Does the radical GPRI strongly depend on the population scheme? A comparative study to predict radical attack on unsaturated molecules with the radical general-purpose reactivity indicator.

The reactivity of 22 unsaturated molecules undergoing attack by a methyl radical (⋅CH3) have been elucidated using the condensed radical general-purpose reactivity indicator (condensed radical GPRI) appropriate for relatively nucleophilic or electrophilic molecules. Using the appropriate radical GPRI equation for electrophilic attack or nucleophilic radical attack, seven different population schemes were used to assign the most reactive atoms in each of the 22 molecules. The results show that the condensed radical GPRI is sensitive to the population scheme chosen, but less sensitive than the radical Fukui function. Therefore, the reliability of these methods depends on the population scheme. Our investigation indicates that the condensed radical GPRI is most accurate in predicting the dominant products of the methyl radical addition reactions on a variety of unsaturated molecules when the Hirshfeld, Merz-Singh-Kollman, or Voronoi deformation density population schemes are used. Furthermore, for all populations schemes in the majority of instances where the radical Fukui function failed the radical GPRI was able to identify the most reactive atom under certain reactivity conditions.

Using the general-purpose reactivity indicator: challenging examples.

We elucidate the regioselectivity of nucleophilic attack on substituted benzenesulfonates, quinolines, and pyridines using a general-purpose reactivity indicator (GPRI) for electrophiles. We observe that the GPRI is most accurate when the incoming nucleophile resembles a point charge. We further observe that the GPRI often chooses reactive "dead ends" as the most reactive sites as well as sterically hindered reactive sites. This means that care must be taken to remove sites that are inherently unreactive. Generally, among sites where reactions actually occur, the GPRI identifies the sites in the molecule that lead to the kinetically favored product(s). Furthermore, the GPRI can discern which sites react with hard reagents and which sites react with soft reagents. Because it is currently impossible to use the mathematical framework of conceptual DFT to identify sterically inaccessible sites and reactive dead ends, the GPRI is primarily useful as an interpretative, not a predictive, tool.