Development of a Redox‐Responsive Polymeric Profluorescent Probe

Abstract

Profluorescent nitroxides (PFNs) have emerged as an important class of imaging agents for monitoring intracellular redox status and levels of oxidative stress. However, the fast reduction of nitroxides upon incubation within cells limits the window of opportunity for detection. By increasing the concentration of nitroxides per fluorophore, their reduction to the corresponding hydroxylamines and the subsequent switch‐on of fluorescence can be delayed. Herein the preparation of nitroxide‐containing polymers of different chain length coupled to a fluorophore is reported and their reduction with pentafluorophenylhydrazine is examined. The fluorescence switch‐on kinetics and radical concentrations are monitored by fluorescence and electron paramagnetic resonance spectroscopy and compared to a conventional PFN bearing a single nitroxide moiety. The polymeric PFNs display significant delays in reduction and fluorescence switch‐on and higher turn‐on ratios than their single‐nitroxide counterparts. The results of this study indicate that polymeric PFNs are a promising architecture for future imaging agents.

BODIPY‐Based Profluorescent Probes Containing Meso‐ and β‐Substituted Isoindoline Nitroxides

“…The use of PFPH was preferred over phenylhydrazine because it is less prone to oxidation and is therefore more suitable for use in non‐deoxygenated solvents under atmospheric conditions that are more relevant to biological systems. The use of tandem EPR and fluorescence spectroscopy for analysis of profluorescent nitroxides has recently been reported and allows the quantification of radical concentration whilst fluorescence is monitored by a fibre‐optic probe, minimising external influences affecting individual measurements, such as variable oxygen concentrations.…”

Chemical design and synthesis of macromolecular profluorescent nitroxide systems as self-reporting probes

“…Critically, polymeric profluorescent systems are relatively less-investigated, but are quite an attractive subject of recent research. 37,38 Intriguingly, a recent literature survey indicated that the potential of macromolecular nitroxide derivatives as new functional handles for use as self-reporting probes has not been reviewed critically.…”

“…They compared the quenching efficiency and reducing behaviour of small-molecule profluorescent nitroxides and their macromolecular equivalents (Scheme 6). 38 The synthesis of the small molecule was straightforward, but the nitroxide could not be introduced directly in the polymer backbone because the radical species would have interfered with the controlled radical polymerization that was employed. Therefore, the polymer was generated by polymerizing 2,2-6,6-tetramethyl piperidinyl methacrylate (TMPM) via atom-transfer radical polymerization (ATRP) and subsequent oxidation of the amine functional group using mCPBA.…”

A Methoxyamine‐Protecting Group for Organic Radical Battery Materials—An Alternative Approach

“…Organic radical polymers have received significant attention over the last two decades because of their redox‐active nature and found wide‐ranging application in a variety of fields including catalysis, spin probes, imaging agents, antibiofilm coatings, and most prominently of all, as electroactive materials in organic radical batteries (ORB) . The current trend towards renewable energy and increased environmental awareness has boosted research into organic‐based materials for energy applications promising safer, more powerful and environmentally friendly technologies .…”