A Unique Class of Near-Infrared Functional Fluorescent Dyes with Carboxylic-Acid-Modulated Fluorescence ON/OFF Switching: Rational Design, Synthesis, Optical Properties, Theoretical Calculations, and Applications for Fluorescence Imaging in Living Animals
A Unique Class of Near-Infrared Functional Fluorescent Dyes with Carboxylic-Acid-Modulated Fluorescence ON/OFF Switching: Rational Design, Synthesis, Optical Properties, Theoretical Calculations, and Applications for Fluorescence Imaging in Living Animals
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DOI：
10.1021/ja209292b
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发表时间：
2012-01-18
影响因子：
15
通讯作者：
Chen, Hua
中科院分区：
文献类型：
--
作者：
Yuan, Lin;Lin, Weiying;Chen, Hua
荧光成像是监测生命系统中生物分子的最强大的技术之一。近红外区吸收和发射的荧光传感器有利于生物成像。在活体动物中的应用，因为近红外光导致最小的光损伤，深层组织穿透和最小的背景自发荧光干扰。在这里，我们介绍了一种新的策略，通过螺环反应来设计具有羧酸可控荧光开关机制的近红外功能染料。基于这一设计策略，我们开发了一系列长沙(CS1-6)近红外荧光团，这是一类独特的新型近红外功能荧光染料，具有良好的光物理性能，包括吸收消光系数大、荧光量子产率高、亮度高、光稳定性好和足够的化学稳定性。值得注意的是，新的CS1-6近红外染料在近红外区域的吸收和发射都优于传统的罗丹明染料，同时保留了类似罗丹明的荧光开关机制。此外，我们用6-31G*基组的B3LYP交换泛函进行了量子化学计算，揭示了新的CS1-6近红外染料的结构和光学性质。此外，以CS2为平台，我们进一步构建了新型的近红外荧光开启传感器7，该传感器能够对活体动物体内内源性产生的HCIO进行成像，展示了我们新的CS近红外功能荧光染料的价值。我们希望该设计策略可以扩展到开发具有合适的荧光控制机制的多种近红外功能染料，以用于生物学研究中的许多有用的应用。
Fluorescence imaging is one of the most powerful techniques for monitoring biomolecules in living systems. Fluorescent sensors with absorption and emission in the near-infrared (NIR) region are favorable for biological imaging . applications in living animals, as NIR light leads to minimum photodamage, deep tissue penetration, and minimum background autofluorescence interference. Herein, we have introduced a new strategy to design NIR functional dyes with the carboxylic-acid-controlled fluorescence on off switching mechanism by the spirocyclization. Based on the design strategy, we have developed a series of Changsha (CS1-6) NIR fluorophores, a unique new class of NIR functional fluorescent dyes, bearing excellent photophysical properties including large absorption extinction coefficients, high fluorescence quantum yields, high brightness, good photostability, and sufficient chemical stability. Significantly, the new CS1-6 NIR dyes are superior to the traditional rhodamine dyes with both absorption and emission in the NIR region while retaining the rhodamine-like fluorescence ON-OFF switching mechanism. In addition, we have performed quantum chemical calculations with the B3LYP exchange functional employing 6-31G* basis sets to shed light on the structure-optical properties of the new CS1-6 NIR dyes. Furthermore, using CS2 as a platform, we further constructed the novel NIR fluorescent TURN-ON sensor 7, which is capable of imaging endogenously produced HCIO in the living animals, demonstrating the value of our new CS NIR functional fluorescent dyes. We expect that the design strategy may be extended for development of a wide variety of NIR functional dyes with a suitable fluorescence-controlled mechanism for many useful applications in biological studies.