A thiourea dihydropyridine as a highly selective and sensitive “turn-on” fluorescent chemosensor for mercury(II) ion in water and its application for cell imaging

Abstract

The existence of extremely toxic mercury contaminants in the environment, even at very low concentrations, poses severe human health issues. Mercury exposure may lead to various diseases, such as prenatal brain damage, cognitive severe, motion disorders, and Minamata diseases. Hence, developing an effective and selective method to detect Hg²⁺ in the environment and biological samples is of great interest. Amongst various Hg²⁺ detection techniques, fluorescent chemosensors offer more convenient procedures, affordable cost, high selectivity, and the capability to perform cell imaging for Hg²⁺ detection. Herein, a novel "turn-on" fluorescent chemosensor, Thiourea-DHP derivative (TUD), highly selective to Hg²⁺, was successfully developed. TUD was synthesized by cyclotrimerization of β-amino acrylate, followed by the thioacylation of the resulting dihydropyridine (DHP) with dimethylamino thiocarbonyl chloride. The Hg²⁺ detection by TUD displayed an astonishing naked-eye blue fluorescence signal under blacklight, exhibiting an LOD of 69 nM or 14 ppb at pH 7.4 in the HEPES buffer. Hg²⁺-induced hydrolytic desulfurization of the low fluorescent TUD to produce the strongly fluorescent urea-DHP (UD) is proposed as a mechanism for this fluorescence enhancement. The formation of UD was confirmed by ¹H NMR, ¹³C NMR, and HRMS. This detecting system of TUD provided excellent percentage recovery (>97 %) for the analysis of Hg²⁺ contaminants in real-environmental water samples. Besides, the TUD probe showed nontoxic properties in living cells towards RAW264.7 murine macrophage cell line even at high concentrations (100 µM). Our proposed TUD probe demonstrated superior sensitivity in pure aqueous media compared to current mercury-desulfurization fluorescent chemosensors. This sensing system proved effective for analysing Hg²⁺ contaminants in real-environmental water samples. Additionally, the nontoxic TUD probe successfully revealed the remarkable biocompatibility for Hg²⁺ detection in living cells.