Stepping-Stone CBH: Benchmark and Application of a Multilayered Isodesmic-Based Correction Scheme

Area of Science:

• Computational Chemistry
• Quantum Chemistry
• Theoretical Chemistry

Background:

• Connectivity-based hierarchy (CBH) methods offer accurate isodesmic-based corrections for molecular properties.
• Traditional CBH approaches can be computationally expensive, limiting their application to larger systems.
• Accurate calculation of enthalpies for organic molecules is crucial in various chemical disciplines.

Purpose of the Study:

• To develop a generalized, multilayered fragmentation platform for CBH schemes.
• To introduce the stepping-stone CBH (SSCBH) approach for cost reduction while maintaining high accuracy.
• To enable broader applications of CBH methods in organic and biomolecular systems.

Main Methods:

• Generalization of CBH schemes to a multilayered fragmentation platform.
• Development and implementation of the stepping-stone CBH (SSCBH) methodology.
• Benchmarking SSCBH on a diverse set of 959 medium-sized organic molecules using PBEh-D3 functional.

Main Results:

• SSCBH achieved an average error of 0.76 kcal/mol for enthalpies on the full test set compared to CCSD(T) quality.
• A subset of acyclic molecules showed an even lower average error of 0.44 kcal/mol.
• SSCBH rivals traditional CBH-3 accuracy at a significantly reduced computational cost, enabling MP2-level corrections instead of G4.

Conclusions:

• The novel SSCBH approach offers a cost-effective and accurate alternative for calculating molecular enthalpies.
• This method significantly lowers the computational expense associated with CBH corrections.
• SSCBH is poised to expand the applicability of CBH methods to larger and more complex organic and biomolecular systems.