Theoretical thermodynamics for large molecules: walking the thin line between accuracy and computational cost

Area of Science:

• Quantum chemistry
• Computational physics
• Molecular modeling

Background:

• Accurate prediction of molecular thermodynamic properties is crucial across physics, chemistry, and biology.
• Developing computational methods applicable to larger molecules remains a significant challenge.

Purpose of the Study:

• To present advancements in quantum chemical electronic structure methods for large molecules.
• To achieve target accuracies of 0.5-1 kcal mol(-1) for reactions and 0.1 kcal mol(-1) for conformational energies.
• To maintain computational expense comparable to standard methods.

Main Methods:

• Incorporation of physically motivated corrections into first-principles methods.
• Use of density-fitting (RI) integral approximations for efficiency.
• Application of modified second-order perturbation theory for electron correlation.
• Development and application of spin-component-scaled Møller-Plesset perturbation theory (SCS-MP2) and double-hybrid density functionals (DHDF).
• Inclusion of empirical dispersion corrections (DFT-D).

Main Results:

• Routine computations on systems with ~100 non-hydrogen atoms are feasible on modern PCs.
• SCS-MP2 and DHDF methods, combined with large basis sets, achieve accuracy competitive with coupled-cluster methods.
• The B2PLYP-D functional demonstrates a low mean absolute deviation (1.7 kcal mol(-1)) for the G3/99 heat of formation benchmark.
• SCS-MP2 effectively avoids self-interaction errors prevalent in density functional theory (DFT).

Conclusions:

• The developed methods provide accurate and computationally feasible approaches for studying the thermodynamics of large molecules.
• B2PLYP-D is recommended for heat of formation and complex electronic systems (e.g., transition metals).
• SCS-MP2 is the preferred method for closed-shell main-group molecules and relative energies, avoiding self-interaction errors.