Visible Light Activatable Photocages: Structure–Activity Relationship Study on 8‐Substituted 7‐Hydroxyquinoline‐2‐ylmethyl Photoremovable Protecting Groups

Abstract

Among photoremovable protecting groups (PPGs), the 7‐hydroxyquinoline‐2‐ylmethyl‐based cage stands out for versatility, potential biological applications, and tunability of photophysical properties through modification of the substitution pattern at the quinoline nucleus. The introduction of electron‐withdrawing atoms/groups (EWGs) at quinoline C(8) profoundly affects its photochemical performance. Interested in caging tertiary amines because they are prevalent in a variety of biologically active compounds and photouncaging them with biocompatible visible light, we chose N ‐benzylpyrrolidine as an aliphatic tertiary amine model and synthesized a series of N ‐benzylpyrrolidines N ‐caged with 7‐hydroxyquinoline‐2‐ylmethyl 8‐substituted with different EWGs (halogen, cyano, methylsulfonyl, trifluoromethyl, and carboxyl). Photophysical characterization of the new constructs revealed that the 8‐halo‐substituted derivatives, unlike the others, display absorbance into the visible region up to 440 nm. Consistently with such an absorption profile, the 8‐bromo‐7‐hydroxyquinoline‐2‐ylmethyl (BHQ) caged N ‐benzylpyrrolidine and, to a lesser extent, the 8‐iodo analog showed moderate N ‐benzylpyrrolidine release upon exposure to visible light (440 nm), candidating BHQ to further structure‐properties optimization aimed at improving visible light‐induced photorelease of tertiary amines.