Enzyme-Like Catalysis of the Nazarov Cyclization by Supramolecular Encapsulation

Hastings, Courtney; Pluth, Michael; Bergman, Robert; Raymond, Kenneth

doi:10.1021/ja102633e

Title: Enzyme-Like Catalysis of the Nazarov Cyclization by Supramolecular Encapsulation

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Abstract

A primary goal in the design and synthesis of molecular hosts has been the selective recognition and binding of a variety of guests using non-covalent interactions. Supramolecular catalysis, which is the application of such hosts towards catalysis, has much in common with many enzymatic reactions, chiefly the use of both spatially appropriate binding pockets and precisely oriented functional groups to recognize and activate specific substrate molecules. Although there are now many examples which demonstrate how selective encapsulation in a host cavity can enhance the reactivity of a bound guest, all have failed to reach the degree of increased reactivity typical of enzymes. We now report the catalysis of the Nazarov cyclization by a self-assembled coordination cage, a carbon-carbon bond-forming reaction which proceeds under mild, aqueous conditions. The acceleration in this system is over a million-fold, and represents the first example of supramolecular catalysis that achieves the level of rate enhancement comparable to that observed in several enzymes. We explain the unprecedented degree of rate increase as due to the combination of (a) preorganization of the encapsulated substrate molecule, (b) stabilization of the transition state of the cyclization by constrictive binding, and (c) increase in the basicity of the complexed alcoholmore » functionality.« less

Authors:: Hastings, Courtney; Pluth, Michael; Bergman, Robert; Raymond, Kenneth

Publication Date:: Mon Mar 29 00:00:00 EDT 2010

Research Org.:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Org.:: Chemical Sciences Division

OSTI Identifier:: 1013063

Report Number(s):: LBNL-3969E
Journal ID: ISSN 0002--7863; TRN: US201110%%427

DOE Contract Number:: DE-AC02-05CH11231

Resource Type:: Journal Article

Journal Name:: Journal of the American Chemical Society

Additional Journal Information:: Journal Volume: 132; Journal Issue: 20; Journal ID: ISSN 0002--7863

Country of Publication:: United States

Language:: English

Subject:: 37; ACCELERATION; ALCOHOLS; CATALYSIS; CYCLIZATION; DESIGN; ENCAPSULATION; ENZYMES; FUNCTIONALS; STABILIZATION; SUBSTRATES; SYNTHESIS

Citation Formats


                    Hastings, Courtney, Pluth, Michael, Bergman, Robert, and Raymond, Kenneth. Enzyme-Like Catalysis of the Nazarov Cyclization by Supramolecular Encapsulation.  United States: N. p., 2010. 
        Web.  doi:10.1021/ja102633e.

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                    Hastings, Courtney, Pluth, Michael, Bergman, Robert, & Raymond, Kenneth. Enzyme-Like Catalysis of the Nazarov Cyclization by Supramolecular Encapsulation.  United States.  https://doi.org/10.1021/ja102633e

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                    Hastings, Courtney, Pluth, Michael, Bergman, Robert, and Raymond, Kenneth. 2010.  
        "Enzyme-Like Catalysis of the Nazarov Cyclization by Supramolecular Encapsulation".  United States.  https://doi.org/10.1021/ja102633e.  https://www.osti.gov/servlets/purl/1013063.

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@article{osti_1013063,

  title        = {Enzyme-Like Catalysis of the Nazarov Cyclization by Supramolecular Encapsulation},

  author       = {Hastings, Courtney and Pluth, Michael and Bergman, Robert and Raymond, Kenneth},

  abstractNote = {A primary goal in the design and synthesis of molecular hosts has been the selective recognition and binding of a variety of guests using non-covalent interactions. Supramolecular catalysis, which is the application of such hosts towards catalysis, has much in common with many enzymatic reactions, chiefly the use of both spatially appropriate binding pockets and precisely oriented functional groups to recognize and activate specific substrate molecules. Although there are now many examples which demonstrate how selective encapsulation in a host cavity can enhance the reactivity of a bound guest, all have failed to reach the degree of increased reactivity typical of enzymes. We now report the catalysis of the Nazarov cyclization by a self-assembled coordination cage, a carbon-carbon bond-forming reaction which proceeds under mild, aqueous conditions. The acceleration in this system is over a million-fold, and represents the first example of supramolecular catalysis that achieves the level of rate enhancement comparable to that observed in several enzymes. We explain the unprecedented degree of rate increase as due to the combination of (a) preorganization of the encapsulated substrate molecule, (b) stabilization of the transition state of the cyclization by constrictive binding, and (c) increase in the basicity of the complexed alcohol functionality.},

  doi          = {10.1021/ja102633e},

  url          = {https://www.osti.gov/biblio/1013063},
  journal      = {Journal of the American Chemical Society},

  issn         = {0002--7863},

  number       = 20,

  volume       = 132,

  place        = {United States},

  year         = {Mon Mar 29 00:00:00 EDT 2010},

  month        = {Mon Mar 29 00:00:00 EDT 2010}

}

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