Substitution 1,2-dioxetane chemiluminescence

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... 

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 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... 

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. 

More than twenty years ago, Schaap et al discovered chemiluminescence from phenoxide substituted dioxetanes (PHOD) as a model for firefly bioluminescence. McCapra had suggested a charge or an electron transfer is involved for such process, but confirmative evidences had not been presented at that time. Recently successive synthetic efforts on phenoxide.substituted dioxetanes produced a series of efficient chemiluminescent molecules. ... 

Schaap AP, Chen TS, Handley RS, DeSilva R, Giri BP. Chemical and enzymatic triggering of 1,2-dioxetanes. 2 Fluoride-induced chemiluminescence from tert-butyl dimethylsililoxy-substituted dioxetanes. Tetrahedron Lett 1987 28 1155-8. 

In conclusion, we have discovered that chelation with alkaline metal ion, especially Li+, enhances markedly chemiluminescence efficiency of CTICL for an even pattern hydroxyaryl-substituted dioxetane, i.e., bicyclic dioxetane bearing a 3-hydroxynaphthalene-2-yl group 1 in THF. 

Fig. 3. Generation of chemiluminescence by thermal decomposition of substituted dioxetanes.

Schaap, A. P., Handley, R. S., and Giri, B. P., Chemical and enzymatic triggering of 1,2-dioxetanes 1 Aryl esterase-catalyzed chemiluminescence from a naphthyl acetate-substituted dioxetane. Tetrahedron Lett. 28, 935-938 (1987). 

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>. 

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. 

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