A Cyanine Photooxidation/β‐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 0 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 b-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 b-elimination-through which to design photocages with efficient uncaging properties.

Shining a Light on Bioorthogonal Photochemistry for Polymer Science

“…The group of Schnermann has exploited the photooxidation of NIR absorbing cyanine dyes, to generate a range of photocleavable linkers, which can be used to construct photolabile antibody-drug conjugates (ADC). [28,113,114] Irradiation leads to cyanine photooxidation, formation of a dioxetane ring on the heptamethine bridge and subsequent cleavage to a conjugated Figure 6. Molecular design of a 2PA dyad capable of acetic acid (red) release, combining a nitroindolinyl photocage (pink) and a dissymmetric 2PA chromophore (blue).…”

Cyanine Modification Tuned for Amine Photorelease

“…A cyanine conjugate designed for aryl amine photorelease conducted by Schnermann et al . provides insight into this very reaction.…”

“…The work of Schnermann et al . is a key initial step with the advent of NIR‐absorbing cyanine conjugates to photorelease aryl amines. It has been shown that the reaction involves the photorelease of anilines, but it is conceivable that new cyanine conjugates will serve as a pathway to the photorelease of other amine compounds.…”

“…A b-elimination strategy following cyanine photooxidation has resulted in an amine photorelease reaction. A cyanine conjugate designed for aryl amine photorelease conducted by Schnermann et al (1) provides insight into this very reaction.…”

Cyanine Nanocages Activated by Near-Infrared Light for the Targeted Treatment of Traumatic Brain Injury

“…Heptamethine cyanine dyes were traditionally used as reporter molecules that bind to biomolecules such as proteins, RNA, and DNA (Lipowska et al, 1993;Williams et al, 1993Williams et al, , 1997Shealy et al, 1995;Christian Mason et al, 1997;Sowell et al, 2001a,b;Strekowski et al, 2001;Patonay et al, 2004;Luciano et al, 2019). More recently, the use of a cyanine dye as a photoactivated nanocage for targeted drug release has been reported by Gorka et al 2014, Nani et al (2015aNani et al ( ,c, 2017, Sato et al (2015Sato et al ( , 2016, Patel et al (2016) and Yamamoto et al (2019). Cyanine dyes offer several advantages such as maximum absorbances in the NIR window (650-900 nm), low background absorbance interference, and low toxicity (Marshall et al, 2010;Donald et al, 2011).…”