Small Molecule Thermochemistry: A Tool for Empirical Force Field Development

Spectroscopic
analysis of compounds is typically combined with
density functional theory, for instance, for assigning vibrational
frequencies, limiting application to relatively small compounds. Accurate
classical force fields could, in principle, complement these quantum-chemical
tools. A relatively simple way to validate vibrational frequencies
is by computing thermochemical properties. We present such a validation
for over 1800 small molecules using the harmonic approximation. Two
popular empirical force fields (GAFF and CGenFF) are compared to experimental
data and results from Gaussian-4 quantum-chemical calculations. Frequency
scaling factors of 1.035 (CGenFF) and 1.018 (GAFF) are derived from
the zero-point energies. The force field calculations have larger
deviation from experiment than the G4 method for standard entropy,
but for heat capacity the results are comparable. For internal thermal
energy and zero-point energy the deviations from G4 are relatively
small. The work suggests that with some tuning force fields could
indeed complement DFT in spectroscopical applications.