POLYAMMONIUM MACROCYCLE CATALYSIS OF PHOSPHORYL TRANSFER

本研究的重点是研究的化学 由多铵大环化合物（受体）组成的复合物 和阴离子（底物）。 初步研究表明， 在受体之间形成高亲和力复合物 分子和磷酸盐衍生物，这些“超分子” 复合物”经历化学转变。 费率显著 ATP，ADP， 焦磷酸和甲酰磷酸。 两个突出特点 亲核催化和金属离子 调控 该提案的目标是分析 聚铵大环与ATP，ADP， 焦磷酸和酰基磷酸。 特异性受体 本研究中使用的分子是大环化合物， 尺寸为24至32个环原子和含有以下的改性环： 侧基或桥连基团。 报告中所述的具体目标 建议涉及以下方面： 1. 在复合物形成中的亲和力和特异性， 2. 活跃（生产性）和非活跃（非生产性）结构 络合物， 3. 静电催化， 4. 通用酸通用碱催化， 5. 共价（亲核）催化，和 6. 金属离子催化 为这项研究提出的一般方法包括： 测定pKa、稳定常数和化学计量。 动力学研究将包括确定活化 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 晶体学分析 本研究的结果应有助于设计 人工催化剂。 此外，这些研究应提供 关于这些高能化学的基本信息 底物及其与酶反应的机制。

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.