Revealing Structure–Function Relationships Involving Substituent Position for Isoquinoline Photobases

Abstract

ABSTRACT Photobases are molecules that become much stronger bases upon photoexcitation. Previous experimental work has carefully characterized structure–function relationships for 5‐substituted quinolines, demonstrating that the thermodynamic driving force for excited‐state protonation increases as the substituent becomes more electron‐donating. Subsequent computational work examined possible descriptors for photobasicity in this family. However, a detailed analysis of how photobasicity strength is affected by changes in substituent position is lacking in the literature. In this work, we fill this gap by experimentally demonstrating that the ground‐ and excited‐state basicity of bromoisoquinolines is significantly modulated by the position of the bromine atom. Complementary computational work applies descriptors based on intramolecular charge‐transfer, excited‐state antiaromaticity relief, and energy decomposition analysis to these photobases. Overall, this study provides new insights into structure–function relationships involving N ‐heterocycle photobases.