A pH-Sensitive Fluorescent Chemosensor Turn-On Based in a Salen Iron (III) Complex: Synthesis, Photophysical Properties, and Live-Cell Imaging Application

Abstract

pH regulation is essential to allow normal cell function, and their imbalance is associated with different pathologic situations, including cancer. In this study, we present the synthesis of 2-(((2-aminoethyl)imino)methyl)phenol (HL1) and the iron (III) complex (Fe(L1)2Br, (C1)), confirmed by X-ray diffraction analysis. The absorption and emission properties of complex C1 were assessed in the presence and absence of different physiologically relevant analytes, finding a fluorescent turn-on when OH− was added. So, we determined the limit of detection (LOD = 3.97 × 10−9 M), stoichiometry (1:1), and association constant (Kas = 5.86 × 103 M−1). Using DFT calculations, we proposed a spontaneous decomposition mechanism for C1. After characterization, complex C1 was evaluated as an intracellular pH chemosensor on the human primary gastric adenocarcinoma (AGS) and non-tumoral gastric epithelia (GES-1) cell lines, finding fluorescent signal activation in the latter when compared to AGS cells due to the lower intracellular pH of AGS cells caused by the increased metabolic rate. However, when complex C1 was used on metastatic cancer cell lines (MKN-45 and MKN-74), a fluorescent turn-on was observed in both cell lines because the intracellular lactate amount increased. Our results could provide insights about the application of complex C1 as a metabolic probe to be used in cancer cell imaging.

“Covalent‐Disassembly”‐Based Approaches For Sensing Applications

“…[75,77] Recently, an octahedral Fe(III) complex 18 with two tridentate 2-(((2-aminoethyl)imino)methyl)phenol ligands was introduced for the fluorescent staining of gastric cancer (MKN-45, MKN-74) and non-tumoral (GES-1) cell lines. [32] The DMSO-soluble complex shows solvatochromic behaviour and disassembles under basic conditions with the release of fluorescent salicylaldehyde 2. Its robustness toward coordinating analytes is explained by the lack of a free coordination site and the intracellular disassembly process is most likely initiated by deprotonation of a coordinated amine donor functionality by hydroxide.…”

“…Its robustness toward coordinating analytes is explained by the lack of a free coordination site and the intracellular disassembly process is most likely initiated by deprotonation of a coordinated amine donor functionality by hydroxide. [32] Figure 11. Left: A-D: DB-Cu(II)-probes 13-16 for detecting AA.…”

“…[20][21][22][23][24][25][26] Other examples of metal-imine containing DBprobes describe the selective detection of cyanide ions (CN À ), gasotransmitter H 2 S, L-homocysteine (L-HCy), L-cysteine (L-Cys) and changes in pH, both in vitro and cancer cells. [27][28][29][30][31][32]…”