Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California, Davis, Sacramento, California 95817, United States.
Department of Medicinal Chemistry, School of Pharmacy, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Anal Chem. 2020 Sep 15;92(18):12282-12289. doi: 10.1021/acs.analchem.0c01918. Epub 2020 Aug 25.
Small-molecule fluorescent probes are powerful tools in chemical analysis and biological imaging. However, as the foundation of probe design, the meager existing set of core fluorophores have largely limited the diversity of current probes. Consequently, there is a high demand to discover fluorophores with new scaffolds and optimize the existing fluorophores. Here, we put forward a facile strategy of heterocyclic N-oxidation to address these challenges. The introduced N-O bond reconstructs the electron "push-pull" system of heterocyclic scaffolds and dramatically improves their photophysical properties by red-shifting the spectra and increasing the Stokes shift. Meanwhile, the heterocyclic N-O bond also enables a function of the fluorescence switch. It can turn on the fluorescence of pyridine and increase the fluorescence of quinoline and, conversely, decrease the fluorescence of acridines and resorufin. As a further practical application, we successfully utilized the quinoline N-oxide scaffold to design fluorogenic probes for HS () and formaldehyde (FA, ). Given their ultraviolet-visible spectra, both probes with high selectivity and sensitivity could be conveniently used in the naked eye detection of target analytes under illumination with a portable UV lamp. More interestingly, the probes could be effectively used in the imaging of nuclear and cytoplasmic HS or nuclear and perinuclear FA. This potentially overcomes the weaknesses of existing HS or FA probes that can only work in the cytoplasm. These interesting findings demonstrate the ability to rapidly expand and optimize the existing fluorophore library through heterocyclic N-oxidation.
小分子荧光探针是化学分析和生物成像领域的有力工具。然而，作为探针设计的基础，现有的少量核心荧光团在很大程度上限制了当前探针的多样性。因此，人们迫切需要发现具有新骨架的荧光团，并优化现有的荧光团。在这里，我们提出了一种简便的杂环 N-氧化策略来应对这些挑战。引入的 N-O 键重构了杂环骨架的电子“推拉”系统，通过光谱红移和斯托克斯位移增加，显著改善了它们的光物理性质。同时，杂环 N-O 键还使荧光开关的功能成为可能。它可以打开吡啶的荧光，并增加喹啉的荧光，相反，降低吖啶和 Resorufin 的荧光。作为进一步的实际应用，我们成功地利用喹啉 N-氧化物骨架设计了用于硫氢根（HS(-)）和甲醛（FA，）的荧光探针。鉴于它们的紫外可见光谱，两种探针都具有高选择性和灵敏度，可以在便携式紫外灯下通过照射方便地用于目标分析物的肉眼检测。更有趣的是，这些探针可以有效地用于核和细胞质 HS 或核和核周 FA 的成像。这潜在地克服了现有 HS 或 FA 探针只能在细胞质中工作的弱点。这些有趣的发现表明，通过杂环 N-氧化可以快速扩展和优化现有的荧光团库。
