Chemoselective Alteration of Fluorophore Scaffolds as a Strategy for the Development of Ratiometric Chemodosimeters

Abstract

Ratiometric sensors generally couple binding events or chemical reactions at a distal site to changes in the fluorescence of a core fluorophore scaffold. However, such approaches are often hindered by spectral overlap of the product and reactant species. We provide a strategy to design ratiometric sensors that display dramatic spectral shifts by leveraging the chemoselective reactivity of novel functional groups inserted within fluorophore scaffolds. As a proof-of-principle, fluorophores containing a borinate (RF620) or silanediol (SiOH2R) functionality at the bridging position of the xanthene ring system are developed as endogenous H2O2 sensors. Both these fluorophores display far-red to near-infrared excitation and emission prior to reaction. Upon oxidation by H2O2 both sensors are chemically converted to tetramethylrhodamine, producing significant (≥66 nm) blue-shifts in excitation and emission maxima. This work provides a new concept for the development of ratiometric probes.

Silicon Substitution in Oxazine Dyes Yields Near-Infrared Azasiline Fluorophores That Absorb and Emit beyond 700 nm

“… Φ (relative quantum yields) were calculated with 1,1′,3,3,3′,3′-hexamethylindotricarbocyanine iodide (HITCI) a and Cy5.5 b as standards. 2, 15, 16 ε values were rounded to the nearest thousands. …”

Borinic Acids as New Fast-Responsive Triggers for Hydrogen Peroxide Detection.

“…The absorbance evolutions as a function of pH were analyzed with the SPECFIT/32 Global Analysis System (version 3.0 for 32-bit Windows systems) to extract the pK of the investigated compounds. 8 Steady-state fluorescence emission: Corrected fluorescence spectra upon one-photon excitation were recorded with a Photon Technology International QuantaMaster QM-1 spectrofluorimeter (PTI, Monmouth Junction, NJ) equipped with a Peltier cell holder (TLC50, Quantum Northwest, Shoreline, WA). Solutions for fluorescence measurements were adjusted to concentrations such that the absorption maximum was below 0.15 at the excitation wavelength.…”

“…[4] The fluorescence of such probes is triggered or modified by H2O2-mediated transformation of a suitable chemical moiety. Several approaches have been explored including probes based on arylsulfonyl esters hydrolysis, [5] oxidation of arylboronates, [6] Baeyer-Villiger oxidation of diketones, [7] Tamao oxidation of silanes [8] or a tandem Payne-Dakin reaction. [9] Among them, probes based on the boronate esters oxidation pioneered by Chang are the most explored sensors, due to their remarkable stability, low toxicity profile, ease of preparation and their specificity towards H2O2.…”

Sensors, Imaging Agents, and Theranostics to Help Understand and Treat Reactive Oxygen Species Related Diseases

“…Li and co‐workers have developed a rhodamine‐derived probe for H 2 O 2 imaging in HeLa cells. Papkovsky and co‐workers reported a hydro‐Cy3 based fluorescent probe, which was sensitive to the mitochondrial membrane potential due to the introduction of a mitochondria targeting moiety.…”