Rational Design of an Electronically Gated Dicyano-BODIPY Platform for Reversible-Covalent Imaging of Methylglyoxal

High Resolution Image Download MS PowerPoint Slide Reactive α-dicarbonyls, such as methylglyoxal (MGO), are critical biomarkers of carbonyl stress, yet their real-time monitoring is stifled by a selectivity-biocompatibility paradox. Existing probes either suffer from aldehyde promiscuity, failing to distinguish dicarbonyls from the global lipid peroxidation background, or rely on high-energy, cytotoxic excitation that precludes longitudinal study. Herein, we report the rational design of a dicyano-BODIPY platform engineered to resolve this tension through a precision-tuned acceptor-photoinduced electron transfer (a-PET) mechanism. By employing density functional theory (DFT) as a predictive blueprint, we strategically depressed the BODIPY core HOMO to −6.63 eV, establishing a specific energetic gradient that enforces a robust “off” state until triggered by reversible covalent capture of α-dicarbonyls. This electronically gated design enables longitudinal, visible-light imaging of bidirectional MGO flux in living cells, a feat inaccessible to current irreversible sensors. We further demonstrate the platform’s high-fidelity performance in complex biological matrices by mapping dose-responsive MGO burden in murine brain tissue following controlled intracranial perturbation, providing a vital tool for interrogating the role of glyoxal stress in tissue-level pathologies. This work provides a generalizable electronic framework for the development of reversible-covalent sensors capable of monitoring metabolic dynamics in intact biological environments