Multidimensional exploration of valley-ridge inflection points on potential-energy surfaces

April N. Sheppard, Orlando Acevedo

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


The ene reaction between singlet oxygen ( 1O 2) and simple alkenes has been reported as the first experimentally supported example of a potential-energy surface (PES) featuring a valley-ridge inflection that contributes to the selectivity of product formation (J. Am. Chem. Soc. 2003, 125, 1319-1328). That PES, based on gas-phase ab initio calculations and experimental kinetic isotope effects, has shaped the current 1O 2 ene mechanism by advocating a concerted "two-step no-intermediate" mechanism. Our current investigation of the ene reaction between 1O 2 and tetramethylethylene in water, DMSO, and cyclohexane using novel 3-dimensional potentials of mean force (3-D PMF) calculations coupled to QM/MM simulations predicts an alternative free-energy surface that supports a traditional stepwise mechanism interpretation featuring a symmetric charge-separated perepoxide intermediate. Solvent polarity dictates the stability of the intermediate and controls the activation barrier for ene product formation. Transformation of the higher order condensed-phase 3-D PMF potential-energy surface, computed following three simultaneous reaction coordinates, into a downgraded 2-D surface results in the "two-step no-intermediate" mechanism. CCSD(T) and MP4(SDQ) free-energy maps in DMSO, constructed from a 3-D grid of B3LYP geometries using the CPCM solvent model, reproduce the QM/MM results and confirm that when solvent is taken into account the gas-phase bifurcation reaction pathway converts into a stepwise mechanism. This manuscript provides new insight into the biologically and synthetically important 1O 2 ene reaction and highlights a new multidimensional approach for constructing potential-energy surfaces.

Original languageEnglish (US)
Pages (from-to)2530-2540
Number of pages11
JournalJournal of the American Chemical Society
Issue number7
StatePublished - Feb 25 2009
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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