Using the general-purpose reactivity indicator: challenging examples

• Published in: Journal of molecular modeling Vol. 22; no. 3; p. 57
• Main Authors: Anderson, James S. M., Melin, Junia, Ayers, Paul W.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2016
• Subjects: Algorithms; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Models, Chemical; Models, Molecular; Models, Theoretical; Molecular Medicine; Original Paper; Theoretical and Computational Chemistry; General purpose reactivity indicator; Fukui function; Conceptual density functional theory; Reactivity transition table; Electrostatic potential
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-016-2910-7

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.