Synthesis, stability and spectral behavior of fluorogenic sulfone-pyronin and sulfone-rosamine dyes

Abstract

The first synthesis of sulfone-pyronin and sulfone-rosamine dyes bearing optically tunable primary amino groups (acting as fluorogenic centers) is presented. Sulfone analogs of xanthene-based fluorophores have recently been highlighted as a new class of near-infrared (NIR) fluorescent dyes (Liu et al. ACS Appl Mater Interfaces 2016;8(35):22953-62), and the availability of fluorogenic derivatives is essential for the rapid construction of "turn-on" reactive probes for chemoselective bioimaging. However, these fluorescent anilines have been found to be unstable in aqueous physiological conditions due to the marked electrophilicity of their meso-position and hence its propensity to undergo nucleophilic attack by a water molecule or a hydroxyde anion. Further investigations have helped us to determine the acidic pH range at which the sulfone-rosamine 2 is fully-stable and a complete assessment of the photophysical properties could be performed. Its pro-fluorescent character and utility were then proved by the preparation and in vitro enzymatic activation of a penicillin G acylase (PGA) sensitive fluorogenic probe.

Quest for novel fluorogenic xanthene dyes: Synthesis, spectral properties and stability of 3-imino-3H-xanthen-6-amine (pyronin) and its silicon analog

“…1 TFA per molecule of fluorophore) in freeze-dried sample was determined by ion chromatography. 26 Scheme 1. Synthesis of fluorogenic pyronin 1 (purification protocol revisited).…”

“…12,24,27,28 Contrary to silicon-containing dyes previously published, the lack of alkyl substituents in both amino groups necessarily implies the temporary protection of primary anilines. By analogy with the synthetic routes towards siliconfluorescein and sulfone-rosamine, respectively published by the Hanaoka group 29 and us 26 , the allyl moiety was used as protecting group (both to remove NH "acidic" protons and to enhance solubility of intermediates in organic solvents) that is stable under a variety of conditions (especially in the presence of RLi/ArLi) and easily removed by Pd(0)-catalysis under mild and neutral conditions.…”

Synthesis of Pyridyl and N‐Methylpyridinium Analogues of Rosamines: Relevance of Solvent and Charge on Their Photophysical Properties

“…In contrast, the fluorescence behavior is also controlled by an intramolecular photoinduced electron transfer (PET) mechanism through which the fluorescence of the fluorophore is quenched by an electron transfer from the donor carboxylate to the acceptor xanthene (Figure a). The elucidation of these mechanisms of fluorescence has arisen the interest in the synthesis of new rhodamine derivatives with increased optical properties . Major contributions in this field include: (i) the strategy proposed by Lavis’ group to improve the brightness and photostability of compounds by mitigating the TICT status, which consists in the incorporation of four‐membered azetidine rings into fluorescent scaffolds (at 3‐ and 6‐positions); (ii) inclusion of bulky and electronically inert substituents at the aryl ring or by rigidification of the molecular skeleton, and (iii) substitution of the oxygen atom of the xanthene by silicon, through a PET strategy developed by Nagano's group .…”

“…The elucidation of these mechanisms of fluorescenceh as arisen the interesti nt he synthesis of new rhodamine derivatives with increased optical properties. [14,15] Major contributionsi nthis field include:( i) the strategyp roposed by Lavis' group to improve the brightness and photostability of compoundsb ym itigating the TICT status, [16] which consistsi nt he incorporation of four-membered azetidine rings into fluorescent scaffolds (at 3-and 6-positions);( ii)inclusion of bulky and electronically inert substituents at the aryl ring or by rigidification of the molecular skeleton, [17,18] and (iii)substitutiono ft he oxygen atom of the xanthene by silicon, through aP ET strategyd eveloped by Nagano's group. [6,19] These and other recent advances in chemical modifications of rhodamine skeleton have been comprehensively reviewed in several articles, which also include examples of their application as fluorescent probesf or targeting biological and environmental important analytes.…”

A Novel Enzyme-Triggered Domino Reaction Producing Fluorescent Quinoxalin-2(1H)-One-Based Heterocycles

“…TFA mass content of samples purified by semi-preparative was determined by ion chromatography according to a method developed by the PACMSUB staff. 2 Such analyses were performed with an ion chromatograph Thermo Scientific Dionex ICS 5000 equipped with a conductivity detector CD (Thermo Scientific Dionex) and a conductivity suppressor ASRS-ultra II 4 mm (Thermo Scientific Dionex). Low-resolution mass spectra (LRMS) were recorded on a Thermo Scientific MSQ Plus single quadrupole equipped with an electrospray (ESI) source (LC-MS coupling mode).…”