A PET-based fluorescent probe for monitoring labile Fe(II) pools in macrophage activations and ferroptosis.

A fluorescent probe (COU-LIP-1) for monitoring labile Fe(II) pools (LIP) with high selectivity and sensitivity was developed utilizing coumarin 343 as the fluorophore and 3-nitrophenylazanyl ester as both the reactive group and the fluorescence quenching group. Fe(II)-induced reductive cleavage of the N-O bond results in a turn-on response via a photo-induced photon transfer (PET) mechanism. The probe was applied for monitoring labile iron(II) changes in M1 and M2a macrophage activations and also erastin-induced ferroptosis, providing a powerful tool for selectively sensing LIP under both physiological and stressed conditions.

Restriction of Twisted Intramolecular Charge Transfer Enables the Aggregation-Induced Emission of 1-(N,N-Dialkylamino)-naphthalene Derivatives.

Understanding the mechanisms of aggregation-induced emission (AIE) is essential for the rational design and deployment of AIEgens toward various applications. Such a deep mechanistic understanding demands a thorough investigation of the excited-state behaviors of AIEgens. However, because of considerable complexity and rapid decay, these behaviors are often not experimentally accessible and the mechanistic comprehension of many AIEgens is lacking. Herein, utilizing detailed quantum chemical calculations, we provide insights toward the AIE mechanism of 1-(N,N-dialkylamino)-naphthalene (DAN) derivatives. Our theoretical analysis, corroborated by experimental observations, leads to the discovery that modulating the formation of the twisted intramolecular charge transfer (TICT) state (caused by the rotation of the amino groups) and managing the steric hindrance to minimize solid-state intermolecular interactions provides a plausible explanation for the AIE characteristics of DAN derivatives. These results will inspire the deployment of the TICT mechanism as a useful design strategy toward AIEgen development.

Fluorescence umpolung enables light-up sensing of N-acetyltransferases and nerve agents.

Intramolecular charge transfer (ICT) is a fundamental mechanism that enables the development of numerous fluorophores and probes for bioimaging and sensing. However, the electron-withdrawing targets (EWTs)-induced fluorescence quenching is a long-standing and unsolved issue in ICT fluorophores, and significantly limits the widespread applicability. Here we report a simple and generalizable structural-modification for completely overturning the intramolecular rotation driving energy, and thus fully reversing the ICT fluorophores' quenching mode into light-up mode. Specifically, the insertion of an indazole unit into ICT scaffold can fully amplify the intramolecular rotation in donor-indazole-π-acceptor fluorophores (fluorescence OFF), whereas efficiently suppressing the rotation in their EWT-substituted system (fluorescence ON). This molecular strategy is generalizable, yielding a palette of chromophores with fluorescence umpolung that spans visible and near-infrared range. This strategy expands the bio-analytical toolboxes and allows exploiting ICT fluorophores for light-up sensing of EWTs including N-acetyltransferases and nerve agents.