Dioxetane chemiluminescence efficiency

Recently, the synthesis has been reported of the novel bicyclic dioxetanes 22a-c , which possess a remarkable chemiluminescence efficiency in aqueous media. Of the dioxetanes 22a-c with the 3-hydroxy-4-isoxazolylphenyl functionality, the derivative 22a is the most suitable On triggering by NaOH in water, the dioxetane 22a displays the highest CIEEL yield (0.24 at 25 °C), whereas the efficiency of componnds 22b and 22c is much lower (0.064 and 0.015, respectively). Nevertheless, the latter are still snfficiently efficient triggerable dioxetanes and quite adequate for their use in aqneons media. Snch unprecedented results definitely merit further exploration. 

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. 

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. 

This was further elaborated upon by Schuster and co-workers (K21, S23, S24) and by Schaap s group at Wayne State University (S6, S8, SIO, Sll, Z2, Z3). Thus, the observation that some hydroxy-substituted aromatic dioxetanes show high chemiluminescent efficiencies at alkaline pH (phenolic anionic form) led to the formulation of a third mechanism for chemiluminescent decomposition of dioxetanes. This mechanism, known initially as intramolecular electron transfer (Ml9, Z2) and subsequently as chemically initiated electron exchange luminescence, or CIEEL (FI, K20), can be best illustrated by reference to the dioxetane shown in Fig. 37, where the chemiluminescence is triggered by the addition of fluoride ions. 

Schaap, A. P., DeSilva, R., Akhavan-Tafti, H., and Handley, R. S., Chemical and enzymatic triggering of dioxetanes Structural effects on chemiluminescence efficiency. In Bioluminescence and Chemiluminescence Current Status (P. E. Stanley and L. J. Kricka, eds.), pp. 103-106. Wiley, Chichester, 1991. 

The activation energy in this case varied from 87 to 93 kJ/mol in different solvents. From the temperature dependence, several competitive reaction paths for this dimethyl-dioxetanone decomposition were deduced, all having a biradical as first intermediate. Heavy-atom effects often play a role in dioxetan chemiluminescence. If DBA is used as fluorescer, the quantum yield is markedly greater than that observed when DPA is used - although the latter has a fluorescence efficiency of 0.89, compared with 0.1 for DBA. In both cases triplet-singlet energy transfer is the origin of the chemiluminescence. 

The first detailed investigation of the reaction kinetics was reported in 1984 (68). The reaction of bis(pentachlorophenyl) oxalate [1173-75-7] (PCPO) and hydrogen peroxide cataly2ed by sodium saUcylate in chlorobenzene produced chemiluminescence from diphenylamine (DPA) as a simple time—intensity profile from which a chemiluminescence decay rate constant could be determined. These studies demonstrated a first-order dependence for both PCPO and hydrogen peroxide and a zero-order dependence on the fluorescer in accord with an earher study (9). Furthermore, the chemiluminescence quantum efficiencies Qc) are dependent on the ease of oxidation of the fluorescer, an unstable, short-hved intermediate (r = 0.5 /is) serves as the chemical activator, and such a short-hved species "is not consistent with attempts to identify a relatively stable dioxetane as the intermediate" (68). 

Second, whereas the cleavage barrier for the dioxetane is reduced on electron transfer (Figure la), for the a-peroxy lactone it disappears completely (Figure lb) presumably, the 0—0 bond is irreversibly cleaved for the a-peroxy-lactone radical anion . This finding is consistent with the experimental observation that the a-peroxy lactones are considerably more efficient in the electron-transfer-induced chemiluminescence than the corresponding dioxetanes . Thus, if persistent a-peroxy lactones were readily accessible, they should be reagents of choice for commercial applications of chemiluminescence. 

The rational design of effective and efficient dioxetane-based bioanalytical probes requires the in-depth mechanistic understanding of the enzymatically triggered chemiluminescence. In this context, alkaline-phosphatase-triggered CIEEL furnishes a textbook example , which will be examined below in detail. 

Like other peroxides, also dioxetanes are sensitive to the presence of metal ions and their complexes, which catalyze the decomposition of the dioxetane molecule. In most cases, this decomposition is dark, i.e. no chemiluminesce is generated in such a catalytic cleavage42. An informative exception, for instance, constitutes the chemiluminescent decomposition of the dioxetane 19 in Scheme 13, initiated by the ruthenium complex Ru(bipy)3Cl243. It has been shown that this chemiexcitation derives from the valence change of the ruthenium ion in the process Ru3+ I e — Ru2+, for which the efficiency of the excited-state generation may be as much as 40%44. Hence, when the radical anion of the carbonyl cleavage fragment from the dioxetane and the Ru3+ ion are formed in... 

Undoubtedly, the most characteristic property of 1,2-dioxetanes and a-peroxylactones is the fact that they emit light on thermal decomposition. Since in liquid media in the presence of molecular oxygen triplet excited states are efficiently quenched, the observed direct chemiluminescence is ascribed to the fluorescence of the carbonyl product. This fluorescence occurs usually at 420 10nm and corresponds to n n excitation.The shortest wavelength emission has probably been observed for the indole-1,2-dioxetane (17) that occurs at 320 nm. ... 

The kinetics of the thermal decomposition of 1,2-dioxetanes and a-peroxylactones are first order and are usually unimolecular. A variety of experimental methods can be used to monitor the rates. These include direct chemiluminescence of the excited carbonyl product,energy-transfer chemiluminescence of the chemienergized excited carbonyl product to an efficient fluorescer, dioxetane consumption or carbonyl product formation by nmr spectroscopy iodometry of the cyclic... 

Trapping experiments would constitute the most unequivocal proof for the intervention of diradical intermediates in the decomposition of 1,2-dioxetanes. Although such experiments have not been reported to date, the interesting observation that tri-Z-butylphenol extinguished the trimethyldioxetane chemiluminescence more efficiently than piperylene, was construed as evidence that the phenol scavenged a relatively long-lived precursor, presumably a diradical to the electronically excited product. ... 

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