TY - JOUR
T1 - Exploring solvent effects upon the menshutkin reaction using a polarizable force field
AU - Acevedo, Orlando
AU - Jorgensen, William L.
N1 - Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2010/7/1
Y1 - 2010/7/1
N2 - The energetics of the Menshutkin reaction between triethylamine and ethyl iodide have been computed using B3LYP and MP2 with the LANL2DZ, LANL2DZd, SVP, MIDI!, 6-311G(d,p), and aug-cc-PVTZ basis sets. Small- and large-core energy-consistent relativistic pseudopotentials were employed. Solvent effect corrections were computed from QM/MM Monte Carlo simulations utilizing free-energy perturbation theory, PDDG/PM3, and both a nonpolarizable OPLS and polarizable OPLS-AAP force field. The B3LYP/MIDI! theory level provide the best ΔG‡ values with a mean absolute error (MAE) of 4.9 kcal/mol from experiment in cyclohexane, CCl4, THF, DMSO, acetonitrile, water, and methanol. However, the relative rates in cyclohexane, and to a certain extent CCl4, were determined to be greatly underestimated when using the nonpolarizable OPLS force field. An overall reduction in the MAE to 3.1 kcal/mol using B3LYP/MIDI!/OPLS-AAP demonstrated the need for a fully polarizable force field when computing solvent effects for highly dipolar transition structures in low-dielectric media. The MAEs obtained with PDDG/PM3/OPLS and OPLS-AAP of 5.3 and 3.8 kcal/mol, respectively, provided comparable results to B3LYP at a fraction of the computational resources. The large rate accelerations observed in the reaction were correlated to an increased stabilization of the emerging charge separation at the transition state via favorable solute-solvent interactions.
AB - The energetics of the Menshutkin reaction between triethylamine and ethyl iodide have been computed using B3LYP and MP2 with the LANL2DZ, LANL2DZd, SVP, MIDI!, 6-311G(d,p), and aug-cc-PVTZ basis sets. Small- and large-core energy-consistent relativistic pseudopotentials were employed. Solvent effect corrections were computed from QM/MM Monte Carlo simulations utilizing free-energy perturbation theory, PDDG/PM3, and both a nonpolarizable OPLS and polarizable OPLS-AAP force field. The B3LYP/MIDI! theory level provide the best ΔG‡ values with a mean absolute error (MAE) of 4.9 kcal/mol from experiment in cyclohexane, CCl4, THF, DMSO, acetonitrile, water, and methanol. However, the relative rates in cyclohexane, and to a certain extent CCl4, were determined to be greatly underestimated when using the nonpolarizable OPLS force field. An overall reduction in the MAE to 3.1 kcal/mol using B3LYP/MIDI!/OPLS-AAP demonstrated the need for a fully polarizable force field when computing solvent effects for highly dipolar transition structures in low-dielectric media. The MAEs obtained with PDDG/PM3/OPLS and OPLS-AAP of 5.3 and 3.8 kcal/mol, respectively, provided comparable results to B3LYP at a fraction of the computational resources. The large rate accelerations observed in the reaction were correlated to an increased stabilization of the emerging charge separation at the transition state via favorable solute-solvent interactions.
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U2 - 10.1021/jp100765v
DO - 10.1021/jp100765v
M3 - Article
C2 - 20527873
AN - SCOPUS:77953963602
VL - 114
SP - 8425
EP - 8430
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
SN - 1520-6106
IS - 25
ER -