Dioxetanones decomposition mechanisms

One is the concerted decomposition of a dioxetanone structure that is proposed for the chemiluminescence and bioluminescence of both firefly luciferin (Hopkins et al., 1967 McCapra et al., 1968 Shimomura et al., 1977) and Cypridina luciferin (McCapra and Chang, 1967 Shimomura and Johnson, 1971). The other is the linear decomposition mechanism that has been proposed for the bioluminescence reaction of fireflies by DeLuca and Dempsey (1970), but not substantiated. In the case of the Oplopborus bioluminescence, investigation of the reaction pathway by 180-labeling experiments has shown that one O atom of the product CO2 derives from molecular oxygen, indicating that the dioxetanone pathway takes place in this bioluminescence system as well (Shimomura et al., 1978). It appears that the involvement of a dioxetane intermediate is quite widespread in bioluminescence. 

An apparently bimolecular decomposition mechanism is observed in the presence of fluorescent aromatic hydrocarbons. Rubrene was the first catalyst used [25], considerably enhancing the chemiluminescence of the a-peroxy lactones. Triplet-triplet annihilation of rubrene triplets was suggested, these being produced by energy transfer from the dioxetanone decomposition products. However, this suggestion was not corroborated by further experimental evidence. 

Subsequent studies (63,64) suggested that the nature of the chemical activation process was a one-electron oxidation of the fluorescer by (27) followed by decomposition of the dioxetanedione radical anion to a carbon dioxide radical anion. Back electron transfer to the radical cation of the fluorescer produced the excited state which emitted the luminescence characteristic of the fluorescent state of the emitter. The chemical activation mechanism was patterned after the CIEEL mechanism proposed for dioxetanones and dioxetanes discussed earher (65). Additional support for the CIEEL mechanism, was furnished by demonstration (66) that a linear correlation existed between the singlet excitation energy of the fluorescer and the chemiluminescence intensity which had been shown earher with dimethyl dioxetanone (67). 

Fig. 1.12 Mechanism of the bioluminescence reaction of firefly luciferin catalyzed by firefly luciferase. Luciferin is probably in the dianion form when bound to luciferase. Luciferase-bound luciferin is converted into an adenylate in the presence of ATP and Mg2+, splitting off pyrophosphate (PP). The adenylate is oxygenated in the presence of oxygen (air) forming a peroxide intermediate A, which forms a dioxetanone intermediate B by splitting off AMP. The decomposition of intermediate B produces the excited state of oxyluciferin monoanion (Cl) or dianion (C2). When the energy levels of the excited states fall to the ground states, Cl and C2 emit red light (Amax 615 nm) and yellow-green light (Amax 560 nm), respectively.

Fig. 3.3.4 Reaction mechanism of the coelenterazine bioluminescence showing two possible routes of peroxide decomposition, the dioxetanone pathway (upper route) and linear decomposition pathway (lower route). The Oplopborus bioluminescence takes place via the dioxetanone pathway. The light emitter is considered to be the amide-anion of coelenteramide (see Section 5.4).

The decomposition of dioxetanone may involve the chemically initiated electron-exchange luminescence (CIEEL) mechanism (McCapra, 1977 Koo et al., 1978). In the CIEEL mechanism, the singlet excited state amide anion is formed upon charge annihilation of the two radical species that are produced by the decomposition of dioxetanone. According to McCapra (1997), however, the mechanism has various shortfalls if it is applied to bioluminescence reactions. It should also be pointed out that the amide anion of coelenteramide can take various resonance structures involving the N-C-N-C-O linkage, even if it is not specifically mentioned. 

The CIEEL mechanism has been utilized to explain the catalyzed decomposition of several cyclic and linear peroxides, including diphenoyl peroxide (4), peroxyesters and 1,2-dioxetanones. Special interest has focused on this mechanism when it was utilized to explain the efficient excited state formation in the chemiexcitation step of the firefly s luciferin/luciferase bio luminescence. However, doubts have been voiced more recently about the validity of this mechanistic scheme, due to divergences about the... 

The unimolecular decomposition of 1,2-dioxetanes and 1,2-dioxetanones (a-peroxylac-tones) is the simplest and most exhaustively studied example of a thermal reaction that leads to the formation, in this case in a single elementary step, of the electronically excited state of one of the product molecules. The mechanism of this transformation was studied intensively in the 1970s and early 1980s and several hundreds of 1,2-dioxetane derivatives and some 1,2-dioxetanones were synthesized and their activation parameters and CL quantum yields determined. Thermal decomposition of these cyclic peroxides leads mainly to the formation of triplet-excited carbonyl products in up to 30% yields. However, formation of singlet excited products occurs in significantly lower yields (below... 

Intensive studies in the field of mechanistic CL by several research groups have resulted in the description of a large variety of peroxides which, in the presence of appropriate activators, show decomposition in an activated CL process and might involve the CIEEL mechanism . Even before the formulation of the CIEEL mechanism, Rauhut s research group obtained evidence of the involvement of electron-transfer processes in the excitation step of the peroxyoxalate CL. Results obtained in the activated CL of diphe-noyl peroxide (4) led to the formulation of this chemiexcitation mechanism , and several 1,2-dioxetanones (a-peroxylactones), such as 3,3-dimethyl-l,2-dioxetanone (9) and the first a-peroxylactone synthesized, 3-ierr-butyl-l,2-dioxetanone (14), have been shown to possess similar CL properties, compatible with the CIEEL mechanism Furthermore, the CL properties of secondary peroxyesters, such as 1-phenethylperoxy acetate (15) , peroxylates (16) , o-xylylene peroxide (17) , malonyl peroxides... 

While the unimolecular chemiluminescence of dioxetanones appears to fall easily within the framework of conventional dioxetane chemiluminescence, the chemiluminescence of dioxetanones in the presence of certain fluorescers falls resoundingly outside that framework. Adam et al. (1974) noted that the addition of rubrene to solutions of dimethyldioxetanone gave a yield of light twenty times that obtained when an equivalent concentration of 9,10-diphenylanthracene was added. Importantly, the apparent dissimilarity between rubrene and diphenylanthracene is inexplicable by any conventional mechanism of dioxetane decomposition. Also, significantly, Adam et al. (1974) observed an increase in the first-order decay constant of the dioxetanone with the addition of rubrene, an observation for which they did not offer an explanation. Sawaki and Ogata (1977) also observed an unusual dependence of the chemiluminescence yield on the identity of added fluorescer in the base-catalyzed decomposition of or-hydroperoxyesters, for which a dioxetanone intermediate was proposed (25). 

Takano Y, Tsunesada T, Isobe H, Yoshioka Y, Yamaguchi K, and Saito I. Theoretical studies of decomposition reactions of dioxetane, dioxetanone, and related species. CT induced luminescence mechanism revisited. Bull Chem Soc Jpn 1999 72 213-25. 

The thermolysis of dimethyl-dioxetanone (21) revealed two different mechanisms of decomposition. In a unimolecular mechanism, the dioxetanone is cleaved into CO2 and acetone in its excited triplet state (19) ... 

Although there are many components in a mechanistic description of a chemiluminescent reaction, the heart of the matter is the actual excitation step. Several such steps have been identified. Some are molecular in character e. g. the decomposition of dioxetans and some are intermolecular electron transfer steps. There is an intermediate class in which the step can be formulated as an /n ramolecular electron transfer. Many luminescent reactions have been ascribed to this category with varying degrees of confidence. Cyclic hydrazides such as luminol belong rather uncertainly here. Electron rich dioxetans and dioxetanones and the luciferins with such intermediates on the pathway are a little more reasonably assigned to an intramolecular electron transfer mechanism. Even here however caution is required in that direct evidence for discrete electron transfer will by its very nature be almost impossible to obtain and will probably remain circumstantial. 

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