A Supramolecular Coordination Cluster as a Functional Monoterpene Synthase Mimic.

描述（由申请人提供）：萜烯合酶催化级联1，5-二烯或异戊二烯环化反应，产生萜烯天然产物的碳环骨架。这些酶通过控制碳正离子的构象和局部静电环境来促进环化。单萜脱氢酶催化最简单的异戊二烯环化以形成天然产物的单萜类，其中柠檬烯合酶催化由香叶基二磷酸形成对薄荷烷亚类。带负电荷的，水溶性的，四面体配合物的雷蒙德集团提出作为柠檬烯合成酶模拟，将催化香叶基二磷酸衍生物的环化对薄荷烷单萜类化合物。该系统的发展将提供一个相对简单的模型，柠檬烯合酶的腔内环境，并产生的基板和腔之间的相互作用的物理描述，配位笼复合物催化的转换，需要构象或环境控制封装的中间体。因此，提出了复合物催化的仿生异戊二烯环化，需要两个方面的反应控制。具体地，四面体配位络合物将催化橙花醇或芳樟醇衍生的底物作为二磷酸香叶酯的替代物的环化。催化作用应该发生在疏水包封驱动的复合物的带负电荷的空腔内。结合将组织底物构象，而带负电荷的空腔稳定阳离子环化中间体。碳正离子的包封将抑制重排为对薄荷烷家族以外的单萜类化合物。该策略将提供用于通过超分子包封控制碳正离子的原理的证明，作为功能性萜烯合酶模拟物的第一个实例，并且探测简单包封作为用于催化的酶促策略。模拟酶功能不仅是验证生物化学作用模型的重要任务，而且是开发小分子催化新概念的重要任务。一个四面体，协调笼复合物提出模仿一类酶的功能，称为单萜类糖苷酶。非环状萜烯前体在复合物的带负电荷的空腔内的结合将以仿生方式催化它们的阳离子环化成单萜类化合物的对薄荷烷家族。

DESCRIPTION (provided by applicant): Terpene synthases catalyze cascading 1,5-diene, or isoprene, cyclizations to create the carbocyclic backbone of terpene natural products. These enzymes promote cyclization by controlling the conformation and local electrostatic environment of a carbenium ion. The monoterpene synthases catalyze the simplest isoprene cyclizations to form the monoterpenoid class of natural products in which limonene synthase catalyzes the formation of the p-menthane subgroup from geranyl diphosphate. The negatively charged, water-soluble, tetrahedral coordination complexes of the Raymond group are proposed as a limonene synthase mimic that will catalyze the cyclization of geranyl diphosphate derivatives to p-menthane monoterpenoids. Development of the system will provide a relatively simple model for the intracavity environment of limonene synthase and yield a physical description of the interaction between the substrate and cavity, The coordination cage complexes have catalyzed transformations that required either conformational or environmental control over encapsulated intermediates. Therefore, the complexes are proposed to catalyze a biomimetic isoprene cyclization that requires both aspects of reaction control. Specifically, the tetrahedral coordination complex will catalyze the cyclization of nerol or linalool derived substrates as surrogates for geranyl diphosphate. Catalysis should occur within the negatively-charged cavity of the complex driven by hydrophobic encapsulation. Binding will organize substrate conformation, while the negatively charged cavity stabilizes the cationic cyclization intermediates. Encapsulation of the carbenium ion will inhibit rearrangements to monoterpenoids outside of the p-menthane family. This strategy will provide a proof of principle for controlling a carbenium ion by supramolecular encapsulation, serve as the first example of a functional terpene synthase mimic, and probe simple encapsulation as an enzymatic strategy for catalysis. PUBLIC HEALTH RELEVANCE Mimicking enzyme function is an important task for not only validating biochemical models of action, but developing new concepts of small molecule catalysis. A tetrahedral, coordination cage complex is proposed to mimic the function of a class of enzymes known as the monoterpene synthases. Binding of acyclic terpene precursors within the complex's negatively-charged cavity will catalyze their cationic cyclization to the p-menthane family of monoterpenoids in a biomimetic fashion.