Synthetic Routes to Novel Fluorogenic Pyronins and Silicon Analogs with Far-Red Spectral Properties and Enhanced Aqueous Stability

Abstract

Fluorogenic detection of reactive (bio)analytes is often achieved with "smart" probes, whose activation mechanism causes the release of aniline-based fluorophores. Indeed, the protection-deprotection of their primary amino is the simplest way to induce dramatic and valuable changes in spectral features of the fluorogenic reporter. In this context, and due to their small size and intrinsic hydrophilicity, we focused on pyronin dyes and related heteroatom analogs (i.e., formal derivatives of 3-imino-3H-xanthen-6-amine and its silicon analog) for their use as optically tunable aniline-based fluorophores. To overcome some severe limitations associated with the use of such fluorogenic scaffolds (i.e., poor aqueous stability and spectral features only in the green-yellow spectral range), the synthesis of novel unsymmetrical derivatives of (Si)-pyronins bearing a single bulky tertiary aniline (i.e., N-methylindoline and julolidine) was explored and presented in this Article. This structural alteration has been found to be beneficial to dramatically lower electrophilicity of the meso-position and to reach attractive fluorescence properties within the far-red spectral region.

Xanthene dyes for cancer imaging and treatment: A material odyssey

“…In the light of poor aqueous stability of the primary amines at the Siand SO 2 -Pyronines at physiological pH, Dejouy and coworkers designed unsymmetrical Si-pyronines (MeISi-Pyronin, JSi-Pyronin, Table 7:E19-20, Scheme 11), which consist of tertiary amine on one side (N-methylindoline and julolidine) and primary amine on the other. [99] Consequently, electron donation of the tertiary amine led MeISi-Pyronin and JSi-Pyronin to have optimal stability in an aqueous medium up to pH=7 and pH=8, respectively (its primary amine analog does up to pH:5) as well as keeps the rigidity of the xanthene skeleton for higher fluorescence quantum efficiency. Secondly, since primary amine sides at MeISi-Pyronin and JSi-Pyronin can be modified with targeting units, these systems were called "smart" probes.…”