A Supramolecular Coordination Cluster as a Functional Monoterpene Synthase Mimic.

描述（由申请人提供）：萜烯合成酶催化级联1,5-二烯或异戊二烯环化，以产生萜烯天然产物的碳环骨架。这些酶通过控制碳离子的构象和局部静电环境来促进环化。单萜合成酶催化最简单的异戊二烯环化形成单萜类天然产物，其中柠檬烯合成酶催化香叶烯二磷酸形成对甲烷亚基。带负电的水溶性四面体雷蒙德基团配位配合物被认为是柠檬烯合成酶的模拟物，可以催化香叶基二磷酸衍生物环化成对甲烷单萜。该系统的开发将为柠檬烯合成酶的腔内环境提供一个相对简单的模型，并对底物和腔之间的相互作用进行物理描述。配位笼配合物催化了需要对封装中间体进行构象或环境控制的转化。因此，提出了配合物催化仿生异戊二烯环化，需要两个方面的反应控制。具体来说，四面体配位配合物将催化橙酚或芳樟醇衍生底物的环化，作为二磷酸香叶基的替代品。催化作用应发生在疏水包封驱动的带负电荷的络合物腔内。结合将组织底物构象，而带负电荷的腔稳定阳离子环化中间体。正碳离子的包封会抑制对甲烷家族以外的单萜的重排。该策略将为通过超分子包封控制碳离子提供原理证明，作为功能性萜烯合成酶模拟物的第一个例子，并探索简单包封作为催化的酶促策略。模拟酶的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。提出了一种四面体配位笼配合物来模拟一类称为单萜合成酶的酶的功能。无环萜烯前体在配合物的带负电腔内的结合将催化它们以仿生的方式阳离子环化成单萜的对甲烷家族。

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.