Pyrazole‐substituted Near‐infrared Cyanine Dyes Exhibit pH‐dependent Fluorescence Lifetime Properties

Abstract

Near-infrared heptamethine cyanine dye is functionalized with pyrazole derivatives at the meso-position to induce pH-dependent photophysical properties. The presence of pyrazole unsubstituted at 1-position is essential to induce pH-dependent fluorescence intensity and lifetime changes of these dyes. Replacement of meso-chloro group of cyanine dye IR820 with 1N-unsubstituted pyrazole resulted in the pH-dependent fluorescence lifetime changes from 0.93 ns in neutral media to 1.27 ns in acidic media in DMSO. Time resolved emission spectra (TRES) revealed that at lower pH, the pyrazole consists of fluorophores with two distinct lifetimes, which corresponds to pH sensitive and non-pH sensitive species. In contrast, 1N-substituted pyrazoles do not exhibit pH response, suggesting excited state electron transfer as the mechanism of pH-dependent fluorescence lifetime sensitivity for this class of compounds.

Cyanine polyene reactivity: scope and biomedical applications

“…71 Compound 21 displays a fairly complex pH profile, likely due to the presence of two titratable protons, with a useful 10-fold increase in fluorescence intensity within a pH range of 4.0-6.5. 73 The cellular internalization of many tumor-targeting agents is accompanied by significant reduction of the local pH as the targeting agent/receptor complex is trafficked through endosomal compartments to the lysosome. 3B).…”

Synthesis of nitric oxide probes with fluorescence lifetime sensitivity

“…16 Fluorescence lifetime of polymethine probes is, in general, sensitive to the environment and structural modifiers. 9-11 Placing electron rich amines in close proximity to the fluorophore decreases the emission due to photoinduced electron transfer (PET) 21 also known as excited state electron transfer (ESET) effect that results in the lower fluorescence lifetime.…”

“…10, 11 Additional benefits of fluorescence lifetime includes contrast enhancement through alleviation of some of the typical problems associated with intensities including scattering, 12 sample turbidity, and autofluorescence. 13-15 Recently, several papers describing lifetime sensitive probes based on cyanine dyes, 16, 17 quantum dots 18, 19 and fluorescent proteins 20 have been published.…”

Rational Molecular Design and Synthesis of Highly Thermo‐ and Photostable Near‐Infrared‐Absorbing Heptamethine Cyanine Dyes with the Use of Fluorine Atoms

“…The Stokes shifts of 1 – 3 are similar and all fall between 28 and 32 nm. In MeOH, the relative fluorescence quantum yields ( Φ ) of 1 and 2 a are slightly higher, and those of 2 b and 3 a,b are slightly lower, compared with that of the reference dye (indocyanine green (ICG) Φ= 0.09) . The lifetimes of the prepared dyes in MeOH are shorter than that of ICG (0.52)…”

“…In MeOH,t he relative fluorescence quantum yields (F)o f1 and 2a are slightly higher,a nd those of 2b and 3a,b are slightly lower,c ompared with that of the reference dye (indocyanine green (ICG) F = 0.09). [11,12] The lifetimes of the prepared dyes in MeOH are shortert han that of ICG (0.52). [12] Thermogravimetric differential thermal analysis( TG-DTA) measurements were performed to determine the decomposition temperatures (T dt )o ft he heptamethine cyanine dyes 1-3.…”