Department of Chemistry, University of Otago, Dunedin, New Zealand.
Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
Org Biomol Chem. 2022 Jul 27;20(29):5812-5819. doi: 10.1039/d2ob01076c.
The synthesis of the fluorescent organic carbon monoxide releasing molecules oCOm-57, oCOm-58, and oCOm-66 are reported. These oCOms are water soluble and exhibit a "turn-on" fluorescent behaviour when CO is released under physiological conditions. oCOm-66 also contains an additional nitro-naphthalimide moiety that functions as a fluorescent reporter. Delivery of CO released from these oCOms to the mitochondria of AC-16 cardiomyocytes was confirmed using confocal microscopy in conjuction with MitoTracker Red. While the neutral, PEGylated oCOm-57 was found to remain in the extracellular environment releasing CO to diffuse into the cellular compartments, the positively charged oCOm-58 and -66 are targeted to the mitochondria where they release CO. Notably, the use of the fluorescent oCOms in live cellular imaging, allows the intracellular CO delivery and oCOm localisation to be characterised. This cellular confocal study also shows that, subtoxic concentrations of CO released from these molecules preserved mitochondrial energetics as indicated by the membrane potential dependent MitoTracker Red.
报道了荧光有机一氧化碳释放分子 oCOm-57、oCOm-58 和 oCOm-66 的合成。这些 oCOm 水溶性好，在生理条件下释放 CO 时表现出“开启”荧光行为。oCOm-66 还含有一个额外的硝基萘酰亚胺部分，用作荧光报告器。使用共聚焦显微镜结合 MitoTracker Red 证实了从这些 oCOm 释放的 CO 递送到 AC-16 心肌细胞的线粒体中。虽然中性、PEG 化的 oCOm-57 被发现仍留在细胞外环境中，释放 CO 扩散到细胞隔室中，但带正电荷的 oCOm-58 和 -66 则靶向线粒体，在那里释放 CO。值得注意的是，荧光 oCOm 在活细胞成像中的使用允许对细胞内 CO 传递和 oCOm 定位进行特征描述。这项细胞共聚焦研究还表明，这些分子释放的亚毒性浓度的 CO 保持了线粒体的能量状态，如依赖于膜电位的 MitoTracker Red 所示。
