NIR-Ⅱ荧光分子CH1055的合成及光学特征研究

Synthesis and optical characteristics of near infrared-Ⅱ fluorescent molecule CH1055

目的对荧光分子CH1055的合成方法进行探索与优化,并对其水溶性及光学特性进行初步研究。方法以三苯胺和苯并噻二唑为起始原料,经Vilsmeier-Haack反应、酰化、催化氢化、Suzuki偶合等一系列反应得到目标产物,中间体及目标化合物的结构经MS和1H NMR确证。同时,优化关键反应步骤,并对其溶解度及体内外光学特性进行研究。结果改进合成方法后,反应总收率从文献报道的9.13%提高至12.1%。聚乙二醇化修饰后的产物,水溶性提升约300倍。在750 nm激发波长下,CH1055比传统的Cy5.5具有更好的成像特性。结论优化后的CH1055合成方法原料价廉易得,操作简便,且提高了收率。经聚乙二醇化修饰后,目标化合物水溶性大大提高,有利于开发水溶性良好的NIR-Ⅱ荧光分子。CH1055在长波长范围内具有优异的成像特性,为该荧光分子尝试不同的应用提供了新思路。

Objective To optimize the synthetic method for the fluorescent molecule CH1055 and perform a preliminary study on its water solubility and optical properties. Methods Starting from triphenylamine and benzothiadiazole,the desired products were synthesized via a series of reactions,such as Vilsmeier-Haack reaction,acylation,catalytic hydrogenation,bromination,condensation,silylation protection,Suzuki coupling,nitrification and reduction. The structures of the intermediates and targeted compound were confirmed by MS and1 H NMR. At the same time,the key reaction steps were optimized,and the solubility and optical properties of CH1055 were investigated both in vitro and in vivo. Results After improvement of the synthetic method,the total yield increased from 9.13% in the literature to 12.1% in the present study. The PEGylated product improved water solubility by about 300 times. At the wavelength of 750 nm long excitation light,CH1055 had better imaging characteristics than the traditional Cy5.5. Conclusion The present method for the CH1055 synthesis has appeared to be cheaper in cost,easy to operate,and higher in yield. After PEGylation modification,the water solubility of the target compound was greatly improved,which was highly advantageous to the development of a water-soluble NIR-Ⅱ fluorescent molecule. CH1055 showed excellent imaging properties in the long wavelength range,which implicated a new potential application of the fluorescent molecule.