Effective chemiluminogenic systems based on acridinium esters bearing substituents of various electronic and steric properties

Abstract

A series of 10-methyl-9-(phenoxycarbonyl)acridinium trifluoromethanesulfonates (XAEs), bearing substituents of various characteristics in the lateral benzene ring (2-halogen, 2,6-dihalogen, 2-trifluoromethyl, 2-nitro, 2-methoxy, 3-halogen and 4-halogen) were synthesized with high yields, identified and subjected to a physicochemical and theoretical investigation. The main task of the work was to assess the mechanism and optimal conditions of light emission in various liquid systems based on the above salts in order to evaluate their potential usefulness as chemiluminescence (CL) labels and indicators in ultra-sensitive analyses. Density functional theory (DFT) calculations were performed to investigate the detailed mechanism of the oxidation of 9-substituted 10-methylacridinium cations involved in XAEs by hydrogen peroxide in alkaline media. Three general pathways were drawn, which are termed the "light path" (chemiluminogenic) and there were two "dark paths" (non-chemiluminogenic): hydrolytic and "pseudobase". The CL time profiles, triggered in alkaline solutions containing hydrogen peroxide, enabled us to establish crucial physicochemical parameters, including pseudo-first order kinetic constants of CL decay and relative efficiencies of emission. In order to optimize the systems' luminogenic performance, different bases, such as sodium hydroxide, tetrabutylammonium hydroxide (TBAOH) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), as well as enhancers, such as cationic, zwitterionic and neutral surfactants (cetyltrimethylammonium chloride (CTAC), N,N-dimethyldodecylammonio-1,3-propane sulfonate (DDAPS) and Triton X-100, respectively) were tested. The results revealed the optimal CL systems, which enabled us to obtain substantially higher emissions than typical ones, based on acridinium esters or luminol. The derived parameters, characterizing the potential utility of the acridinium esters, such as stability in aqueous environments and usefulness (the product of emission efficiency and stability at a given pH), enabled us to reveal the best candidates and their practical applications. The post-reaction mixtures, analyzed by means of chromatography (RP-HPLC) and mass spectrometry (ESI-MS), allowed us to verify the occurrence and population of the products that were theoretically predicted, i.e. 10-methyl-9-acridinone (NMAON), 10-methylacridinium-9-carboxylic acid (NMACA) and substituted phenols (RPhOHs).

On the use of acridinium indicators for the chemiluminescent determination of the total antioxidant capacity of dietary supplements

“…Acridinium salts, particularly aromatic esters of acridine 9‐carboxylic acid (AEs), are more advanced chemiluminogenic substrates, gaining an increasing significance in modern trace analytics. They demonstrate a few beneficial physicochemical properties, such as a relatively high emission efficiency in aqueous environments (up to twice that of luminol) and flash‐type kinetics – which, in addition, can be easily manipulated by modifying the aryloxy leaving group . King et al have successfully used a flow‐injection analysis to assess the content of the oxidizer hydrogen peroxide in natural waters.…”

“…The presented luminometric method relies on the ability of some acridinium cations – in particular the aromatic esters of 10‐methylacridinium‐9‐carboxylic acid – to undergo an effective oxidation under the action of hydrogen peroxide/sodium hydroxide system, resulting in the formation of electronically excited molecules of a highly florescent product, namely 10‐methylated acridan‐9‐one . The original CL indicators employed have been selected to provide moderate emission decay kinetics and possibly high emission efficiency under assay conditions.…”

“…The original CL indicators employed have been selected to provide moderate emission decay kinetics and possibly high emission efficiency under assay conditions. We have made selections based on our earlier research on the physicochemistry of chemiluminogenic systems basing on acridinium salts …”

“…The developed analytical format exhibits significant advantages in comparison with the assays based on the luminol, i.e. a high quantum yield of temporary emission intensity, relatively broad linear range and good sensitivity to environmental changes …”

Enhancement effect on the chemiluminescence of acridinium esters under neutral conditions

“…This phenoxy radical may be important for the enhancement effect on luminol CL . Second, cetyltrimethylammonium chloride, cationic surfactant, increased CL intensity of various acridinium esters under alkaline conditions . Thus, the enhancement effect by phenol compounds on CL of phenyl 10‐methyl‐10λ 4 ‐acridine‐9‐carboxylate derivatives with electron‐withdrawing groups at the 4‐position of the phenyl group was evaluated in the presence and absence of horseradish peroxidase.…”