MOLECULAR RECOGNITION IN BIOMIMETIC RECEPTORS

这项建议描述了人工受体的发展 具有生物学意义的分子的选择性络合和 基于过渡态的新型仿生催化剂的设计 稳定状态。我们的方法将利用结合氢键， 静电和疏水相互作用以保持较强的结合 有机和水溶液。对结构也进行了详细的分析 因为这些体系的热力学和动力学性质将导致 加深了对一系列分子间相互作用的理解 溶剂型环境。在设计与之互补的受体 假设的过渡态结构，我们不仅希望开发出新的 仿生催化剂，还可以用来探测，精度是不可能的 自然体系，详细介绍了催化剂的反应机理。 受体的一个重要应用将是在构建 分子选择性传感器。 我们的具体目标包括设计、综合和评估 关键的第二信使肌醇1，4，5-的人工受体 三磷酸。我们将使用三？结合部位，并将 研究厌恶溶剂效应和pi-2的相对重要性。 装订中的堆叠方向。将采取类似的方法来 对其他关键碳水化合物的认识，包括唾液酸和 肌醇。作为这项工作的一部分，我们将研究聚磷酸二酯 作为一类新型的水溶性氢键受体。一秒钟 主要领域将是合成受体作为催化剂的开发 基于密钥转移的选择性识别与稳定化 国家结构。我们将重点关注几种反应，包括 分支酸的重排以预苯化。我们将准备一个家庭 分支酸受体能够与不同构象的 二元酸沿着反应路径。动力学效应的分析 主机将允许我们确定最优的绑定安排 稳定过渡态。静电组也将被 潜在地整合到受体中，以评估它们在 催化机理。这一策略也将应用于其他 包括Claisen重排和Cope重排的反应及顺反反应 酰胺键的异构化。

This proposal describes development of artificial receptors for the selective complexation of biologically significant molecules and the design of new biomimetic catalysts based on transition state stabilization. Our approach will exploit combined hydrogen bonding, electrostatic and hydrophobic interactions to maintain strong binding in organic and aqueous solvent. Detailed analysis of the structure as well as thermodynamic and kinetic properties of these systems will lead to increased understanding of intermolecular interactions in a range of solvent environments. In designing receptors that are complementary to postulated transition state structures we hope not only to develop new biomimetic catalysts but also to probe, with a precision not possible in the natural system, details of the reaction mechanism of the catalysts. An important application of the receptors will be in the construction of molecule-selective sensors. Our specific aims include the design, synthesis and evaluation of artificial receptors for the key second messenger, inositol 1,4,5- trisphosphate. We will use a tris-guanidinium binding site and will investigate the relative importance of solvophobic effects and pi- stacking orientations in binding. A similar approach will be taken to the recognition of other key carbohydrates including sialic acid and inositol. As part of this work we will investigate polyphosphodiesters as a novel class of water soluble, hydrogen bonding receptors. A second major area will be the development of synthetic receptors as catalysts based on the selective recognition and stabilization of key transition state structures. We will focus on several reactions including the rearrangement of chorismate to prephenate. We will prepare a family of chorismate receptors capable of binding to different conformations of the diacid along the reaction pathway. Analysis of the kinetic effects of the hosts will allow us to determine the optimal binding arrangement for stabilizing the transition state. Electrostatic groups will also be incorporated into the receptor potentially to assess their role in the catalytic mechanism. This strategy will also be applied to other reactions including the Claisen and Cope rearrangements and the cis-trans isomerization of amide bonds.