NIR Mega‐Stokes Fluorophores for Bioorthogonal Labeling and Energy Transfer Systems–An Efficient Quencher for Daunomycin

Abstract

A set of new azide- and alkyne-bearing lepidinium-based fluorophores were synthesized for bioorthogonal labeling schemes. These fluorescent dyes all show large Stokes-shifts with emission maxima in the near-infrared (NIR) region of the electromagnetic spectrum. The applicability of these dyes in the construction of energy-transfer systems was tested using one of these new fluorescent tags and daunomycin (Dau), an anticancer drug with fluorescent features. These daunomycin conjugates are the very first examples of fluorescently modulated constructs of this anticancer agent. The dually labeled architectures proved that the applied fluorescent dye can be utilized as an efficient quencher for daunomycin. Enzymatic cleavage of a dually labeled enzyme substrate resulted in full recovery of the fluorescence of daunomycin. Such fluorescently modulated Dau conjugates can provide useful information for the mechanism of action of Dau-regulated cell death processes.

Bioorthogonal fluorescent labels: a review on combined forces

“…Another common issue in fluorescent imaging techniques, especially in FRET applications is the small Stokes-shift of the probes. Kele and co-workers [67,68] synthesized a series of dyes with large Stokes-shifts based on a stilbene motif ( Figure 9). The labels were furnished with alkyne and/or azide as a bioorthogonal functionality and their emission ranged from 630 nm to 805 nm, covering the spectra from the red to the NIR regime.…”

1-(3-Iodopropyl)-4-methylquinolin-1-ium Iodide

“…In general, residues of the dimer side product 4 can be observed when using lower proportions of 4-methylquinoline and 1,3-diiodopropane. Even by heating, which usually takes up to 18-20 hours based on reported methods, the reaction mixture does not necessarily prevent the formation of any by-products [10][11][12]. Furthermore, we found that the total yield can considerably be enhanced by adding extra equimolar amounts of the starting materials to the filtrate.…”

Polarity Sensitive Bioorthogonally Applicable Far-Red Emitting Labels for Postsynthetic Nucleic Acid Labeling by Copper-Catalyzed and Copper-Free Cycloaddition

“…In the design process we aimed to develop bioorthogonally conjugatable, polarity sensitive labels with polar characteristics in order to minimize the possibility of nonspecific sticking to hydrophobic surfaces. As a starting point, we used frameworks (Figure ) that we formerly found amenable to conjugation mediated fluorescence turn on. , It was hypothesized that replacement of the lepidinium core of dyes 1a , b with more polar ethyl-benzothiazolium unit ( 2a , b ) would substantially increase polarity.…”