Mechanism-Based Molecular Design of Highly Selective Fluorescence Probes for Nitrative Stress

Abstract

Nitrative stress is implicated in various pathogenic processes, including neurodegenerative disorders, but there is no practical fluorescence probe which can monitor the generation of nitrative stress with high selectivity. To design a suitable fluorescence probe, we have first focused on the fluorescence quenching mechanism of the nitro group, which has been believed to be a unique quencher of fluorescent dyes. We found that nitro group-based fluorescence quenching could be explained in terms of an electron transfer process, from the excited fluorophore to the electron-deficient aromatic nitro moiety. By utilizing this result, we succeeded in developing novel fluorogenic probes, NiSPYs, which can selectively monitor the generation of nitrative stress based on aromatic nitration. NiSPYs showed strong fluorescence enhancement upon the reaction with nitrating agents, including peroxynitrite, but showed little or no fluorescence augmentation in the presence of other reactive oxygen species. NiSPYs should be potentially useful as tools to study the role of nitrative stress in various biological applications.

Fluorescent probes for nitric oxide and hydrogen peroxide in cell signaling

“…We have made initial progress in the development of small-molecule ratiometric probes [37] and reversible redox sensors [38]. Finally, although this review has focused specifically on NO and H 2 O 2 indicators, new fluorogenic reagents for peroxynitrite [39], hypochlorous acid [40], superoxide [41], highly reactive oxygen species [42], and global nitrative stress [43] have also been reported recently. The continuing interplay between chemical design and biological inquiry presages a rich future for studying the oxidation biology of the cell and its contributions to human health and disease.…”

A highly selective turn-on near-infrared fluorescent probe for hydrogen sulfide detection and imaging in living cells

“…It is speculated that the fluorescence properties of the heptamethine cyanine dye could be modulated via a photoinduced electron transfer (PET) process from the excited fluorophore to a strong electron-withdrawing group (donor-excited PET; d-PET). 16 Therefore, m-nitrophenol was selected as a modulator for the Cy-NO 2 probe. After being equipped with m-nitrophenol, the fluorescence of the cyanine platform was quenched by the electron transfer process between the modulator and the fluorophore.…”

Using photochemistry to understand and control the production of reactive oxygen species in biological environments

“…4d). [50] Interestingly, NiSPYs selectivity is not the result of a specific reaction, but rather is a consequence that only chemical nitration turn the fluorescence of the reporter "on" (Fig. 4d).…”