Range-Separated DFT Functionals are Necessary to Model Thio-Michael Additions

Area of Science:

• Computational Chemistry
• Organic Chemistry
• Biochemistry

Background:

• The Michael-type addition is a key reaction mechanism involving thiols and alkenes.
• Previous computational models failed to identify carbanion intermediates, suggesting alternative reaction pathways.
• This discrepancy arises from errors in common density functional theory (DFT) functionals.

Purpose of the Study:

• To investigate the accuracy of DFT functionals in modeling Michael-type additions.
• To identify computational methods that correctly predict carbanion intermediate stability.
• To enable accurate modeling of biochemical reactions involving thiol-ene additions.

Main Methods:

• Evaluation of various pure and hybrid DFT functionals (e.g., PBE, B3LYP).
• Utilizing range-separated DFT functionals, specifically ωB97X-D.
• Comparison of DFT results with high-level coupled cluster calculations (CCSD(T)).

Main Results:

• Popular DFT functionals (PBE, B3LYP) erroneously predict no carbanion intermediate due to delocalization error.
• These functionals favor spurious noncovalent charge-transfer complexes.
• Range-separated DFT functionals, particularly ωB97X-D, accurately predict stable carbanion structures and energies.
• ωB97X-D results show excellent agreement with CCSD(T) data.

Conclusions:

• Range-separated DFT functionals resolve the inaccuracies of standard DFT methods for Michael-type additions.
• Accurate computational modeling of thio-carbanion intermediates is now feasible.
• This advancement facilitates the study of biochemical processes like drug modification of cysteine residues.