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Title: Three Hydrogen Bond Donor Catalysts: Oxyanion Hole Mimics and Transition State Analogues

Abstract

Enzymes and their mimics use hydrogen bonds to catalyze chemical transformations. Small molecule transition state analogs of oxyanion holes are characterized by gas phase IR and photoelectron spectroscopy and their binding constants in acetonitrile. As a result, a new class of hydrogen bond catalysts is proposed (OH donors that can contribute three hydrogen bonds to a single functional group) and demonstrated in a Friedel-Crafts reaction.

Authors:
; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1059186
Report Number(s):
PNNL-SA-88858
44678; 42590; KC0301020
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of the American Chemical Society, 134(45):18534-18537
Country of Publication:
United States
Language:
English
Subject:
Environmental Molecular Sciences Laboratory

Citation Formats

Beletskiy, Evgeny V., Schmidt, Jacob C., Wang, Xue B., and Kass, Steven R. Three Hydrogen Bond Donor Catalysts: Oxyanion Hole Mimics and Transition State Analogues. United States: N. p., 2012. Web. doi:10.1021/ja3085862.
Beletskiy, Evgeny V., Schmidt, Jacob C., Wang, Xue B., & Kass, Steven R. Three Hydrogen Bond Donor Catalysts: Oxyanion Hole Mimics and Transition State Analogues. United States. doi:10.1021/ja3085862.
Beletskiy, Evgeny V., Schmidt, Jacob C., Wang, Xue B., and Kass, Steven R. 2012. "Three Hydrogen Bond Donor Catalysts: Oxyanion Hole Mimics and Transition State Analogues". United States. doi:10.1021/ja3085862.
@article{osti_1059186,
title = {Three Hydrogen Bond Donor Catalysts: Oxyanion Hole Mimics and Transition State Analogues},
author = {Beletskiy, Evgeny V. and Schmidt, Jacob C. and Wang, Xue B. and Kass, Steven R.},
abstractNote = {Enzymes and their mimics use hydrogen bonds to catalyze chemical transformations. Small molecule transition state analogs of oxyanion holes are characterized by gas phase IR and photoelectron spectroscopy and their binding constants in acetonitrile. As a result, a new class of hydrogen bond catalysts is proposed (OH donors that can contribute three hydrogen bonds to a single functional group) and demonstrated in a Friedel-Crafts reaction.},
doi = {10.1021/ja3085862},
journal = {Journal of the American Chemical Society, 134(45):18534-18537},
number = ,
volume = ,
place = {United States},
year = 2012,
month =
}
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  • Enzymes are classically proposed to accelerate reactions by binding substrates within active-site environments that are structurally preorganized to optimize binding interactions with reaction transition states rather than ground states. This is a remarkably formidable task considering the limited 0.1--1 {angstrom} scale of most substrate rearrangements. The flexibility of active-site functional groups along the coordinate of substrate rearrangement, the distance scale on which enzymes can distinguish structural rearrangement, and the energetic significance of discrimination on that scale remain open questions that are fundamental to a basic physical understanding of enzyme active sites and catalysis. We bring together 1.2--1.5 {angstrom} resolution X-raymore » crystallography, {sup 1}H and {sup 19}F NMR spectroscopy, quantum mechanical calculations, and transition-state analogue binding measurements to test the distance scale on which noncovalent forces can constrain the structural relaxation or translation of side chains and ligands along a specific coordinate and the energetic consequences of such geometric constraints within the active site of bacterial ketosteroid isomerase (KSI). Our results strongly suggest that packing and binding interactions within the KSI active site can constrain local side-chain reorientation and prevent hydrogen bond shortening by 0.1 {angstrom} or less. Further, this constraint has substantial energetic effects on ligand binding and stabilization of negative charge within the oxyanion hole. These results provide evidence that subtle geometric effects, indistinguishable in most X-ray crystallographic structures, can have significant energetic consequences and highlight the importance of using synergistic experimental approaches to dissect enzyme function.« less
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