New 1,2-Dihydropyridine-Based Fluorophores and Their Applications as Fluorescent Probes

Abstract

New 1,2-dihydropyridine (1,2-DHP)-based fluorophores 1a–1h were designed and synthesized by a one-pot four-component condensation reaction using dienaminodioate, aldehydes, and an in situ-generated hydrazone mediated by trifluoroacetic acid. The photophysical properties of 1,2-DHPs were studied in detail, and a few of them exhibited selective mitochondrial staining ability in HeLa cell lines (cervical cancer cells). A detailed photophysical investigation led to the design of 1,2-DHP 1h as an optimal fluorophore suitable for its potential application as a small molecule probe in the aqueous medium. Also, 1,2-DHP 1h exhibited sixfold enhanced emission intensity than its phosphorylated analogue 1h′ in the long wavelength region (λem ≈ 600 nm), which makes 1,2-DHP 1h′ meet the requirement as a bioprobe for protein tyrosine phosphatases, shown in L6 muscle cell lysate.

Lessons in Organic Fluorescent Probe Discovery

“…Lankalapalli and co-workers have reported a clever design and short synthetic route towards new fluorescent 1,2-DHPs (5 in Figure 7). [39] The synthesis of 1,2-DHP-based fluorophores was achieved by a facile one-pot four-component condensation reaction using dienaminodioates 6, aldehydes 7, and in situ-generated hydrazones 8 mediated by CF 3 CO 2 H at ambient temperature (Figure 8).…”

“…The application of these fluorophores was demonstrated for selective mitochondrial staining in HeLa cells. [39] The selectivity is based on the push-pull system in 1,2-DHPs (Figure 7), making the nitrogen within a ring attain a significant positive charge. The co-staining experiment with MitoTracker Red chloromethyl-Xrosamine (CMXRos), a commercially available mitochondria stain, confirmed the localization of 1,2-DHPs in the mitochondria, which is supported by Pearson's correlation coefficient in the range of 0.75-0.89.…”

“…Additionally, 1,2-DHP 5 d exhibited 6-fold enhanced emission intensity than its phosphorylated analogue 5 e in the long wavelength region (λ em � 600 nm), which made it a suitable bioprobe for protein tyrosine phosphatases, whose activity was demonstrated in L6 muscle cell lysate. [39]…”

A One‐pot Facile Construction of 1H‐1,2,3‐Triazolyl 1,2‐Dihydropyridyl Derivatives and Evaluation of Bioactivity Profile

“…In facrt, some 1,2‐DHP derivatives have been reported as potential anti‐cancer and antiulcer agents . More recently, these compounds are explored as potential fluorescent probes for biological applications . In addition, the triazole chemistry gaining importance in medicinal and pharmaceuticals.…”

Three-component assembly of stabilized fluorescent isoindoles

“…Conventionally, this is achieved by adding dye A to a biological molecule B, however methods have been established that generate the probe motif as part of the coupling process. 8,9 The latter, referred to as turn-on labeling, advantageously removes potential non-fluorescent impurities as only the desired product displays the proper fluorescence. While rare, advance of multicomponent turn-on labeling strategies offers a robust ability to improve the selectivity of labeling as well as to further expand the diversity possible within a labeling reaction.…”