Revisiting the Chemistry and Photophysics of 3‐(N‐Methylpyridinium‐4‐yl)Coumarins for Designing “Covalent‐Assembly” and “Molecular Disassembly” Fluorescent Probes

The double face of N -methylpyridinium moiety!!! Synthesis and photophysics of 7-(diethylamino)/7-hydroxycoumarins bearing N-methylpyridinium-4-yl group as C3 substituent were studied for identifying novel fluorophores usable in activity-based sensing approaches. The unexpected weak emissive properties of the 7-hydroxycoumarin derivative in neutral aqueous media was rationalized. Superior fluorescence performances observed with 7-(diethylamino) counterpart and ortho-formylated derivative led us to consider the design of two novel reaction-based fluorescent probes responsive to alkaline phosphatase enzyme and pyrophosphate ions respectively.

Abstract

The constant need for high-performance aniline- or phenol-based fluorophores suitable for the construction of activity-based fluorescent probes, led us to study both synthesis and photophysics of C3-N-methylpyridinium-4-yl substituted 7-(dialkylamino)/7-hydroxycoumarins. Indeed, in the field of photoactive organic molecules, the positively charged N-alkylpyridinium-4-yl groups are often used as acceptor units to dramatically impact spectral features through promoting intramolecular charge transfer (ICT) processes. They are also known as effective water-solubilizing and mitochondria targeting moieties. The poor fluorescence efficiency of cationic 7-hydroxycoumarin derivatives in aqueous physiological conditions was highlighted and rationalized by the predominance of a neutral quinonoid form in such buffer medium. The ability of the excited singlet state (S₁) of this neutral species to undergo intersystem crossing (ISC) to triplet state (T₁) was partly supported by phosphorescence measurements of singlet oxygen. We also took advantage of green-emissive properties of 7-(diethylamino)-3-(N-methylpyridinium-4-yl)coumarin to successfully design and validate a novel small-molecule fluorescent probe for the detection of alkaline phosphatase (ALP), based on the “covalent-assembly” principle. A practical use of ortho-formylated 7-hydroxy-3-(N-methylpyridinium-4-yl)coumarin was next considered with the synthesis of a Fe(III)-salen complex whose the potential as a “molecular disassembly” probe for fluorogenic sensing of pyrophosphate (PPi) anion was assessed.

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