Figure 1
Classical chemiluminescent reactions: (a) luminol; (b) lucigenin; (c) peroxyoxalate (adapted from reference 44 Baader, W. J.; Stevani, C. V.; Bechara, E. J. H.; Rev. Virtual Quim.2015, 7, 74.).
Figure 2
Thermal cleavage of 1,2-dioxetanes and 1,2-dioxetanones leading to two carbonyl products, one of them in an electronically excited state, preferentially in the triplet manifold. Reproduced from reference 4, by permission from the Rev. Virtual de Química.
Figure 3
Chemically initiated electron exchange luminescence (CIEEL) mechanism proposed for the decomposition of a 1,2-dioxetanone catalyzed by an activator (ACT) with low oxidation potential (adapted from reference 44 Baader, W. J.; Stevani, C. V.; Bechara, E. J. H.; Rev. Virtual Quim.2015, 7, 74.).
Figure 4
Mechanism for the induced decomposition of protected phenoxy-substituted 1,2-dioxetanes. Reproduced from reference 4, by permission from the Rev. Virtual de Química.
Figure 2
Thermal cleavage of 1,2-dioxetanes and 1,2-dioxetanones leading to two carbonyl products, one of them in an electronically excited state, preferentially in the triplet manifold. Reproduced from reference 4, by permission from the Rev. Virtual de Química.
Figure 3
Chemically initiated electron exchange luminescence (CIEEL) mechanism proposed for the decomposition of a 1,2-dioxetanone catalyzed by an activator (ACT) with low oxidation potential (adapted from reference 44 Baader, W. J.; Stevani, C. V.; Bechara, E. J. H.; Rev. Virtual Quim.2015, 7, 74.).
Figure 4
Mechanism for the induced decomposition of protected phenoxy-substituted 1,2-dioxetanes. Reproduced from reference 4, by permission from the Rev. Virtual de Química.
Figure 5
Photophysical and photochemical transformations of acetone upon excitation to singlet and triplet states (*); (i) thermal deactivation; (ii) fluorescence and phosphorescence emission; (iii) energy transfer to an acceptor molecule (A), possibly followed by photophysical (hν, heat) or photochemical processes of A (photoproducts); (iv) energy transfer from triplet acetone to molecular oxygen, generating highly reactive singlet oxygen; (v) 1,2-cycloaddition to alkenes, yielding an oxetane (Patern®- Büchi reaction); (vi) hydrogen abstraction from suitable H-donors like alcohols and 1,4-dienes, leading to (vii) the reduction product 2-propanol and dimerization product 2,3-dihydroxy-2,3-dimethylbutane (pinacol); (viii) C−C bond homolysis (α-cleavage) to a methyl and an acetyl radical, which can undergo decarbonylation or dimerization to diacetyl4040 Oliveira, T. F.; Silva, A. L. M.; Moura, R. A.; Bagattini, R.; Oliveira, A. A. F.; Medeiros, M. H. G.; di Mascio, P.; Campos, I. P. A.; Barreto, F. P.; Bechara, E. J. H.; Loureiro, A. P. M.; Sci. Rep.2014, 4, 5359. (adapted from reference 4).
Figure 6
The hypothesis of "photochemistry in the dark": typical photochemical products can arise in the absence of light in vitro or in vivo from electronically excited molecules generated by non-enzymatic and enzymatic reactions. Triplet carbonyl species are the best candidates for excited products due to their long lifetimes and oxyl radical-like structure and behavior (insert).
Figure 7
Photochemical and dioxetane-induced cis,trans-isomerization of stilbene and analogous reaction of cinnamic acid in sweet clover (Melilotus albus) (adapted from reference 4).
Figure 8
[2 + 2] Cycloaddition and cis,trans-isomerization driven by excited acetone in a model system with 1,2-dicyanoethylene and hypothetical "dark" dimerization of cinnamic acid in coca. TMD: tetramethyl-1,2-dioxetane (adapted from reference 4).
Figure 9
Isomerization of santonin to lumisantonin in absinthe, either photochemical or induced by chemically-generated triplet acetone (adapted from reference 4).
Figure 10
Disrotatory electrocyclic ring closure of colchicine into isomeric β- and γ-lumicolchicines, under sunlight radiation or in underground corms of autumn crocus Colchicum autumnale. Continuous exposure of colchicine to light leads to the dimerization of β-lumicolchicine to the cyclobutene derivative α-lumicolchicine (adapted from reference 4).
Figure 11
Typical reactions of free radicals centered on carbon, oxygen or other atoms (adapted from reference 4).
Figure 12
Generation of triplet acetone by the horseradish peroxidase (HRP)-catalyzed oxidation of isobutanal (IBAL). The substrate evokes firefly luciferin with respect to the presence of a carbonyl-activated hydrogen atom, insertion of oxygen in the α-carbon yielding an α-hydroperoxide (IBAL-OOH), cyclization to a hypothetical 1,2-dioxetane (IBALO2), whose cleavage yields triplet acetone, which decays by light emission and reduction to isopropanol and pinacol.5151 Velosa, A. C.; Baader, W. J.; Stevani, C. V.; Mano, C. M.; Bechara, E. J. H.; Chem. Res. Toxicol.2007, 20, 1162. Reproduced from reference 4, by permission of Rev. Virtual de Química.
Figure 13
Possible biological sources of triplet ketones. Apart from 1,2-dioxetane decomposition, triplet ketones can be formed by dismutation of alkoxy and alkylperoxy radicals occurring in the propagation and termination steps of lipid peroxidation, in addition to the reported retro-Paternò-Büchi reaction of the oxetane derivative from a ketone and thymine (adapted from reference 4).
Figure 14
HRP-catalyzed or peroxynitrite (ONOO−)-initiated aerobic oxidation of methyl acetoacetone (MAA) to acetate and triplet excited diacetyl (adapted from reference 4).
Figure 15
HRP-catalyzed oxidation of 2-phenylpropanal (R = Me) and diphenylacetaldehyde (R = Ph) to acetophenone and benzophenone, respectively, in the triplet state (adapted from reference 4).
Figure 16
Target molecules for triplet acetone generated by isobutanal/HRP. Pr and Pfr, red-absorbing and far-red absorbing phytochromes; 9,10-dibromoanthracene (DBA); xanthene dyes: fluorescein, eosin and rose bengal; indoles, tryptophan and plant hormones (adapted from reference 4).
Figure 17
Dimerization of thymine induced by triplet acetone generated from the thermolysis of 3,3,4-trimethyl-1,2-dioxetane and retro-reaction promoted by irradiation at 254 nm.
Figure18
Attendees of the International Conference on Chemi- and Bioenergized Processes, held in 1978 in Guarujá (SP, Brazil). From left to right: 1st row (seated): Edy Rivas, Carmem Vidigal, Michael Kasha, John Woodland ("Woody") Hastings, Eduardo Lissi, Etelvino Bechara; 2nd row: Christopher Foote, Giuseppe Cilento, Waldemar Adam, Frank M. Thérèse Wilson; 3rd row: William Richardson, Adelaide Faljoni-Alário, Ohara Augusto, Rex Tyrrell, Roberto C. de Baptista, Paul Schaap, Nelson Duran, Marcela Haún; 4th row: Gary B. Schuster, Norman Krinsky, Pill-Soon Song, Alfons Baumstark, K. Zaklika, Yoshitaki Shimizu, Rogerio Meneghini; 5th row: R. Srinivasan, Karl Kopecky, Klaus Zinner, Frank Quina, Bechara Kachar.
Figure 7
Photochemical and dioxetane-induced cis,trans-isomerization of stilbene and analogous reaction of cinnamic acid in sweet clover (Melilotus albus) (adapted from reference 4).
Figure 8
[2 + 2] Cycloaddition and cis,trans-isomerization driven by excited acetone in a model system with 1,2-dicyanoethylene and hypothetical "dark" dimerization of cinnamic acid in coca. TMD: tetramethyl-1,2-dioxetane (adapted from reference 4).
Figure 9
Isomerization of santonin to lumisantonin in absinthe, either photochemical or induced by chemically-generated triplet acetone (adapted from reference 4).
Figure 10
Disrotatory electrocyclic ring closure of colchicine into isomeric β- and γ-lumicolchicines, under sunlight radiation or in underground corms of autumn crocus Colchicum autumnale. Continuous exposure of colchicine to light leads to the dimerization of β-lumicolchicine to the cyclobutene derivative α-lumicolchicine (adapted from reference 4).
Figure 11
Typical reactions of free radicals centered on carbon, oxygen or other atoms (adapted from reference 4).
Figure 12
Generation of triplet acetone by the horseradish peroxidase (HRP)-catalyzed oxidation of isobutanal (IBAL). The substrate evokes firefly luciferin with respect to the presence of a carbonyl-activated hydrogen atom, insertion of oxygen in the α-carbon yielding an α-hydroperoxide (IBAL-OOH), cyclization to a hypothetical 1,2-dioxetane (IBALO2), whose cleavage yields triplet acetone, which decays by light emission and reduction to isopropanol and pinacol.5151 Velosa, A. C.; Baader, W. J.; Stevani, C. V.; Mano, C. M.; Bechara, E. J. H.; Chem. Res. Toxicol.2007, 20, 1162. Reproduced from reference 4, by permission of Rev. Virtual de Química.
Figure 13
Possible biological sources of triplet ketones. Apart from 1,2-dioxetane decomposition, triplet ketones can be formed by dismutation of alkoxy and alkylperoxy radicals occurring in the propagation and termination steps of lipid peroxidation, in addition to the reported retro-Paternò-Büchi reaction of the oxetane derivative from a ketone and thymine (adapted from reference 4).
Figure 14
HRP-catalyzed or peroxynitrite (ONOO−)-initiated aerobic oxidation of methyl acetoacetone (MAA) to acetate and triplet excited diacetyl (adapted from reference 4).
Figure 15
HRP-catalyzed oxidation of 2-phenylpropanal (R = Me) and diphenylacetaldehyde (R = Ph) to acetophenone and benzophenone, respectively, in the triplet state (adapted from reference 4).
Figure 16
Target molecules for triplet acetone generated by isobutanal/HRP. Pr and Pfr, red-absorbing and far-red absorbing phytochromes; 9,10-dibromoanthracene (DBA); xanthene dyes: fluorescein, eosin and rose bengal; indoles, tryptophan and plant hormones (adapted from reference 4).
Figure 17
Dimerization of thymine induced by triplet acetone generated from the thermolysis of 3,3,4-trimethyl-1,2-dioxetane and retro-reaction promoted by irradiation at 254 nm.
Figure18
Attendees of the International Conference on Chemi- and Bioenergized Processes, held in 1978 in Guarujá (SP, Brazil). From left to right: 1st row (seated): Edy Rivas, Carmem Vidigal, Michael Kasha, John Woodland ("Woody") Hastings, Eduardo Lissi, Etelvino Bechara; 2nd row: Christopher Foote, Giuseppe Cilento, Waldemar Adam, Frank M. Thérèse Wilson; 3rd row: William Richardson, Adelaide Faljoni-Alário, Ohara Augusto, Rex Tyrrell, Roberto C. de Baptista, Paul Schaap, Nelson Duran, Marcela Haún; 4th row: Gary B. Schuster, Norman Krinsky, Pill-Soon Song, Alfons Baumstark, K. Zaklika, Yoshitaki Shimizu, Rogerio Meneghini; 5th row: R. Srinivasan, Karl Kopecky, Klaus Zinner, Frank Quina, Bechara Kachar.
Figure 19
Phosphate-induced amplification of the mitochondrial membrane peroxidation chain by triplet carbonyls. (i) Peroxidation mechanism of polyunsaturated fatty acids (PUFAs) yielding triplet carbonyls (e.g., n-hexanal), singlet oxygen, and PUFA hydroperoxides (PUFAOOH); (ii) initiation of additional peroxidation chains takes place (propagation step) by abstraction of double allylic hydrogen atoms from PUFAs by triplet carbonyls, thereby initiating new peroxidation chains, whereas singlet oxygen adds to PUFAs also producing hydroperoxides; (iii) pathways (ii) and (iii) also show ultra-weak green light emission by triplet carbonyls and red light emission by singlet oxygen; (iv) phosphate-catalyzed enolization of peroxidation aldehyde products that amplify membrane peroxidation. ROS, reactive oxygen species; cyt c, cytochrome c; A3*, triplet carbonyl product from lipoperoxidation (adapted from reference 4).
Figure 20
"Dark" generation of cyclobutane pyrimidine dimers (CPDs) several hours after melanocyte exposure to UVA,B light. Red arrows: solar UVA and UVB light is absorbed by the DNA thymine and cytosine bases of skin melanocytes, yielding their electronically excited states, which undergo [2 + 2] cycloaddition within picoseconds to the mutagenic pyrimidine dimers: C=C, C=T, and predominantly T=T. Grey arrows: concomitantly, UV light induces melanin synthesis, the natural skin solar protection pigment, and activation of nitric oxide synthase (NOS) and NADPH oxidase, respectively, sources of superoxide radical (O2•−) and nitric oxide (NO•) whose diffusion-controlled reaction produces peroxynitrite (ONOO−). These reactive oxygen species (ROS) continuously attack melanin, leading to its fragmentation. The melanin derivatives migrate to the nuclear space where they are oxidized by peroxynitrite to a hypothetical dioxetane indole intermediate, whose cleavage yields a kynurenine analogue excited to triplet state. Exothermic energy transfer from the triplet carbonyl product to adjacent T and C residues produces a blend of T=T, C=C, and predominantly T=C, which is a pre-mutagenic C→T transition that is reportedly a melanoma signature. Parallel oxidative damage to guanosine also reportedly promotes G→T mutations that may lead to apoptosis (adapted from reference 70).
Figure 21
Sources, targets and biological response of singlet oxygen (adapted from reference 4).
Figure 22
Generation of singlet oxygen (1∆g) by energy transfer from enzymatically (a) and chemically (b) produced triplet acetone to ground state (3σg) molecular oxygen.
Figure 23
Reaction mechanism of peroxynitrite addition to diacetyl, methylglyoxal, and glyoxal, ultimately leading to acetic acid, acetic acid plus formic acid, and formic acid. The acetyl radical intermediate attaches to added amino acids and nucleobases, whereas formyl radical inserts ground state oxygen (3σg−) to form formyl peroxyl radical, whose annihilation yields highly reactive singlet oxygen (1∆g). Singlet oxygen was scavenged by a water-soluble anthracene derivative (AVS) and the corresponding 9,10-endoperoxide (AVSO2) adduct was identified by HPLC-MS.
Figure 20
"Dark" generation of cyclobutane pyrimidine dimers (CPDs) several hours after melanocyte exposure to UVA,B light. Red arrows: solar UVA and UVB light is absorbed by the DNA thymine and cytosine bases of skin melanocytes, yielding their electronically excited states, which undergo [2 + 2] cycloaddition within picoseconds to the mutagenic pyrimidine dimers: C=C, C=T, and predominantly T=T. Grey arrows: concomitantly, UV light induces melanin synthesis, the natural skin solar protection pigment, and activation of nitric oxide synthase (NOS) and NADPH oxidase, respectively, sources of superoxide radical (O2•−) and nitric oxide (NO•) whose diffusion-controlled reaction produces peroxynitrite (ONOO−). These reactive oxygen species (ROS) continuously attack melanin, leading to its fragmentation. The melanin derivatives migrate to the nuclear space where they are oxidized by peroxynitrite to a hypothetical dioxetane indole intermediate, whose cleavage yields a kynurenine analogue excited to triplet state. Exothermic energy transfer from the triplet carbonyl product to adjacent T and C residues produces a blend of T=T, C=C, and predominantly T=C, which is a pre-mutagenic C→T transition that is reportedly a melanoma signature. Parallel oxidative damage to guanosine also reportedly promotes G→T mutations that may lead to apoptosis (adapted from reference 70).
Figure 21
Sources, targets and biological response of singlet oxygen (adapted from reference 4).
Figure 22
Generation of singlet oxygen (1∆g) by energy transfer from enzymatically (a) and chemically (b) produced triplet acetone to ground state (3σg) molecular oxygen.
Figure 23
Reaction mechanism of peroxynitrite addition to diacetyl, methylglyoxal, and glyoxal, ultimately leading to acetic acid, acetic acid plus formic acid, and formic acid. The acetyl radical intermediate attaches to added amino acids and nucleobases, whereas formyl radical inserts ground state oxygen (3σg−) to form formyl peroxyl radical, whose annihilation yields highly reactive singlet oxygen (1∆g). Singlet oxygen was scavenged by a water-soluble anthracene derivative (AVS) and the corresponding 9,10-endoperoxide (AVSO2) adduct was identified by HPLC-MS.
