Reactions Of Singlet Molecular Oxygen Research Articles

Bypassing the multireference character of singlet molecular oxygen, part 1:1,4‐cyclo‐addition

AbstractModeling reactions involving singlet molecular oxygen (O2 [1Δg]) is challenging because the degeneracy of the highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO and LUMO) orbitals of oxygen causes a significant multireference character. Within the limit that singlet‐singlet near‐degeneracy disappears in the transition state, it would be possible to bypass singlet oxygen's multireference character by simply adding the experimentally determined singlet/triplet splitting (22.5 kcal/mol) to the energy of the triplet ground state of molecular oxygen. This method is tested by calculating rate constants for the reactions of singlet molecular oxygen with furan, 2‐methylfuran, 2,5‐dimethylfuran, pyrrole, 2‐methylpyrrole, 2,5‐dimethylpyrrole, and cyclopentadiene using transition state theory. We find that the reaction rate coefficients are within a factor of 15 of experimentally determined rate constants, indicating an error in the barrier energy of roughly 3 kcal/mol. Furthermore, we find that energy refinement at the CCSD(T)‐F12 level of theory is crucial to achieving accurate results. We conclude that, based on a comparison with an experiment, this approximation is valid to some degree and can be used for other systems involving the 1,4‐cyclo‐addition of singlet oxygen.

Probing the reactivity of singlet oxygen with purines.

The reaction of singlet molecular oxygen with purine DNA bases is investigated by computational means. We support the formation of a transient endoperoxide for guanine and by classical molecular dynamics simulations we demonstrate that the formation of this adduct does not affect the B-helicity. We thus identify the guanine endoperoxide as a key intermediate, confirming a low-temperature nuclear magnetic resonance proof of its existence, and we delineate its degradation pathway, tracing back the preferential formation of 8-oxoguanine versus spiro-derivates in B-DNA. Finally, the latter oxidized 8-oxodGuo product exhibits an almost barrierless reaction profile, and hence is found, coherently with experience, to be much more reactive than guanine itself. On the contrary, in agreement with experimental observations, singlet-oxygen reactivity onto adenine is kinetically blocked by a higher energy transition state.

Singlet oxygen and natural substrates: functional polyunsaturated models for the photooxidative degradation of carotenoids

Abstract The primary chemical reactions of singlet molecular oxygen with polyunsaturated carotenoids are the focus of this research report. Model compounds that exhibit electronic properties and substituent pattern similar to natural carotenes, xanthophylls or apocarotenoids, respectively, were investigated with regard to photooxygenation reactivity. For dienes and trienes as substrates, high tandem reactivity was observed and hydroperoxy-endoperoxides were isolated as the secondary products of singlet oxygen reaction. The electronic gem-effect on the regioselectivity of the ene reaction is conserved also in vinylogous positions and thus appears to originate from a radical-stabilizing effect. In an attempt to combine different peroxide groups derived from natural products as a tool for new pharmaceutically active products, a dyade synthesis of an artemisinine-safranol with subsequent singlet oxygen addition was realized.

An (1)O2 route to γ-hydroxyalkenal phospholipids by vitamin E-induced fragmentation of hydroperoxydiene-derived endoperoxides.

Biologically active phospholipids that incorporate an oxidatively truncated acyl chain terminated by a γ-hydroxyalkenal are generated in vivo. The γ-hydroxyalkenal moiety protrudes from lipid bilayers like whiskers that serve as ligands for the scavenger receptor CD36, fostering endocytosis, e.g., of oxidatively damaged photoreceptor cell outer segments by retinal pigmented endothelial cells. They also covalently modify proteins generating carboxyalkyl pyrroles incorporating the ε-amino group of protein lysyl residues. We postulated that γ-hydroxyalkenals could be generated, e.g., in the eye, through fragmentation of hydroperoxy endoperoxides produced in the retina through reactions of singlet molecular oxygen with polyunsaturated phospholipids. Since phospholipid esters are far more abundant in the retina than free fatty acids, we examined the influence of a membrane environment on the fate of hydroperoxy endoperoxides. We now report that linoleate hydroperoxy endoperoxides in thin films and their phospholipid esters in biomimetic membranes fragment to γ-hydroxyalkenals, and fragmentation is stoichiometrically induced by vitamin E. The product distribution from fragmentation of the free acid in the homogeneous environment of a thin film is remarkably different from that from the corresponding phospholipid in a membrane. In the membrane, further oxidation of the initially formed γ-hydroxyalkenal to a butenolide is disfavored. A conformational preference for the γ-hydroxyalkenal, to protrude from the membrane into the aqueous phase, may protect it from oxidation induced by lipid hydroperoxides that remain buried in the lipophilic membrane core.

Generation of Cholesterol Carboxyaldehyde by the Reaction of Singlet Molecular Oxygen [O2 (1Δg)] as Well as Ozone with Cholesterol

A few years ago, it was reported that ozone is produced in human atherosclerotic arteries, on the basis of the identification of 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al and 3beta-hydroxy-5beta-hydroxy-B-norcholestane-6beta-carboxaldehyde (ChAld) as their 2,4-dinitrophenylhydrazones. The formation of endogenous ozone was attributed to water oxidation catalyzed by antibodies, with the formation of dihydrogen trioxide as a key intermediate. We now report that ChAld is also generated by the reaction of cholesterol with singlet molecular oxygen [O2 (1Delta(g))] that is produced by photodynamic action or by the thermodecomposition of 1,4-dimethylnaphthalene endoperoxide, a defined pure chemical source of O2 (1Delta(g)). On the basis of 18O-labeled ChAld mass spectrometry, NMR, light emission measurements, and derivatization studies, we propose that the mechanism of ChAld generation involves the formation of the well-known cholesterol 5alpha-hydroperoxide (5alpha-OOH) (the major product of O2 ((1)Delta(g))-oxidation of cholesterol) and/or a 1,2-dioxetane intermediate formed by O2 (1Delta(g)) attack at the Delta(5) position. The Hock cleavage of 5alpha-OOH (the major pathway) or unstable cholesterol dioxetane decomposition (a minor pathway, traces) gives a 5,6-secosterol intermediate, which undergoes intramolecular aldolization to yield ChAld. These results show clearly and unequivocally that ChAld is generated upon the reaction of cholesterol with O2 (1Delta(g)) and raises questions about the role of ozone in biological processes.

Monitoring the Formation and Decay of Singlet Molecular Oxygen in TiO2 Photocatalytic Systems and the Reaction with Organic Molecules

By monitoring the time profiles of 1O2 at the 1270-nm band, the reaction of singlet molecular oxygen (1O2) with four kinds of organic molecules, methionine, pyrrole, collagen, and folic acid was examined in photocatalytic systems of TiO2 aqueous suspension. A fast decay observed in 1.5 µs after the pulse excitation attributable to the fast reaction of formed 1O2 with these molecules. From the analysis of the decay profiles, it is concluded that the organic molecules should be adsorbed on the TiO2 surface to react with 1O2.

Solvent effect on the sensitized photooxygenation of cyclic and acyclic α-diimines

The reaction of singlet molecular oxygen with a series of cyclic and acyclic α-diimines was studied. Time-resolved methods were used to measure total reaction rate constants and steady-state methods were used to determine chemical reaction rate constants. GC–MS was used to tentatively assign the reaction products. 5,6-Disubstituted cyclic α-diimines are singlet oxygen quenchers, but become more effective in polar solvents. A reaction mechanism involving a perepoxide intermediate or transition state leading to a hydroperoxide seems to be a key reaction path for product formation. A replacement of the phenyl substituent for a methyl substituent opens up an additional reaction involving a perepoxide-like exciplex, which increases singlet oxygen quenching of the cyclic α-diimines. The reactivity of 5,6-disubstituted cyclic α-diimines towards singlet oxygen is highly dependent on steric interactions arising from vicinal phenyl rings and from electronic effects. 1,4-Disubstituted acyclic α-diimines are, by comparison, moderate or poor singlet oxygen quenchers. Total rate constants are scarcely dependent on solvent properties, but instead correlate with the Hildebrand parameter. These results are explained in terms of a mechanism involving a dioxetane-like exciplex that gives rise to a charged intermediate leading to products.

Oxyfunctionalization of Alkenes by Dye‐Sensitized Intrazeolite Photooxygenation

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reaction of singlet molecular oxygen, O 2( 1Δ g), with the Cinchona tree alkaloids : Effect of absolute configuration on the total rate constant

Detection of O 2( 1Δ g) emission, λ max = 1270 nm, following laser excitation and steady-state methods were employed to measure the total reaction rate constant, k T, and the reactive reaction rate constant, k R, for the reaction between singlet oxygen and the Cinchona tree alkaloids, cinchonidine, cinchonine, quinine and quinidine in several solvents. In most solvents, the k T values were close to 10 7 M −1 s −1, indicating that these compounds are good singlet oxygen quenchers. The reactive rate constants are smaller than 10 4 M −1 s −1, implying that quenching is essentially a physical process. The analysis of solvent effect on k T by using LSER equations indicates that singlet oxygen deactivation by these drugs is accelerated by solvents with large π * and β values, being inhibited by hydrogen bond donor (HBD) solvents. Correlations employing theoretical solvent parameters, TLSER, give similar results. These data support the formation of an exciplex with charge transfer character, resulting from the singlet oxygen electrophilic attack on the quinuclidine moiety nitrogen. In most solvents, cinchonidine is more reactive than cinchonine and quinine is more reactive than quinidine although reactivity differences are small and only in a few solvents k T values of the S, R-isomer are about twice than those of R, S-isomer. The higher reactivity of S, R-isomers in these solvents is explained by the geometrically favorable intra-exciplex stabilizing interaction between the non-bonded pernitrone oxygen and the hydrogen of the hydroxyl substituent at C(9).

Oxyfunctionalization of Alkenes by Dye-Sensitized Intrazeolite Photooxygenation

This review focuses on the recent achievements towards the selective formation of allylic hydroperoxides by the reaction of singlet molecular oxygen ( 1 O 2) with alkenes adsorbed in the cavities of zeolite Na-Y. The product distribution by zeolite confinement is often dramatically different compared to the photooxygenation reaction in a homogeneous medium. Cation - π interactions and cation - singlet oxygen interactions, in the rate-limiting transition states, are most likely responsible for the changes in product selectivity within Na-Y. STRUCTURAL FEATURES OF FAUJASITES Zeolites are crystalline aluminosilicates whose primary structure is formed by SiO4 4- and AlO4 5- tetrahedra sharing the edges (1). Their tertiary structure forms strictly uniform channels and cavities of molecular dimensions that are repeated along the zeolite lattice. Due to the lower valence of the aluminum relative to silicon, the excess negative charge (one per Al atom) is balanced by alkali metal cations, mainly Na + . The cations are placed in the interior of cavities and can be easily exchanged. The cation-exchange process leads to new type of materials having interesting properties (2), and it is expected in the near future that the metal- supported zeolites will find significant applications in applied chemistry.

Participation of singlet oxygen in ultraviolet-a-induced lipid peroxidation in mouse skin and its inhibition by dietary β-carotene: an ex vivo study

Dietary β-carotene acts as a photoprotective agent in the skin, but the exact mechanism of protection is unknown. This ex vivo study is focused on determining the mechanism of action of β-carotene against UV-A-induced skin damage by characterizing peroxidized phosphatidylcholine (PC) and β-carotene oxidation products. BALB/c mice were fed with basal or a β-carotene-supplemented diet, and homogenates from their dorsal skin were prepared after 3 weeks for UV-A irradiation. Analyses revealed that the degree of lipid peroxidation in the β-carotene group was significantly lower than that in the controls. The isomeric composition of hydroperoxy fatty acids, constituting peroxidized PC, was determined by thin-layer chromatography-blotting followed by gas chromatography/mass spectrometry (MS)/selected ion monitoring analysis. The 9- and 10-isomers of peroxidized PC, resulting from the reaction of singlet molecular oxygen ( 1O 2) with oleic acid, were elevated in the UV-A-exposed control group compared to the experimental group. Similar results were obtained from methylene-blue-sensitized photooxidation of mouse skin lipids in vitro. Liquid chromatography/MS analysis of the homogenates confirmed the formation of β-carotene 5,8-endoperoxide, a specific marker for the 1O 2 reaction. These results indicate that dietary β-carotene accumulates in the skin and acts as a protective agent against UV-A-induced oxidative damage, by quenching the 1O 2.

Solvent effects on reactions of singlet molecular oxygen, O2(1Δg), with antimalarial drugs

Detection of O2(1Δg) emission, λmax=1270nm, following laser excitation and steady-state methods were employed to measure total reaction rate constants, kT, for the reaction between singlet oxygen and the antimalarial drugs quinine (QU), quinacrine (QC), chloroquine (CQ) and amodiaquine (AQ) in several solvents. Values for kT range from 0.45±0.03×107M−1s−1 for AQ in benzene to 25.1±0.88×107M−1s−1 for CQ in N,N-dimethylformamide. Analysis of solvent effect on kT for QU, QC, and CQ by using the LSER formalism indicates that singlet oxygen deactivation by these drugs is accelerated by solvents with large π∗ values and hydrogen bond acceptor (HBA) properties and is inhibited by hydrogen bond donors (HBD) solvents. This result support the formation of an exciplex intermediate of charge transfer character, as proposed for reactions of tertiary amines with singlet oxygen, process largely governed by physical quenching. AQ behaves in a different manner. The LSER equation for this drug shows that kT increases in solvents with large π∗ values and diminishes in HBD solvents. In this case, reaction mechanism probably involves a partially concerted cycloaddition of singlet oxygen to the aminophenolic ring in position 4.

Singlet oxygen-mediated damage to cellular DNA determined by the comet assay associated with DNA repair enzymes.

The damage profile produced by the reaction of singlet molecular oxygen with cellular DNA was determined using the comet assay associated with DNA repair enzymes. Singlet oxygen was produced intracellularly by thermal decomposition of a water-soluble endoperoxide of a naphthalene derivative which is able to penetrate through the membrane into mammalian cells. We found that the DNA modifications produced by singlet oxygen were almost exclusively oxidised purines recognised by the formamidopyrimidine DNA N-glycosylase. In contrast, significant amounts of direct strand breaks and alkali-labile sites or oxidised pyrimidines, detectable by the bacterial endonuclease III, were not produced.

Electron transfer reactions of singlet molecular oxygen with phenols

The correlation of the reactive component of the bimolecular quenching rate constant, kr, with ΔG for reactions of singlet molecular oxygen with phenols is interpreted in terms of classical and semiclassical theories of electron transfer. Both treatments indicate a diabatic process with a reorganization energy of about 0.46 eV. The observed diabaticity is in line with a crossing of states with different symmetry. Similar results were obtained for the reactions of singlet molecular oxygen with phenoxide ions in water. Copyright © 2000 John Wiley & Sons, Ltd.

CASSCF, MP2, and CASMP2 studies on addition reaction of singlet molecular oxygen to ethylene molecule

The reaction mechanism and relative stabilities of the intermediates and transition states in the reaction of 1O2 plus ethylene molecule using ab initio molecular orbital (MO) theories at several levels of theory with the correction of the nondynamic and dynamic electron correlation effects were systematically investigated. Full geometry optimizations of the corresponding biradical (BR) intermediates, perepoxide (PE) and 1,2-dioxetane (DO) were performed by complete-active-space CASSCF{2,2}/6-31G* method with nondynamic electron correlation effect and Moller-Plesset MP2/6-31G* method with dynamic electron correlation effect. For the 1,4-biradical intermediates, new gauche-type 1BR state was found at both CASSCF and MP2 levels, corresponding to the transition state of the rotation motion of the O2 moiety. It was found from the intrinsic-reaction-coordinate (IRC) study that another gauche-type 1BR transition state connects smoothly to the reactant system 1O2+H2C(DOUBLE BOND)CH2 and the gauche minimum 1BR state, showing that the reaction through the 1,4-biradical intermediates initially proceeds through the gauche transition state to form the gauche minimum 1BR state, following that the free rotation of O2 moiety occurs due to the energy barrier less than 4.0 kcal/mol. The stability of the perepoxide is surprisingly sensitive to the levels of the theory and the basis sets employed. The coupled-cluster methods, CCSD and CCSD(T), gave the reasonable stabilities of 1,4-biradical intermediates, perepoxide, and dioxetane as a reaction product. From the results of the CCSD and CCSD(T) methods, the reaction of 1O2+H2C(DOUBLE BOND)CH2 proceeds by a two-step mechanism through the 1,4-biradical intermediates rather than through the perepoxide. © 1997 John Wiley & Sons, Inc. Int J Quant Chem 65: 787–801, 1997

Rapid Reaction of Singlet Molecular Oxygen (1O2) with p-Aminobenzoic Acid (PABA) in Aqueous Solution

The reaction of singlet molecular oxygen (1O2) with p-aminobenzoic acid (PABA) is quite rapid. The rate constant for reaction of 1O2 with PABA was measured in buffered aqueous solution by the method of competition kinetics and found to be 8.9×108 M−1 sec−1. The results of a Stern-Volmer analysis indicate that additional loss of 1O2 does not occur through physical quenching by PABA. Although illuminated PABA solutions are known to form 1O2, it appears that PABA is also a very efficient sink for 1O2.

Reaction of singlet oxygen with 2'-deoxyguanosine and DNA. Isolation and characterization of the main oxidation products.

The reaction of singlet molecular oxygen with 2'-deoxyguanosine and DNA was studied. Emphasis was placed on the identification and characterization of the main methylene blue mediated type II (singlet oxygen) oxidation products of 2'-deoxyguanosine and its corresponding 3',5'-di-O-acetylated derivative. Two major oxidation products of 2'-deoxyguanosine were isolated and characterized by mass spectrometry analysis and extensive 1H and 13C NMR measurements as the two 4R* and 4S* diastereomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine. The addition of 1O2 was also found to occur to the base moiety of the corresponding 3',5'-di-O-acetylated derivative. Methylene blue mediated photosensitization of 2'-deoxyguanosine led also to the production of 7,8-dihydro-8-oxo-2'-deoxyguanosine, but in a relatively lower yield with respect to the two above diastereomers. The participation of singlet oxygen in the mechanism of formation of these oxidation products was confirmed. A reasonable mechanism involving the transient formation of an unstable endoperoxide produced through a Diels-Alder 1,4-cycloaddition of singlet oxygen to the purine ring is suggested. Quantitative analysis allowed us to demonstrate that the two diastereomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine are the main singlet oxygen oxidation products of the guanine moiety within nucleosides, whereas 7,8-dihydro-8-oxoguanine was found to be the major 1O2 oxidation product of guanine in double-stranded DNA.

Reaction of singlet molecular oxygen with tetramethyl- o-xylylene

We describe here the evaluation of the rate constant of reaction of singlet molecular oxygen with tetramethyl- o-xylylene, an intermediate in the photolysis of 1,1,3,3-tetramethyl- 2-indanone. This is a rare example of quantitative analysis of transient-transient reaction kinetics between two different intermediates; the rate constant, 3.2 × 10 8 M −1 s −1, demonstrates the efficient nature of the reaction.

Theoretical Studies on the 1,2-Cycloaddition Reaction of Singlet Molecular Oxygen (<sup>1</sup>O<SUB>2</SUB>) with Imidazole

Theoretical Studies on the 1,2-Cycloaddition Reaction of Singlet Molecular Oxygen (<sup>1</sup>O<SUB>2</SUB>) with Imidazole

Physical quenching and chemical reaction of singlet molecular oxygen with azo dyes [Erratum to document cited in CA110(8):59512m

ADVERTISEMENT RETURN TO ISSUEPREVArticlePhysical quenching and chemical reaction of singlet molecular oxygen with azo dyes [Erratum to document cited in CA110(8):59512m]Pietro Bortolus, Sandra Monti, Angelo Albini, Elisa Fasani, and Silvio PietraCite this: J. Org. Chem. 1989, 54, 13, 3246Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://doi.org/10.1021/jo00274a071RIGHTS & PERMISSIONSArticle Views42Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (94 KB) Get e-Alerts Get e-Alerts