Redesigning the Coumarin Scaffold into Small Bright Fluorophores with Far-Red to Near-Infrared Emission and Large Stokes Shifts Useful for Cell Imaging,The Journal of Organic Chemistry

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Redesigning the Coumarin Scaffold into Small Bright Fluorophores with Far-Red to Near-Infrared Emission and Large Stokes Shifts Useful for Cell Imaging
The Journal of Organic Chemistry ( IF 3.3 ) Pub Date : 2018-01-11 00:00:00 , DOI: 10.1021/acs.joc.7b02660
Albert Gandioso _{1,

2} , Roger Bresolí-Obach ₃ , Alba Nin-Hill _{1,

4} , Manel Bosch ₅ , Marta Palau ₁ , Alex Galindo ₁ , Sara Contreras ₁ , Anna Rovira ₁ , Carme Rovira _{1,

4,

6} , Santi Nonell ₃ , Vicente Marchán _{1,

2}

Affiliation

Among the palette of previously described fluorescent organic molecules, coumarins are ideal candidates for developing cellular and molecular imaging tools due to their high cell permeability and minimal perturbation of living systems. However, blue-to-cyan fluorescence emission is usually difficult in in vivo applications due to the inherent toxicity and poor tissue penetration of short visible light wavelengths. Here, we introduce a new family of coumarin-based fluorophores, nicknamed COUPY, with promising photophysical properties, including emission in the far-red/near-infrared (NIR) region, large Stokes shifts, high photostability, and excellent brightness. COUPY fluorophores were efficiently synthesized in only three linear synthetic steps from commercially available precursors, with the N-alkylation of a pyridine moiety being the key step at the end of the synthetic route, as it allows for the tuning of the photophysical properties of the resulting dye. Owing to their low molecular weights, COUPY dyes show excellent cell permeability and accumulate selectively in nucleoli and/or mitochondria of HeLa cells, as their far-red/NIR fluorescence emission is easily detected at a concentration as low as 0.5 μM after an incubation of only 20 min. We anticipate that these coumarin scaffolds will open a way to the development of novel coumarin-based far-red to NIR emitting fluorophores with potential applications for organelle imaging and biomolecule labeling.

中文翻译：

将香豆素支架重新设计成小的亮荧光团，具有远红至近红外发射以及对细胞成像有用的大斯托克斯频移

在先前描述的荧光有机分子的调色板中，香豆素因其高的细胞渗透性和对生命系统的最小干扰而成为开发细胞和分子成像工具的理想候选者。然而，由于短时可见光波长的固有毒性和不良的组织穿透性，在体内应用中蓝光至青色荧光发射通常是困难的。在这里，我们介绍了一个新的基于香豆素的荧光团家族，绰号为COUPY，它具有良好的光物理特性，包括远红/近红外（NIR）区域的发射，大的斯托克斯频移，高的光稳定性和出色的亮度。COUPY荧光团仅需三个线性合成步骤即可从市售前体中高效合成，其中N吡啶部分的-烷基化是合成路线末端的关键步骤，因为它可以调节所得染料的光物理性质。由于其低分子量，COUPY染料显示出优异的细胞通透性，并选择性地聚集在HeLa细胞的核仁和/或线粒体中，因为它们的远红外/ NIR荧光发射很容易在低至0.5μM的浓度下检测到。仅20分钟。我们预计这些香豆素支架将为开发新的基于香豆素的远红外至近红外发射荧光团开辟道路，并有望在细胞器成像和生物分子标记中应用。

更新日期：2018-01-11

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