3-Hydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one and 3-hydroxy-6H-benzo[c] chromen-6-one act as on-off selective fluorescent sensors for Iron (III) under in vitro and ex vivo conditions

Abstract

Regarding the abundant use of metals for different purposes, it becomes more critical from various scientific and technological perspectives to discover novel agents as selective probes for the detection of specific metals. In our previous studies, we have shown that aqueous solutions of natural urolithins (i.e., hydroxyl-substituted benzo[c]chromen-6-one derivatives) are selective Iron (III) sensors in fluorescence assays. In this study, we have extrapolated these findings to another coumarine compound (i.e., 3-Hydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one) and compared the selective metal binding properties with Urolithin B (i.e., 3-Hydroxy-6Hbenzo[c]chromen-6-one). Following the synthesis and structure identification studies, the fluorometric studies pointed out that the lactam group in the structure still persists to be the important scaffold for maintaining selective ON-OFF sensor capacity that renders the compound a selective Iron (III) binding probe. Moreover, for the first time, fluorescence cellular imaging studies concomitant to cytotoxicity assays with the title compounds were also performed and the results displayed the cell-penetrative, safe, and fluorescent detectable characteristics of the compounds in neuroblastoma and glioblastoma cells through servings as intracellular Iron (III) on-off sensors.

The investigation of fluorescence and metal interaction properties of racemic 7,8,9,10-tetrahydro-3-hydroxy-4-(1-hydroxyethyl)benzo[c]chromen-6-one

“…The fluorescence scanning of THU-4-OH was found identical with our previous measurements [ 20 ]. The UV spectrum of THU-4-Ac has revealed out 320 nm as the wavelength for the maximum absorption.…”

“…Briefly, 0.22 g resorcinol, 0.37 g ethyl 2-oxo-cyclohexancarboxylate, and 0.4 g ZrCl 4 were mixed in a 20 mL reaction flask and heated at 85 °C for 1 h. The precipitate formed was filtered off and washed with ice-cold water. The spectral analysis of the compound was found identical with our previous findings [ 20 – 21 ].…”

“…The synthetic scheme is provided in Figure 1 for the title compounds. THU-OH was obtained according to the protocol previously published [ 20 ]. The 4-acetyl and 4-(1-hydroxyethy) derivatives of THU-OH were obtained in good yields.…”

“…THU-OH was synthesized according to the previously published methodology [ 20 – 21 ]. Briefly, 0.22 g resorcinol, 0.37 g ethyl 2-oxo-cyclohexancarboxylate, and 0.4 g ZrCl 4 were mixed in a 20 mL reaction flask and heated at 85 °C for 1 h. The precipitate formed was filtered off and washed with ice-cold water.…”

“…also referred to as Urolithin B) and discovered its on-off fluorescence probe property in the presence of iron (III) [ 18 ]. In the continuation of this work, the alternative hydroxyl substituted, methyl ether derivatives, and 7,8,9,10-tetrahydro-3-hydroxybenzo[c]chromen-6-one, the partial saturated form of Urolithin A, were synthesized, and it was observed that all these compounds, similar to Urolithin A, possess on-off fluorescent sensor character selective towards iron (III) [ 19 – 20 ]. All these alternative substitution patterns and the constant iron (III) sensor on-off character of the derivatives considered pointed out the significance of the lactone group in the interaction.…”