected trend. Photophysical techniques will be applied to specifically address reagents in the most reactive sites. New methodologies are required because traditional techniques, such as X-Ray crystallography, do not provide information on the reagents bound to moderate affinity sites. - Cucurbit[n]urils are hosts that bind guests with very high binding constants, which rival those observed for biological systems. The reasons for these high binding constants are not fully understood. Dynamic information on the guest binding to cucurbit[n]urils is currently limited. Structure-dynamics relationship studies are proposed to provide a comprehensive mechanistic understanding on guest@cucurbit[n]uril systems.

超分子系统由分子构件可逆地形成。我的研究重点是了解超分子系统的动力学。我在方法论开发方面拥有良好的记录，并且从广泛的结构-动力学关系研究中获得了对机理的理解。所获得的基础知识对功能性超分子系统的使用方式有影响，并将帮助其他人合理设计功能性系统，例如药物输送、催化和传感。 拟议的工作重点关注具有不同复杂程度的宿主系统，从高度动态的超分子聚集体（胆盐）到复杂的分子环境（蛋白质），再到简单的分子系统（葫芦[n]urils）。 - 胆汁盐聚集体具有不同的结合位点。结构动力学研究将扩展到研究高客体负载下聚集体内的迁移率。新的方向将把研究从溶液转向凝胶中的有限空间，因为超分子系统的许多应用需要限制在表面或固体上。 - 蛋白质以非常不同的亲和力在多个位点结合客体。我们表明，当试剂以中等亲和力结合到蛋白质位点时，双分子反应所需的反应性最高，这不是普遍预期的趋势。光物理技术将应用于专门处理最具反应性位点的试剂。需要新的方法，因为 X 射线晶体学等传统技术无法提供与中等亲和力位点结合的试剂的信息。 - 葫芦[n]脲是以非常高的结合常数结合客体的宿主，其与生物系统中观察到的结合常数相媲美。这些高结合常数的原因尚不完全清楚。目前，有关访客绑定到 cucurbit[n]urils 的动态信息有限。提出结构-动力学关系研究，以提供对 guest@cucurbit[n]uril 系统的全面机械理解。