Stereoelectronic requirements for optimal hydrogen-bond-catalyzed enolization

Chemistry. 2011 Mar 1;17(10):2859-66. doi: 10.1002/chem.201002943. Epub 2011 Feb 9.

Abstract

Protein crystallographic analysis of the active sites of enolizing enzymes and structural analysis of hydrogen-bonded carbonyl compounds in small molecule crystal structures, complemented by quantum chemical calculations on related model enolization reactions, suggest a new stereoelectronic model that accounts for the observed out-of-plane orientation of hydrogen-bond donors (HBDs) in the oxyanion holes of enolizing enzymes. The computational results reveal that the lone-pair directionality of HBDs characteristic for hydrogen-bonded carbonyls is reduced upon enolization, and the enolate displays almost no directional preference for hydrogen bonding. Positioning the HBDs perpendicular to the carbonyl plane induces strain in the catalyst-substrate complex, which is released upon enolization, resulting in more favorable kinetics and thermodynamics than the in-plane arrangement of HBDs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Carbon-Carbon Double Bond Isomerases / chemistry
  • Carbon-Carbon Double Bond Isomerases / metabolism*
  • Catalysis
  • Humans
  • Hydrogen Bonding
  • Ketones / chemistry*
  • Mitochondria / enzymology
  • Models, Molecular*
  • Stereoisomerism
  • Thermodynamics

Substances

  • Ketones
  • Carbon-Carbon Double Bond Isomerases