Revisiting the Maximum Hardness Principle: A Quantitative Analysis on Reaction Datasets

Area of Science:

• Theoretical Chemistry
• Chemical Reactivity Theory
• Conceptual Density Functional Theory (CDFT)

Background:

• Chemical hardness is a key concept in understanding chemical reactivity.
• The maximum hardness principle (MHP) suggests reactions proceed towards states of maximum hardness.
• Previous studies have raised questions about the universal applicability of MHP.

Purpose of the Study:

• To quantitatively assess the applicability of the MHP.
• To investigate the influence of different computational approximations on MHP validity.
• To analyze MHP's reliability across diverse reaction types.

Main Methods:

• Utilized two reaction datasets: 5269 dipolar cycloadditions and 449 BH9 reactions.
• Employed Kohn-Sham orbital based frontier molecular orbital (FMO) and finite difference approximation (FDA) for hardness calculations.
• Examined the impact of various definitions for average hardness in bimolecular reactions.

Main Results:

• Hardness values are sensitive to the level of theory, definitions, and approximations used.
• Approximately 80% of the 5269 cycloaddition reactions adhere to the MHP.
• MHP is better supported for unimolecular reactions in the BH9 dataset; its validity in bimolecular reactions depends heavily on the hardness definition.

Conclusions:

• The validity of MHP is influenced by computational methodology and reaction characteristics.
• Reactions with significantly different reactant hardness values are less likely to obey MHP.
• As a qualitative principle, MHP's universality is not expected, emphasizing the need for careful interpretation.