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

Abstract

Chemiluminescent acridinium dimethylphenyl esters containing hydrophilic N-sulfopropyl groups in the acridinium ring are used as labels in automated immunoassays for clinical diagnostics. Introduction of the N-sulfopropyl group in these labels is normally accomplished by N-alkylation of the corresponding, nonchemiluminescent acridine ester precursors with the toxic carcinogen 1,3-propane sultone. In the current study, we report that sodium 3-bromopropane sulfonate in ionic liquids (ILs) is a benign alternative to 1,3-propane sultone for introducing the N-sulfopropyl group in chemiluminescent acridinium ester labels. The sultone reagent can be eliminated in the synthesis of N-sulfopropyl acridinium dimethylphenyl ester labels by taking advantage of the increased reactivity of acridan esters toward nontoxic sodium 3-bromopropane sulfonate in [BMIM][BF₄]. Sodium 3-bromopropane sulfonate in ILs is also potentially a nontoxic alternative to 1,3-propane sultone for introducing the water-soluble, three-carbon sulfobetaine moiety in other molecules as well.

Keywords:

• green synthesis
• chemiluminescent N-sulfopropyl acridinium ester
• ionic liquid
• acridan N-alkylation
• sodium 3-bromopropane sulfonate