Describing the Disulfide Bond: From the Density Functional Theory and Back through the "Lego Brick" Approach.

Area of Science:

• Computational chemistry
• Quantum chemistry
• Molecular modeling

Background:

• Disulfide bonds (RSSR) are crucial in various chemical and biological systems.
• Accurate determination of molecular structures, especially the S-S bond, is essential for understanding their properties.
• Existing computational methods may not offer an optimal balance between accuracy and cost for flexible disulfide molecules.

Purpose of the Study:

• To investigate and compare different computational approaches for deriving accurate equilibrium structures of disulfide species.
• To benchmark cost-effective density functional theory (DFT) methodologies for analyzing the S-S bond and related structural parameters.
• To identify reliable and affordable computational strategies for studying a range of disulfide compounds from H2S2 to diphenyl disulfide.

Main Methods:

• Exploration of various computational strategies, including a semiexperimental approach with a reduced-dimensionality VPT2 model.
• Application of the "Lego brick" approach for geometrical determination of flexible disulfide systems.
• Benchmarking of several DFT functionals (e.g., PBE0, M06-2X, DSD-PBEP86) with dispersion corrections (e.g., -D3BJ, -D3).

Main Results:

• The semiexperimental approach combined with VPT2 did not yield satisfactory results for the investigated disulfide species.
• The "Lego brick" approach demonstrated high effectiveness in determining accurate equilibrium structures, even for flexible molecules.
• PBE0(-D3BJ), M06-2X(-D3), and DSD-PBEP86-D3BJ were identified as the best-performing DFT functionals for analyzing S-S bond parameters.

Conclusions:

• The "Lego brick" approach is a highly effective and cost-efficient strategy for accurate structural determination of disulfide compounds.
• Specific DFT functionals, namely PBE0(-D3BJ), M06-2X(-D3), and DSD-PBEP86-D3BJ, provide reliable benchmarks for studying the S-S bond in these molecules.
• This work offers valuable insights for selecting appropriate computational tools in disulfide chemistry research.