Cofactor-Mediated Nucleophilic Substitution Catalyzed by a Self-Assembled Holoenzyme Mimic
Cofactor-Mediated Nucleophilic Substitution Catalyzed by a Self-Assembled Holoenzyme Mimic
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DOI：
10.1021/acs.joc.9b01880
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发表时间：
2019-09-20
影响因子：
3.6
通讯作者：
Hooley, Richard J.
中科院分区：
文献类型：
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作者：
Ngai, Courtney;Bogie, Paul M.;Hooley, Richard J.
自组装的Fe4L6笼子能够在其空腔中共包裹多个含有客体的羧酸，这些酸可以作为笼子催化的亲核取代的辅助因子。取代反应的动力学取决于每个组分的大小、形状和结合亲和力，客体大小的微小结构变化可以对反应产生很大影响。宿主是相当混杂的，能够用微摩尔结合亲和力结合多个客体，同时保持影响周转和催化的能力。底物结合模式变化很大，从简单的1：1络合物到1：2络合物，根据客体的不同，可以表现出负的或正的协同性。解离取代反应的分子量随亲电离基团、酸性辅因子和亲核试剂大小的不同而不同：底物性质的微小变化可以对反应动力学产生很大影响，所有这些都由笼子内部的选择性分子识别控制。
A self-assembled Fe4L6 cage is capable of co-encapsulating multiple carboxylic acid containing guests in its cavity, and these acids can act as cofactors for cage-catalyzed nucleophilic substitutions. The kinetics of the substitution reaction depend on the size, shape, and binding affinity of each of the components, and small structural changes in guest size can have large effects on the reaction. The host is quite promiscuous and is capable of binding multiple guests with micromolar binding affinities while retaining the ability to effect turnover and catalysis. Substrate binding modes vary widely, from simple 1:1 complexes to 1:2 complexes that can show either negative or positive cooperativity, depending on the guest. The molecularity of the dissociative substitution reaction varies, depending on the electrophile leaving group, acid cofactor, and nucleophile size: small changes in the nature of substrate can have large effects on reaction kinetics, all controlled by selective molecular recognition in the cage interior.