POLYAMMONIUM MACROCYCLE CATALYSIS OF PHOSPHORYL TRANSFER

本研究的重点是对黄腐酸的化学研究。 由多铵大环(受体)组成的络合物 和阴离子(底物)。初步研究表明， 在受体之间形成高亲和力的复合体 分子和磷酸盐衍生物，以及这些“超分子” 络合物“经历化学转化。显著的速率 在ATP，ADP的去磷酸化， 焦磷酸盐和甲酰磷酸盐。两个突出的特点 反应的关键是亲核催化和金属离子。 监管。 这项提议的目标是分析 聚铵大环与ATP、ADP、 焦磷酸盐和酰基磷酸盐。特异性受体 这项研究中使用的分子是范围在 大小从24个环原子到32个环原子和含有 吊坠或桥接基团。本文件所述的具体目标 建议书涉及以下内容： 1.形成复合体的亲和力和专一性， 2.活跃(生产性)和非生产性(非生产性)的结构 复合体， 3.静电催化， 4.总酸总碱催化， 5.共价(亲核)催化，以及 6.金属离子催化。 为这项研究提出的一般方法包括 PKas、稳定常数和化学计量的测定。 动力学研究将包括测定活化度。 参数、同位素掺入和手性磷酸盐分析。 结构研究将采用多核核磁共振和X射线 晶体分析。 这项研究的结果应该对设计有所帮助。 人造催化剂。此外，这些研究应提供 关于这些高能分子化学的基本信息 底物及其与酶反应的机理。

The focus of this research is the study of the chemistry of complexes consisting of polyammonium macrocycles (receptors) and anions (substrates). Preliminary studies have shown that high affinity complexes are formed between the receptor molecules and phosphate derivatives, and these "supramolecular complexes" undergo chemical transformations. Significant rate accelerations are noted in the dephosphorylation of ATP, ADP, pyrophosphate, and formyl phosphate. Two prominent features of the reaction are nucleophilic catalysis and metal ion regulation. The goal of this proposal is to analyze the chemistry of the reactions of polyammonium macrocycles with ATP, ADP, pyrophosphate, and acyl phosphates. The specific receptor molecules to be used in this study are macrocycles ranging in size from 24 to 32 ring atoms and modified rings containing pendant or bridging groups. The specific aims described in the proposal address the following: 1. affinity and specificity in complex formation, 2. structure of active (productive) and inactive (non-productive) complexes, 3. electrostatic catalysis, 4. general-acid general-base catalysis, 5. covalent (nucleophilic) catalysis, and 6. metal ion catalysis. General methodology proposed for this study includes the determination of pKas, stability constants, and stoichiometry. Kinetic studies will include the determination of activation parameters, isotope incorporation, and chiral phosphate analysis. Structural studies will employ multinuclear NMR and X-ray crystallographic analysis. The results of this research should be instrumental to the design of artificial catalysts. In addition, these studies should provide fundamental information on the chemistry of these high-energy substrates and the mechanisms of their reactions with enzymes.