Journal of the American Chemical Society
of a case study is that it identifies problems for consideration in
Page 14 of 15
the experimental complications (see text) led to an accidental corre-
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other cases, and the results here suggest a variety of issues that
should be carefully considered in the execution and interpretation
of computational mechanistic studies.
spondence of predicted and experimental entropies.
(13) (a) Xu, J. J. Mol. Struct. THEOCHEM 2006, 767, 61-66. (b) This
B3LYP/6-311+G*/PCM study of a phosphine-catalyzed model reaction
concluded that a 1,3-proton transfer in 2 was rate limiting. The computa-
tional results were described as “in good agreement with the previous
experimental results” though the calculated free-energy barrier of 63.2
kcal/mol would lead to rates that are roughly 1030 lower than experimen-
tally observed rates.
(14) (a) Fan, J. –F.; Yang, C. –H.; He, L. –J. Int. J. Quantum Chem.
2009, 74, 3031. (b) This B3LYP/6-311++G**/CPCM study of a trime-
thylamine / acrolein / formaldehyde / methanol model reaction supports
the Aggarwal / Harvey proton-shuttle mechanism. The calculated ΔG‡ of
50 kcal/mol would lead to rates that are 20 orders of magnitude lower
than experimentally observed rates.
(15) (a) Li, J.; Jiang, W. –Y. J. Theor. Comput. Chem. 2010, 9, 65-75.
(b) This B3LYP/6-31+G**/CPCM study of a trimethylamine / acrolein
/ formaldehyde / water model reaction supports the proton-shuttle
mechanism, and concluded that “the calculated overall reaction barrier is
in agreement with experimental observations.” However, the calculated
“free energy” barriers did not include any allowance for solute entropy.
This is a common error in the literature. (See Ho, J.; Klamt, A.; Coote,
M. L. J. Phys. Chem. A 2010, 114, 13442-13444 and Ribeiro, R. F.;
Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. A 2011, 115,
14556-14562 for discussions. For a second example, see ref 17a.). The
typical error is 12 kcal/mol for bimolecular equilibria and 24 kcal/mol for
trimolecular equilibria. If the full calculated solute entropy were included,
the barrier would be >50 kcal/mol.
ASSOCIATED CONTENT
Supporting Information.
Experimental and computational procedures, geometries and ener-
gies of calculated structures, data analyses. This material is available
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AUTHOR INFORMATION
Corresponding Author
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank the NIH (Grant GM-45617) for financial support. We
thank J. Peter Guthrie for helpful discussions.
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