Development and Validation of Atomic Group Descriptors for Substituent Effects

ABSTRACT Substituent constants are often described with experimental proxies based on a simplified substituent effect model. While good insights have been derived from such proxies, the true properties of the substituent, through which a more thorough understanding of the substituent effect might be assessed, are not often investigated. Here, we have developed an atomic graph descriptor model for substituent properties using the Quantum Theory of Atoms in Molecules, comprising atomic, bond critical point, and charge concentration properties. These descriptors are shown to contain similar information to some traditionally used field and resonance parameters. The use of such descriptors for studying the substituent effect should provide greater insights into the true origin of the effect that substituents have on molecular systems.