Characterization of Acridancarboxylic Acid Derivatives as Chemiluminescent Peroxidase Substrates

• Published in: Journal of organic chemistry Vol. 63; no. 4; pp. 930 - 937
• Main Authors: Akhavan-Tafti, Hashem, DeSilva, Renuka, Arghavani, Zahra, Eickholt, Robert A, Handley, Richard S, Schoenfelner, Barry A, Sugioka, Katsuaki, Sugioka, Yumiko, Schaap, A. Paul
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.02.1998; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ESTER; HYDROLYSIS; IMMUNOASSAY; KINETICS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo970202m

A new class of peroxidase substrates has been developed which produces chemiluminescence upon enzymatic oxidation. A wide variety of N-alkylacridancarboxylic acid derivatives including esters, thioesters, and sulfonamides are efficiently oxidized by a peroxidase and a peroxide to enzymatically produce the corresponding chemiluminescent acridinium compound. In conjunction with a peroxidase enhancer, continuous light emission with high light intensities and an extended duration are produced. Alternately, an appropriately designed acridan substrate produces a stable acridinium ester intermediate which can be accumulated and the chemiluminescence elicited as a burst of light by raising the pH. The effects of leaving groups and substitution on the acridan ring on the mechanism of light production are discussed. Peroxidase-catalyzed oxidation in the presence of a peroxide permits the detection of enzyme with subattomolar sensitivity and a broad linear dynamic range.