posted on 2020-03-25, 20:10authored byRupesh Agarwal, Micholas Dean Smith, Jeremy C. Smith
Deuteration is a
common chemical modification used in conjunction
with experiments such as neutron scattering, NMR, and Fourier-transform
infrared for the study of molecular systems. Under the Born–Oppenheimer
(BO) approximation, while the underlying potential energy surface
remains unchanged by isotopic substitutions, isotopic substitution
still alters intramolecular vibrations, which in turn may alter intermolecular
interactions. Molecular mechanics (MM) force fields used in classical
molecular dynamics simulations are assumed to represent local approximations
of the BO potential energy surfaces, and hence, MD simulations using
simple isotopic mass substitutions should capture BO-compatible isotope
effects. However, standard MM force-field parameterizations do not
directly fit to the local harmonic quantum mechanical (QM) Hessian
that describes the BO surface, but rather to QM normal-modes and/or
mass-dependent internal-coordinate derived distortion energies. Here,
using tetrahydrofuran (THF)–water mixtures as our model system,
we show that not only does a simple mass-substitution approach fail
to capture an experimentally characterized deuteration effect (the
loss of the closed-loop miscibility gap associated with the complete
deuteration of THF) but also it is necessary to generate new MM force-field
parameters that correctly describe isotopic dependent vibrations to
capture the experimental deuteration effect. We show that the origin
of this failure is a result of using mass-dependent features to fit
the THF MM force field, which unintentionally biases the bonded terms
of the force field to represent only the isotopologue used during
the original force-field parameterization. In addition, we make use
of our isotopologue-corrected force field for D8THF to
examine the molecular origins of the isotope-dependent loss of the
THF–water miscibility gap.