Small Molecule Thermochemistry: A Tool for Empirical Force Field Development.

Area of Science:

• Computational chemistry
• Molecular modeling
• Spectroscopy

Background:

• Density functional theory (DFT) is commonly used for spectroscopic analysis, but its application is limited to small molecules.
• Accurate classical force fields offer a potential alternative for complementing quantum-chemical methods in spectroscopy.
• Thermochemical properties provide a viable route for validating vibrational frequencies computed by force fields.

Purpose of the Study:

• To validate the accuracy of empirical force fields (GAFF and CGenFF) for computing thermochemical properties.
• To assess the potential of force fields to complement DFT in spectroscopic applications.
• To compare force field performance against experimental data and high-level quantum-chemical calculations.

Main Methods:

• Validation of vibrational frequencies using computed thermochemical properties for over 1800 small molecules.
• Application of the harmonic approximation for calculations.
• Comparison of General Amber Force Field (GAFF) and CHARMM General Force Field (CGenFF) against experimental data and Gaussian-4 (G4) calculations.

Main Results:

• Frequency scaling factors derived from zero-point energies: 1.035 for CGenFF and 1.018 for GAFF.
• Force field calculations showed greater deviation from experimental standard entropy compared to the G4 method.
• Force field and G4 methods yielded comparable results for heat capacity.
• Deviations of force fields from G4 for internal thermal energy and zero-point energy were relatively small.

Conclusions:

• Empirical force fields, with appropriate tuning, can serve as valuable complements to DFT for spectroscopic analyses.
• The study demonstrates the utility of thermochemical property calculations for validating force fields in vibrational spectroscopy.
• Force fields show promise for extending spectroscopic analysis to larger molecular systems than currently feasible with DFT.