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E/Z Energetics for Molecular Modeling and Design.

ABSTRACT: Thermochemical data have been obtained from G3B3 quantum mechanical calculations for 18 prototypical organic molecules, which exhibit E/Z conformational equilibria. The results are fundamentally important for molecular design including evaluation of structures from protein-ligand docking. For the 18 E/Z pairs, relative energies, enthalpies, free energies, and dipole moments are reported; the E - Z free-energy differences at 298 K range from +8.2 kcal/mol for 1,3-dimethyl carbamate to -6.4 kcal/mol for acetone oxime. A combination of steric and electronic effects can rationalize the variations. Free energies of hydration were also estimated using the GB/SA continuum solvent model. These results indicate that differential hydration is unlikely to qualitatively change the preferred direction of the E/Z equilibria, though further study with free-energy methods using explicit solvent is desirable.

SUBMITTER: Terhorst JP

PROVIDER: S-EPMC2943632 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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E/Z Energetics for Molecular Modeling and Design.

Terhorst John P JP Jorgensen William L WL

Journal of chemical theory and computation 20100901 9

Thermochemical data have been obtained from G3B3 quantum mechanical calculations for 18 prototypical organic molecules, which exhibit E/Z conformational equilibria. The results are fundamentally important for molecular design including evaluation of structures from protein-ligand docking. For the 18 E/Z pairs, relative energies, enthalpies, free energies, and dipole moments are reported; the E - Z free-energy differences at 298 K range from +8.2 kcal/mol for 1,3-dimethyl carbamate to -6.4 kcal/m ...[more]

PMID: 20871784

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