Towards Universal Substituent Constants: Relating QTAIM Functional Group Descriptors to Substituent Effect Proxies

Substituents modulate reactions, but are commonly described using proxies to their true properties. Substituent descriptors from the Quantum Theory of Atoms in Molecules are related here to these proxies, which have historically had chemically intuitable effects. Due to the large number of descriptors, multivariate analysis is used to intuit their meaning. Multiple linear regression, Principal Components, and Partial Least Squares Regression analyses highlight that these substituent descriptors contain similar information to the proxies, while being truly substituent properties. Sources of error limiting quantitative reproduction of the proxies data include transferability, experimental accuracy, and solvation issues.