Chemiluminescence 1,2-dioxetanes, substituted

In the past few years two rather distinct classes of chemiluminescent dioxetanes have become evident. Alkyl, alkoxy, and simple aryl substituted dioxetanes, which includes the earliest dioxetanes prepared, are characterized... 

Bronstein I, Brooks E, Rouh-Rong J, inventors (1994) Chemiluminescent 3-(substituted adamant-2 -ylidene) 1,2-dioxetanes. United States patent 5,326,882... 

Hoshiya N, Fukuda N, Maeda H, Watanabe N, Matsumoto M. Synthesis and fluoride-induced chemiluminescent decomposition of bicyclic dioxetanes substituted with a 2-hydroxynaphthyl group. Tetrahedron 2006 62 5808-20. 

In 1982, the Schaap group demonstrated that chemiluminescence can be induced by the addition of a base to dioxetanes bearing a phenolic substituent [11]. Herein, the same group presents a method utilizing aryl esterase to catalyze the cleavage of a naphthyl acetate-substituted dioxetane in aqueous buffer at ambient... 

Me Capra in particular proposed n> that the chemiluminescence reactions of a large number of organic compounds had this concerted dioxetane decomposition step as key reaction in the production of electronically excited products, namely acridinium salts 25,26,27) indolylperoxides 28>, activated oxalic esters 29>, diphenyl carbene 30>, tetrakis-dimethylamino-ethylene 31 32>, lucigenin 33>, and substituted imidazoles 23>. 

CIEEL is of particular interest for the development of modern chemiluminescent bioassays. The most popular clinical bioassays utilize thermally persistent spiro-adamantyl-substituted dioxetanes with a protected phenolate moiety. These designed 1,2-dioxetanes include an energy source, a fluorophore, and a trigger grouping, and are therefore structurally similar to bioluminescent substrates such as firefly luciferin. Three main commercial dioxetanes 75 are available as one-reagent assays for alkaline phosphatase and are sold under the name of AMPPD (R1 = R2 = H), CSPD (R1 = Cl, R2 = H), and CDP-Star (R1 = R2 = Cl) <2006S1781, 2003ANA279>. These substrates are sensitive to 10 21 mol of alkaline phosphatase in solution. 

In fact, the chemiluminescence of an authenic sample of trans- 3,4-diphenyl-1,2-dioxetane, prepared by Kopecky s procedure [118] and then added to the DCA-sensitized reaction on traws-stilbene (E° = 1.51 V vs SCE), totally disappears within a few minutes [119]. In spite of this elegant demonstration, the intermediacy of these short-lived compounds required further direct evidence. In this regard, although different mechanistic pathways can account for the reaction products [34,120,121], Schaap et al. [98] isolated in the DCA-sensitized photooxygenations of adamantylidene-adamantane (E° = 1.46 V vs SCE) 21 and/or of several substituted 2,3-diphenyl-5,6-dihydro-l,4-dioxins (Eox in the range 0.72-1.07 V vs SCE) 22a-f the correspopnding stable 1,2-dioxetanes 23, 24a-f [Eqs. (10,11)] in good yields. 

The fact that hyperenergetic molecules such as the 1,2-dioxetanes should be prone by catalytic decomposition is not surprising. Early examples include the protecting effect of molecular oxygen on the thermal decomposition of 3,4-diethoxydioxetane, the efficient catalytic decomposition of this dioxetane by amines, and of alkyl-substituted dioxetanes by transition-metal ion impurities. However, all of these catalytic decompositions are competing dark reactions that greatly diminish the chemiluminescence efficiency of the dioxetanes. 

Some substituted alkenes react with singlet oxygen to form a dioxetane in a -f- cycloaddition reaction. Most dioxetanes readily decompose to carbonyl compounds in an exothermic reaction that is accompanied by a bluish luminescence. The chemiluminescence will be dealt with in more detail in Section 7.6.4. 

Dioxetane substrates for alkaline phosphatase and p-galac-tosidase The four-membered ring peroxides, 1,2-dioxetanes, are too unstable to be used as chemiluminescent substrates due to their low energy of activation (Adam and Cilento, 1983). Substitution of the carbonyls in the dioxetane ring has substantial effects on the rate of decomposition (Wieringa et al., 1972), i.e., half-lives from less than a second for simple dioxetanes to over 21 years for some of the... 

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