Development of a 1,3a,6a-triazapentalene derivative as a compact and thiol-specific fluorescent labeling reagent

Abstract

For the fluorescence imaging of biologically active small compounds, the development of compact fluorophores that do not perturb bioactivity is required. Here we report a compact derivative of fluorescent 1,3a,6a-triazapentalenes, 2-isobutenylcarbonyl-1,3a,6a-triazapentalene (TAP-VK1), as a fluorescent labeling reagent. The reaction of TAP-VK1 with various aliphatic thiols proceeds smoothly to afford the corresponding 1,4-adducts in high yields, and nucleophiles other than thiols do not react. After the addition of thiol groups in dichloromethane, the emission maximum of TAP-VK1 shifts to a shorter wavelength and the fluorescence intensity is substantially increased. The utility of TAP-VK1 as a compact fluorescent labeling reagent is clearly demonstrated by the labeling of Captopril, which is a small molecular drug for hypertension. The successful imaging of Captopril, one of the most compact drugs, in this study demonstrates the usefulness of compact fluorophores for mechanistic studies.

Pyrazolo[1,5-a]pyrimidines-based fluorophores: a comprehensive theoretical-experimental study

“…The fact that the f F values in uorophores 4f and 4g are remarkably high in solvents of different polarity is a notable virtue that can be useful, for example, in monitoring macromolecules dynamics 5 or labeling pharmacological targets. 3 Interestingly, these probes displayed good emission intensities even in polar solvents such as ethanol-water 4 : 1 or THF-water mixtures (Fig. S3 †), which is a remarkable property for biological applications.…”

“…Fluorescent organic compounds have been a major focus of research related to materials science and biological interactions over the past decades. 1 Ranging from ionic or molecular sensing 2 to bioimaging applications 3 and, from the organic light-emitting devices, 4 bio-macromolecular interactions. 5 A plethora of applications has been proposed by exploiting the benecial properties of such materials that can raise our standard of living.…”

“…Because a probe for bioimaging is inherently involved in complex biological interactions within the cell, the probe must be as small as possible to reduce its impacts on the biological dynamics and facilitate its diffusion inside the cell organelles. 3 Likewise, for most of the photophysical applications, the uorophore must be able to change its absorption and emission properties with small and simple chemical modications. Ful-lling the above-mentioned conditions in a single uorophore is a challenging task and many efforts need to be made in this direction.…”

Pyridazino-1,3a,6a-Triazapentalenes as Versatile Fluorescent Probes: Impact of Their Post-Functionalization and Application for Cellular Imaging

“…Small-organic fluorophores have become tools of major importance for biological, biochemical and biomedical research but also for diagnosis [ 1 , 2 , 3 ]. Recently added in this field, 1,3a,6a-triazapentalene (TAP) has emerged and its uses as probes [ 4 , 5 , 6 ] or sensors [ 7 ] has been tested. Therefore, extensive synthetic studies have been reported on the 5/5 bicyclic scaffold in order to introduce structural diversities in order to improve its fluorescent property and/or its chemical stability [ 8 ].…”

Ring-Degenerate Rearrangement Resulting from the Azo Coupling Reaction of a 3-Aryl-1,3a,6a-triazapentalene

“…The 1,3a,6a-triazapentalene ( TAP ) has emerged as a new small molecule fluorophore over the past decade, − and the applications of some derivatives as probes or sensors have been recently explored. − In particular, triazapentalenes without an additional fused ring have been studied extensively by Namba et al, revealing interesting properties such as a large Stokes shift and strong positive solvatochromism. ,,− The synthetic methodology of Namba et al comprises a click–cyclization–aromatization domino reaction, using alkyl azides bearing two leaving groups, and leads to 3-unsubstituted (Scheme ) triazapentalenes. In this way, structural diversity resulted from the variation of terminal alkynes and the starting azide, which required a multistep synthesis.…”