Wills Rachel, Farhi Jonathan, Czabala Patrick, Shahin Sophia, M Spangle Jennifer, Raj Monika
Department of Chemistry, Emory University Atlanta GA USA
Department of Radiation Oncology, Winship Cancer Institute of Emory University School of Medicine Atlanta GA USA.
Chem Sci. 2023 Jul 19;14(31):8305-8314. doi: 10.1039/d3sc02025h. eCollection 2023 Aug 9.
Aliphatic aldehydes are reactive electrophilic carbonyls that cross-link with DNA and proteins leading to cellular toxicity and disease pathogenesis. This toxicity is due to the cooperative effect of multiple aldehydes a common mechanism. Therefore, live-cell imaging of total aliphatic aldehydes, small-to-long chain (C-C), is highly desired to decipher their physiological and pathological functions. However, sensors for imaging total cellular aliphatic aldehydes are currently lacking despite their high concentrations (∼80 to >500 μM) inside cells. Herein, we report chemical sensors that generate a benzimidazole moiety upon reaction with aliphatic aldehydes of different chain lengths (C-C), resulting in turn-on fluorescence. These sensors exhibit high quantum yields, high dynamic range, and enable the quantification of changes in both the exogenous administration of aldehydes and endogenous real-time formation of aliphatic aldehydes in live mammalian cells. This tool has great potential to transform aldehyde research by illuminating cellular metabolites that have remained elusive in living systems.
脂肪醛是具有反应活性的亲电羰基化合物，可与DNA和蛋白质发生交联，导致细胞毒性和疾病发病机制。这种毒性是多种醛协同作用的结果，这是一种常见机制。因此，人们非常希望能够对全链脂肪醛（从小链到长链，C-C）进行活细胞成像，以解读它们的生理和病理功能。然而，尽管细胞内全链脂肪醛的浓度很高（约80至>500 μM），但目前仍缺乏用于对其进行成像的传感器。在此，我们报告了一种化学传感器，该传感器在与不同链长（C-C）的脂肪醛反应时会生成苯并咪唑部分，从而产生荧光开启现象。这些传感器具有高量子产率、高动态范围，能够对外源性醛给药和活的哺乳动物细胞内脂肪醛的内源性实时形成的变化进行定量。该工具通过揭示生命系统中难以捉摸的细胞代谢物，在改变醛研究方面具有巨大潜力。
