Synthesis and aggregation-induced emission properties of pyridine and pyridinium analogues of tetraphenylethylene

Abstract

Tetraphenylethylenes in which one or two of the core phenyl rings have been replaced with pyridine or pyridinium groups have been prepared and evaluated as aggregation-induced emission fluorophores.

Synthesis and Evaluation of Tetraarylethylene-based Mono-, Bis-, and Tris(pyridinium) Derivatives for Image-Guided Mitochondria-Specific Targeting and Cytotoxicity of Metastatic Melanoma Cells

“…The synthesis of triphenylvinylpyridine (TPVP, 1 ) was accomplished by a Peterson olefination reaction between the lithiated anion of silylated diphenylmethane and 4-pyridyl phenyl ketone as recently reported [22]. The corresponding pyridinium salt 2 was easily obtained in good yield upon refluxing 1 with 1-bromodecane.…”

“…Mitochondrial localization of these agents produced cytotoxic effects in melanoma cells, which correlated with disruption of oxidative phosphorylation, and increases in cellular O 2 •− /H 2 O 2 levels. he lipophilic tetraarylethylene-based vinylpyridinium salts utilized in this study also display fluorescence emission in aqueous solution and in vitro , and belong to a class of aggregation-induced emission (AIE) compounds [22–26]. AIE-active compounds differ from conventional fluorophores in that their fluorescence at low concentrations becomes enhanced in the aggregated state ( e.g., when embedded in cell membranes) [23–26].…”

“…AIE-active compounds differ from conventional fluorophores in that their fluorescence at low concentrations becomes enhanced in the aggregated state ( e.g., when embedded in cell membranes) [23–26]. This fluorescence phenomenon is attributed to inhibition of aryl–ethylene bond rotations, and differentiates tetraarylethylene-based vinylpyridinium derivatives from traditional mitochondrial targeted compounds [22, 27–29]. For example, triphenylphosphonium (TPP) compounds have been used for decades as a lipophilic-cationic delivery vehicle for targeting mitochondria.…”

“…However, imaging of TPP-based delivery to mitochondria requires the addition of bulky fluorescent groups [27–30]. In addition, tetraarylethylene vinylpyridinium derivatives are distinguished from traditional fluorescent and mitochondrial targeting compounds by displaying substantial synthetic flexibility and maintaining the potential for improved hydrophilicity (by increasing the number of pyridine substitutions) [22, 27–29]. Currently, few heteroaromatic tetraarylethylenes have been reported, and the biochemical properties and therapeutic potential of these compounds have not been examined [22].…”

Mitochondrial-Targeted Decyl-Triphenylphosphonium Enhances 2-Deoxy-D-Glucose Mediated Oxidative Stress and Clonogenic Killing of Multiple Myeloma Cells

“…Based on mitochondrial alterations in MM stem like cells (increase mitochondrial number, Δψ m , and orthodox:condensed mitochondria ratios) we hypothesized that 10-TPP treatment can potentially increase oxidative stress and cytotoxicity of MM stem-like cells. For mitochondrial imaging, we used an aggregation-induced emission active triphenylvinylpyridine (TPVP) agent with 10-carbon chain (10-TPVP, C 35 H 40 BrN, 554.6) [53, 113]. Our results suggest that 10-TPP can potentially localize to mitochondria and increases cellular pro-oxidant levels as well as mitochondrial O 2 •− level in MM cells.…”