Analytical Sciences

The Utility of Sonogashira Coupling Reaction for the Derivatization of Aryl Halides with Fluorescent Alkyne

Naoyuki YASAKA, Naoya KISHIKAWA, Takumi HIGASHIJIMA, Kaname OHYAMA, and Naotaka KURODA

Graduate School of Biomedical Sciences, Course of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan

Aryl halides are a very important category of compounds that include many vital drugs and key industrial additives, such as clofibrate and bromobenzene, respectively. Due to their importance, our research group previously developed a novel fluorescence labeling approach for their analysis using a fluorescent aryl boronic acid as a reagent, based on the Suzuki coupling reaction. This coupling reaction was successfully applied for the determination of aryl halides in biological fluids; however, there was a limitation of low reactivity towards ortho-substituted aryl halides. In the present study, a novel fluorescence derivatization approach for aryl halides was developed using, 2-(4-ethynylphenyl)-4,5-diphenyl-1H-imidazole (DIB-ET) as a fluorescent alkyne reagent, based on the Sonogashira coupling reaction. DIB-ET reacted with aryl bromides in the presence of palladium and copper as catalysts, yielding fluorescent derivatives that could be subsequently determined by an HPLC system with fluorescence detection. The detection limits (S/N = 3) for aryl bromides were in the range of 14 – 23 nM, which is 3.5 – 18-times more sensitive than our previously developed approach, Suzuki coupling derivatization. Moreover, in contrast to the previous technique, the reactivity of DIB-ET to ortho-substituted aryl bromides was almost equivalent to that of the para-substituted aryl bromides. Hence, by using this newly developed approach we could label the aryl halides with more sensitivity and reactivity. Finally, the proposed method was successfully applied for the selective determination of aryl bromides in human serum with good recovery (84.6 – 107%), which proves the ability of the developed method to determine occupational exposure to aryl halides.

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