Dynamics of Small Molecules in Supramolecular Systems

超分子系统由分子结构单元可逆地形成。我的研究重点是理解超分子系统的动力学。我在方法学开发方面有很好的记录，从广泛的结构-动力学关系研究中获得了机械理解。所获得的基础知识对如何使用功能性超分子系统产生影响，并将帮助其他人合理设计功能性系统，如药物递送，催化和传感。 拟议的工作重点是不同程度的复杂性，从高度动态的超分子聚集体（胆汁盐），复杂的分子环境（蛋白质），简单的分子系统（葫芦[n]脲）的主机系统。 - 胆盐聚集体具有不同的结合位点。结构动力学研究将扩展到调查内聚集体的流动性在高客载。一个新的方向将采取的研究从溶液到凝胶中的受限空间，因为许多应用的超分子系统将需要限制在表面或固体。 - 蛋白质以非常不同的亲和力在多个位点结合客人。我们表明，当试剂以中等亲和力结合到蛋白质位点时，双分子反应的期望反应性最高，这不是通常预期的趋势。将应用光物理技术专门处理反应性最强部位的试剂。需要新的方法，因为传统的技术，如X射线晶体学，不提供的信息结合到中等亲和力网站的试剂。 - 葫芦[n]脲是以非常高的结合常数结合客体的主体，这与在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未完全了解。关于客体与葫芦[n]脲结合的动态信息目前是有限的。结构动力学关系的研究，提出了一个全面的机制的理解客体@葫芦[n]脲系统。

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.