Synthesis and Chemiluminescent Properties of Amino-Acylated luminol Derivatives Bearing Phosphonium Cations

Abstract

The monitoring of reactive oxygen species in living cells provides valuable information on cell function and performance. Lately, the development of chemiluminescence-based reactive oxygen species monitoring has gained increased attention due to the advantages posed by chemiluminescence, including its rapid measurement and high sensitivity. In this respect, specific organelle-targeting trackers with strong chemiluminescence performance are of high importance. We herein report the synthesis and chemiluminescence properties of eight novel phosphonium-functionalized amino-acylated luminol and isoluminol derivatives, designed as mitochondriotropic chemiluminescence reactive oxygen species trackers. Three different phosphonium cationic moieties were employed (phenyl, p-tolyl, and cyclohexyl), as well as two alkanoyl chains (hexanoyl and undecanoyl) as bridges/linkers. Synthesis is accomplished via the acylation of the corresponding phthalimides, as phthalhydrazide precursors, followed by hydrazinolysis. This method was chosen because the direct acylation of (iso)luminol was discouraging. The new derivatives’ chemiluminescence was evaluated and compared with that of the parent molecules. A relatively poor chemiluminescence performance was observed for all derivatives, with the isoluminol-based ones being the poorest. This result is mainly attributed to the low yield of the fluorescence species formation during the chemiluminescence oxidation reaction.

Modulation by Phosphonium Ions of the Activity of Mitotropic Agents Based on the Chemiluminescence of Luminols

“…These anhydrides were found to hydrolyze in basic aqueous m the corresponding phthalates 1a-c, so they were used as their in situ precu ure S1 in the Supplementary Materials). In the framework of our research towards mitotropic, highly efficient, luminol-based, CL ROS detectors, consisting of covalently attached TPPCs onto luminol via a linker [24], the photophysical interaction between the light-emitting species 3AP * and TPPC needs to be evaluated as it can add valuable information on the design of novel emission-based mitotropic systems. To the best of our knowledge, the photophysical evaluation of TPPCs as aminophthalate quenchers is presented here for the first time.…”

“…4-Amino-2-(sec-butyl)isoindoline-1,3-dione 2 was synthesized as previously published [24]. All derivatives were characterized by 1 H and 13 C-NMR and ESI-HRMS.…”

Building a Functionalizable, Potent Chemiluminescent Agent: A Rational Design Study on 6,8-Substituted Luminol Derivatives

“…We thus opted for an alternative, modular, and reproducible synthetic strategy. 3-Aminophthalimide 3, prepared easily from 3-aminophthalic acid, 14 was used as the starting material. Bromination, using excess of bromine or NBS, afforded the 4,6-dibrominated derivative 4 in high yield (Scheme 2).…”

Modulation by Phosphonium Ions of the Activity of Mitotropic Agents Based on the Chemiluminescence of Luminols

“…4-Amino-2-(sec-butyl)isoindoline-1,3-dione 2 was synthesized as previously published. 23 4-Amino-5,7-dibromo-2-( sec -butyl)isoindoline-1,3-dione (3). A round-bottom ask was charged with aminophthalimide 2 (1 g, 4.6 mmol) and sodium acetate (762 mg, 9.3 mmol) in acetic acid (11 mL) and the resulting solution was stirred at r.t. for 30 mins.…”

“…In the framework of our research towards mitotropic, highly e cient, luminol-based, CL ROS detectors, consisting of covalently attached TPPCs onto luminol via a linker, 23 the photophysical interaction between the light emitting species 3AP* and TPPC needs to be evaluated as it can add valuable information on the design of novel emission-based mitotropic systems. To the best of our knowledge, the photophysical evaluation of TPPCs as aminophthalate quenchers is presented here for the rst time.…”