A Cyanine Photooxidation/ß-Elimination Sequence Enables Near-infrared Uncaging of Aryl Amine Payloads.

ABSTRACT

Uncaging strategies that use near-infrared wavelengths can enable the highly targeted delivery of biomolecules in complex settings. Many methods, including an approach we developed using cyanine photooxidation, are limited to phenol-containing payloads. Given the critical role of amines in diverse biological processes, we sought to use cyanine photooxidation to initiate the release of aryl amines. Heptamethine cyanines substituted with an aryl amine at the C4' position undergo only inefficient release, likely due electronic factors. We then pursued the hypothesis that the carbonyl products derived from cyanine photooxidation could undergo efficient ß-elimination. After examining both symmetrical and unsymmetrical scaffolds, we identify a merocyanine substituted with indolenine and coumarin heterocycles that undergoes efficient photooxidation and aniline uncaging. In total, these studies provide a new scheme-cyanine photooxidation followed by ß-elimination-through which to design photocages with efficient uncaging properties.