Abstract Targeted-delivery is of great importance to molecular probes and drugs for cell biology study. Herein we reported 11 sulfur-containing coumarins as cell imaging probes. Different sulfur speciation of the 4 representative coumarins SC1-SC4 renders them significantly different subcellular localizations and cellular uptake pathways: SC1 containing thioether group located in lysosomes, while sulfoxide and sulfone compounds SC2 and SC3 distributed in the whole cell. Furthermore, the cationic sulfonium containing compound SC4 was internalized by clathrin-mediated endocytosis and localized at mitochondria. By analyzing the molecular parameters of all 11 coumarins, we found that different sulfur speciation affected their lipophilicity and electrostatic surface potential. These two key factors play roles in altering biological behaviors of the coumarins. The results revealed the importance of sulfur speciation on the physicochemical properties and thus subcellular localization of bioprobes. This is useful for designing new functional bioprobes.

中文翻译：

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硫物种定义的香豆素衍生物的亚细胞定位：结构关系与生物学行为的相关性

摘要靶向递送对于细胞生物学研究中的分子探针和药物具有重要意义。在本文中，我们报道了11种含硫的香豆素作为细胞成像探针。4种代表性香豆素SC1-SC4的不同硫形态使它们的亚细胞定位和细胞摄取途径显着不同：SC1的溶酶体中含有硫醚基，而亚砜和砜化合物SC2和SC3分布在整个细胞中。此外，通过网格蛋白介导的内吞作用将包含阳离子sulf的化合物SC4内在化，并定位于线粒体。通过分析所有11种香豆素的分子参数，我们发现不同的硫形态会影响它们的亲脂性和静电表面电势。这两个关键因素在改变香豆素的生物学行为中起作用。结果表明硫的形态对理化性质的重要性，因此对生物探针的亚细胞定位也具有重要意义。这对于设计新的功能性生物探针很有用。