Synthesis and properties of chemiluminescent acridinium ester labels with fluorous tags

Abstract

Acridinium dimethylphenyl esters are highly sensitive chemiluminescent labels that are used in clinical diagnostics. Light emission from these labels is triggered with alkaline peroxide in the presence of the cationic surfactant cetyltrimethylammonium chloride (CTAC). CTAC compresses emission times of these labels to <5 seconds and also increases overall light yield 3-4 fold. The observed enhancement in acridinium ester chemiluminescence (light yield) is quite sensitive to the polarity of the micellar interface. In the current study, we report the synthesis of new acridinium ester labels with fluorous tags of varying fluorine content and their chemiluminescence in the presence of cationic micelles of CTAC, anionic micelles of sodium perfluorooctanoate (SPFO) as well as mixed micelles of CTAC and SPFO. These studies indicate that in the presence of the mixed micelle system of CTAC and SPFO and at low mole fractions of SPFO, polarity of the mixed micelle interface is lower than that of CTAC leading to a greater enhancement of chemiluminescence for both fluorinated acridinium esters as well as a structurally analogous but non-fluorinated acridinium ester. Chemiluminescence stability of the fluorinated acridinium esters was either comparable to or better than the stability of the non-fluorinated acridinium ester. Non-specific binding to paramagnetic microparticles was higher for fluorinated acridinium esters requiring a surfactant wash to reduce their non-specific binding to the same extent as that observed for the non-fluorinated acridinium ester.

A green synthesis of chemiluminescent N-sulfopropyl acridinium esters in ionic liquids without using the carcinogen 1,3-propane sultone

“…The reduction reaction proceeded cleanly and very rapidly as evidenced by the bleaching of the yellow-colored solution of the protonated acridine ester almost instantaneously upon the addition of the reducing agent. The loss of color results from disruption of the acridinium ring chromophore [3] by hydride reaction at C-9 in a 1,4-addition reaction that is facilitated by the positive charge on the protonated acridine nitrogen. Because sodium cyanoborohydride is generally considered to be toxic due to potential for hydrogen cyanide formation, we investigated alternate methods of reduction including catalytic hydrogenation as well as other less-toxic reducing agents such as sodium tri(acetoxy) borohydride [31], sodium borohydride, and picoline-borane [32].…”

Firefly-Inspired Approach to Develop New Chemiluminescence Materials

“…One important method to develop a new class of chemiluminescent materials is the simulation of bioluminescent ED reactions. For example, enol forms of acridinium esters oxidized by hydrogen peroxide have been used in analytical applications (Natrajan et al., 2014). Herein, we present a novel series of artificial chemiluminescent materials inspired by the amazing ED reaction of natural bioluminescent molecules.…”

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.…”

“…Various representative chemiluminescent compounds such as luminol, [1][2][3][4] indole, [5,6] acridinium ester [7][8][9][10] and lophine derivatives [11,12] were developed and the chemiluminescence (CL) properties of each were studied. However, these representative chemiluminescent compounds require strongly alkaline conditions to obtain strong CL intensity.…”

“…[15] Second, cetyltrimethylammonium chloride, cationic surfactant, increased CL intensity of various acridinium esters under alkaline conditions. [16][17][18] 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. Moreover, the enhancement effect by cetyltrimethylammonium bromide (CTAB) on CL of them was investigated.…”