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Oxidative modifications of amino acid side chains in proteins are a hallmark of oxidative stress, and they are usually regarded as structural damage. However, amino acid oxidation may also have a protective effect and may serve regulatory or structural purposes. Here, we have attempted to characterize the global redox role of the 20 proteinogenic amino acids in animals by analyzing their usage frequency in 5 plausible evolutionary paradigms of increased oxidative burden: (i) peroxisomal proteins versus all proteins, (ii) mitochondrial proteins versus all proteins, (iii) mitochondrially encoded respiratory chain proteins versus all mitochondrial proteins, (iv) proteins from long-lived animals versus those from short-lived animals, and (v) proteins from aerobic, free-living animals versus those from facultatively anaerobic animals. We have found that avoidance of cysteine in the oxidative condition was the most pronounced and significant variation in the majority of comparisons. Beyond this preeminent pattern, only local signals were observed, primarily increases in methionine and glutamine as well as decreases in serine and proline. Hence, certain types of cysteine oxidation appear to enforce its proteome-wide evolutionary avoidance despite its essential role in disulfide bond formation and metal ligation. The susceptibility to oxidation of all other amino acids appears to be generally unproblematic, and sometimes advantageous. [ABSTRACT FROM AUTHOR]

We examined the reaction of hydroxyl radicals (HO•) and sulfate radical anions (SO4•−), which is generated by ionizing radiation in aqueous solutions under anoxic conditions, with an alternating GC doubled-stranded oligodeoxynucleotide (ds-ODN), i.e., the palindromic 5′-d(GCGCGC)-3′. In particular, the optical spectra of the intermediate species and associated kinetic data in the range of ns to ms were obtained via pulse radiolysis. Computational studies by means of density functional theory (DFT) for structural and time-dependent DFT for spectroscopic features were performed on 5′-d(GCGC)-3′. Comprehensively, our results suggest the addition of HO• to the G:C pair moiety, affording the [8-HO-G:C]• detectable adduct. The previous reported spectra of one-electron oxidation of a variety of ds-ODN were assigned to [G(-H+):C]• after deprotonation. Regarding 5′-d(GCGCGC)-3′ ds-ODN, the spectrum at 800 ns has a completely different spectral shape and kinetic behavior. By means of calculations, we assigned the species to [G:C/C:G]•+, in which the electron hole is predicted to be delocalized on the two stacked base pairs. This transient species was further hydrated to afford the [8-HO-G:C]• detectable adduct. These remarkable findings suggest that the double-stranded alternating GC sequences allow for a new type of electron hole stabilization via delocalization over the whole sequence or part of it. [ABSTRACT FROM AUTHOR]

Oxidative modifications of amino acid side chains in proteins are a hallmark of oxidative stress, and they are usually regarded as structural damage. However, amino acid oxidation may also have a protective effect and may serve regulatory or structural purposes. Here, we have attempted to characterize the global redox role of the 20 proteinogenic amino acids in animals by analyzing their usage frequency in 5 plausible evolutionary paradigms of increased oxidative burden: (i) peroxisomal proteins versus all proteins, (ii) mitochondrial proteins versus all proteins, (iii) mitochondrially encoded respiratory chain proteins versus all mitochondrial proteins, (iv) proteins from long-lived animals versus those from short-lived animals, and (v) proteins from aerobic, free-living animals versus those from facultatively anaerobic animals. We have found that avoidance of cysteine in the oxidative condition was the most pronounced and significant variation in the majority of comparisons. Beyond this preeminent pattern, only local signals were observed, primarily increases in methionine and glutamine as well as decreases in serine and proline. Hence, certain types of cysteine oxidation appear to enforce its proteome-wide evolutionary avoidance despite its essential role in disulfide bond formation and metal ligation. The susceptibility to oxidation of all other amino acids appears to be generally unproblematic, and sometimes advantageous.

A cyclic alkyl(amino)carbene (CAAC)-stabilized dicoordinate aminoborylene is synthesized by the twofold reduction of a [(CAAC)BCl2 (TMP)] (TMP=2,6-tetramethylpiperidyl) precursor. NMR-spectroscopic, X-ray crystallographic and computational analyses confirm the cumulenic nature of the central C=B=N moiety. Irradiation of [(CAAC)B(TMP)] (2) resulted in an intramolecular C-C bond activation, leading to a doubly-fused C10 BN heterocycle, while the reaction with acetonitrile resulted in an aryl migration from the CAAC to the acetonitrile nitrogen atom, concomitant with tautomerization of the latter to a boron-bound allylamino ligand. One-electron oxidation of 2 with CuX (X=Cl, Br) afforded the corresponding amino(halo)boryl radicals, which were characterized by EPR spectroscopy and DFT calculations. Placing 2 under an atmosphere of CO afforded the tricoordinate (CAAC,CO)-stabilized aminoborylene. Finally, the twofold oxidation of 2 with chalcogens led, in the case of N2O and sulfur, to the splitting of the B-CCAAC bond and formation of the 2,4-diamino-1,3,2,4-dichalcogenadiboretanes and CAAC-chalcogen adducts, whereas with selenium a monomeric boraselenone was isolated, which showed some degree of B-Se multiple bonding. [ABSTRACT FROM AUTHOR]

Amine oxidation is an important organic reaction for the production of high-value N-containing compounds. However, it is still challenging to control the reactivity of active N-centered radicals to selectively access N-oxidation products. Herein, this study reports the engineering of cytochrome P450BM3 into multifunctional N-oxidizing enzymes with the assistance of dual-functional small molecules (DFSM) to selectively produce N-oxygenation (i.e., p-nitrosobenzene, p-nitrobenzene, and azoxybenzene) and one-electron oxidation products (i.e., oligomeric quinones and azobenzene) from aromatic amines. The best mutant, F87A/T268V/V78T/A82T, exclusively gives p-nitrosobenzene (up to 98% selectivity), whereas the selectivity for p-nitrobenzene is >99% using the mutant F87A/T268V/A82T/I263L. Crystal structure analysis reveals that key mutations and DFSM exert synergistic effects on catalytic promiscuity by controlling the substrate orientation in active center. This study highlights the potential of DFSM-facilitated P450 peroxygenase and peroxidase for the synthesis of N-containing compounds via the controllable oxidation of aromatic amines, substantially expanding the chemical space of P450 enzymes., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

New complex of low-valent germanium PhenoxAPGe (I) based on the redox-active ligand 2,4,6,8-tetra-tert-butylphenoxazin-1-one is synthesized and structurally characterized. Its versatile reactivity is demonstrated for the acid-base and redox transformations. The reaction of germylene I with Ni(COD)2 is found to result in the substitution of both cyclooctadiene molecules, coordination of four germylene fragments to zero-valent nickel, and formation of compound (PhenoxAPGe)4Ni (II). The reaction of compound I with [CpNi(CO)]2 in a toluene solution affords complex (PhenoxAPGe)2(NiCp)2 (III), being the substitution product of two carbonyl groups by two isolobal germylene fragments. The reaction with the one-electron oxidant (3,6-di-tert-butyl-2-methoxyphenoxyl radical) generates labile paramagnetic germylene IV characterized by EPR spectroscopy. Digermylene oxide V synthesized by the hydrolysis of the starting germylene Iin situ reacts with N-heterocyclic carbene and KC8 to form ionic derivatives VI and VII containing the Ge(II)–O–Ge(II) fragment. Germylene I is tested as a catalyst for the hydroboration of benzaldehyde. The molecular structures of the compounds are determined by X-ray diffraction (СIF files CCDC nos. 2117783 (I), 2124277 (II), 2125357 (III), and 2118393 (VII)). [ABSTRACT FROM AUTHOR]

Multiple steps are needed to achieve the C−H functional of aromatic aldehyde, since the C−H functional reaction usually occurs preferentially at the aldehydic C−H bond over the aryl C−H bond. We report an efficient azidation method mediated by dirhodium(II) catalysts to achieve the direct aryl azidation of aromatic aldehydes avoiding the simultaneous use of protected aldehydes and prefunctionalized arenes. The regioselectivity of this method is similar to those of typical aromatic electrophilic substitution reactions. The resulting azidobenzaldehyde products are versatile building blocks or precursors for the synthesis of many biologically active compounds. The mechanism studies indicate that the one‐electron oxidative intermediate Rh2(II,III)N3 is responsible for the azide transfer. [ABSTRACT FROM AUTHOR]

The widely used antimalarial drug amodiaquine (AQ) contains a 7-Cl-quinoline unit, a substituted 4-aminophenol part connected through the amino group and a tertiary amine part. The 4-aminophenol unit can be easily oxidized through radical intermediates to iminoquinone. This reaction also takes place in vitro and in vivo enzymatic reactions. The reaction is expected to have an important role in degradation of AQ in surface waters and also during degradation in advanced oxidation processes. In this paper by means of radiation chemical techniques the one-electron oxidation and reduction of AQ were studied using transient kinetics, kinetics of AQ degradation, formation and decay of end-products of radical reactions. The hydroxyl radicals were shown to add both to the quinoline (∼ 38%) and aminophenol (∼ 50%) parts via formation of hydroxycyclohexadienyl radicals and by H-abstraction or by an electron removal from the tertiary amine part of the molecule (∼ 12%). The dihydroxycyclohexadienyl radical formed on the aminophenol part is suggested to transform to aminophenoxy radical. The hydrated electrons can also effectively contribute to AQ degradation. Chemical oxygen demand and total organic carbon content investigations were also made in order to characterize the ionizing radiation-induced oxidation and mineralization. In aerated 0.1 mmol dm−3 solution, at 2.5 kGy absorbed dose AQ and its higher molecular mass degradation products demolished completely. Ionizing irradiation is a capable technique for degradation of AQ under both oxidative and reductive circumstances. [ABSTRACT FROM AUTHOR]

Oxidation is one of the deterioration reactions of proteins in food, the importance of which is comparable to others such as Maillard, lipation, or protein‐phenol reactions. While research on protein oxidation has led to a precise understanding of the processes and consequences in physiological systems, knowledge about the specific effects of protein oxidation in food or the role of "oxidized" dietary protein for the human body is comparatively scarce. Food protein oxidation can occur during the whole processing axis, from primary production to intestinal digestion. The present review summarizes the current knowledge and mechanisms of food protein oxidation from a chemical, technological, and nutritional–physiological viewpoint and gives a comprehensive classification of the individual reactions. Different analytical approaches are compared, and the relationship between oxidation of food proteins and oxidative stress in vivo is critically evaluated. [ABSTRACT FROM AUTHOR]

The synthesis and X‐ray structure of a new manganese(V) mesitylimido complex with a tetraamido macrocyclic ligand (TAML), [MnV(TAML)(N‐Mes)]− (1), are reported. Compound 1 is oxidized by [(p‐BrC6H4)3N]+.[SbCl6]− and the resulting MnVI species readily undergoes H‐atom transfer and nitrene transfer reactions. [ABSTRACT FROM AUTHOR]

New stannylene AdAPSn (I) based on 4,6-di-tert-butyl-N-adamantyl-o-aminophenol is synthesized and structurally characterized. Stannylene I in the crystalline state forms infinite chains due to intermolecular donor–acceptor Sn–N and metallophilic Sn···Sn interactions. The reactivities of compound I and earlier synthesized t-BuAPSn (II) are studied using their redox and acid–base reactions. Stannylenes I and II are inserted at the S–S bond of tetramethylthiuram disulfide to form the corresponding tin(IV) dithiocarbamate complexes. The reactions with soft one-electron oxidants involve the redox-active o-amidophenolate ligand and generate labile paramagnetic stannylenes studied by EPR spectroscopy. The presence of a lone electron pair at the low-valence tin atom is a reason for its basic properties, which is demonstrated for the reaction of compound I with nanocarbonyl iron. The structures of selected synthesized compounds are determined by X-ray diffraction analysis (СIF files CCDC nos. 1905419–1905421). [ABSTRACT FROM AUTHOR]

Laser flash photolysis and high-resolution mass spectrometry were used to investigate the mechanism of one-electron oxidation of two S-alkylglutathiones using 3-carboxybenzophenone (3CB) as a photosensitizer. This report indicates an unexpected reaction pathway of the α-aminoalkyl radical cation (αN+) derived from the oxidation of S-alkylglutathiones. Instead of a common hydrolysis reaction of αN+ reported earlier for methionine and other sulfur-containing aminoacids and peptides, an intramolecular ring-closure reaction was found for S-alkylglutathiones.

Proteins are main targets of oxidants in biological systems. This oxidation may occur in the protein backbone as well as in certain amino acid side chains, depending on the oxidant and amino acid intrinsic reactivity. Moreover, many enzymes are capable of generating stable amino acid radicals, such as tyrosyl, tryptophanyl and cysteinyl radicals. These species react very rapidly (many times as diffusion-controlled reactions) with relevant cellular open-shell species such as nitric oxide (·NO) or molecular oxygen (O2). The exception to this apparent rule is tyrosyl radical, that reacts at diffusion rates with ·NO, but shows very slow reactivity towards O2 (rate constant <103 M−1 s−1). In this work, we provide a comparative molecular-level description of the reaction mechanisms involved in the reactions of tyrosyl, tryptophanyl and cysteinyl radicals towards ·NO and O2, through quantum mechanics simulations which allow us to obtain relevant energetic and structural parameters, proposing a molecular explanation to this tyrosyl discrimination capability, namely, its marginal reactivity with O2. [ABSTRACT FROM AUTHOR]

Abstract: One‐electron oxidation of 1,4,2,5‐diazadiborinine 1 has been studied. While the reaction of 1 a bearing phenyl groups on the B atoms with AgAl{OC(CF3)3}4 afforded a complex mixture, the same oxidation reaction with 1 b featuring bulky mesityl substituents on the B atoms rendered the corresponding cation radical 2 b as an isolable species. X‐ray diffraction analysis, EPR spectroscopy, and DFT calculations of 2 b revealed the delocalization of the unpaired electron over the entire π‐system of 2 b, as well as a large spin density (0.76 in total) on the two equivalent boron atoms. The chemical trapping reaction of 2 b with p‐benzoquinone and triphenyltin hydride afforded the dicationic species 3 containing two newly formed B−O bonds and the monocationic product 2b‐H containing a B−H bond, respectively, thus confirming the boron‐centered radical reactivity of 2 b. [ABSTRACT FROM AUTHOR]

One electron transfer oxidation has long been proposed as a route to the ultimate electrophilic and carcinogenic metabolites of both methylated and non-methylated polycyclic aromatic hydrocarbons (PAH). The carcinogenic hydrocarbon 3-methylcholanthrene (3-MC) has a methyl-analogous function at its meso-anthracenic center in the form of a dimethylene bridge, and treatment of this compound with the one electron transfer oxidizing reagent ferric ferricyanide, Fe III (Fe III (CN) 6 ), in mixed aqueous-organic media generated multiple oxygenated species, many of which duplicate those found in mammalian metabolism including known carcinogens 1-hydroxy-3MC and 1-keto-3MC. These results are in agreement with a Unified Theory for PAH Carcinogenicity which predicts in vivo generation of a proximate benzylic alcohol metabolite from the 3-MC procarcinogen and conjugation with a moiety such as sulfate intended for rapid urinary excretion. The sulfate instead acts as a leaving group and generates an electrophilic carbocation capable of reacting with sensitive nucleophiles such as DNA in cellular nuclei. The products of one electron transfer oxidation align well with predictions of the Unified Theory since in many cases these products provide substrates or precursors for conjugation reactions. [ABSTRACT FROM AUTHOR]

Oxidation by OH radicals produced by γ -radiolysis of single amino acids proline and glutamic acid accompanied by a series of Met-containing model peptides were investigated by a combined study of tandem mass spectrometry and infrared multiple-photon dissociation spectroscopy in the fingerprint region. The thioether group of methionine has been identified as a common target of OH free radicals leading to a S+ radical cation, which made a 2-center-three electron (2c-3e) bond with any atom having having a lone pair of electrons. However, the final fate of these 2c-3e free radicals is still unknown. These studies led to the identification of the final stable products of oxidation and the localization of the modified sites. We show that the final products contain mostly methionine sulfoxide, whatever the structure of the preceding free radical. Although the distance between two Met residues controls the nature of free radicals formed in the peptides, it has no significant effect on the final products of oxidation. These results thus confirm that the final products are not controlled by free radical structure. Also, although no proline free radical was detected previously, we show that proline residue can be oxidized. [Display omitted] • Methionine as a common target of the reactive oxygen species (ROS). • Neighboring group effect on peptide oxidation. • Effect of the free radical structure on the final products of oxidation. • IRMPD Spectroscopy as an analytical tool to identify the oxidation products. [ABSTRACT FROM AUTHOR]

This mini-review focuses on the recent identification of several novel radiation-induced single and tandem modifications in cellular DNA. For this purpose accurate high-performance electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was applied allowing their quantitative measurement and unambiguous characterization. Exposure of human cells to gamma rays led to the formation of several modified bases arising from the rearrangement of the pyrimidine ring of thymine, cytosine and 5-methylcytosine subsequent to initial addition of an hydroxyl radical ( • OH) to the 5,6-ethylenic bond. In addition, 5-hydroxymethylcytosine, an novel epigenetic mark, and 5-formylcytosine, were found to be generated consecutively to • OH-mediated hydrogen abstraction from the methyl group of 5-methylcytosine. Relevant mechanistic information on one-oxidation reactions of cellular DNA was also gained from the detection of 5-hydroxycytosine and guanine-thymine intra-strand adducts whose formation is rationalized by the generation of related base radical cation. Attempts to search for the radiation-induced formation of purine 5′,8-cyclo-2′-deoxyribonucleosides were unsuccessful with the exception of trace amounts of (5′ S )-5′,8-cyclo-2′-deoxyadenosine. [ABSTRACT FROM AUTHOR]

We report the synthesis of a series of ruthenium complexes supported by the phosphine olefin ligand tropPPh2 (trop=5-H-dibenzo-[a,d]cyclohepten-5-yl) in the oxidation states 0, +I, and +II, formed via successive one-electron oxidization steps from Ru0(tropPPh2)2. The bidentate character of the tropPPh2 ligand and its steric hindrance force the complexes to adopt uncommon geometries, which were investigated by X-ray diffraction analysis. EPR data of the mononuclear RuI complex reveal couplings of the unpaired spin with the ruthenium and two phosphorus nuclei, as well as the olefinic protons which show that the spin is mainly localized on the RuI center. [ABSTRACT FROM AUTHOR]

We report the synthesis of a series of ruthenium complexes supported by the phosphine olefin ligand tropPPh2 (trop=5-H-dibenzo-[a,d]cyclohepten-5-yl) in the oxidation states 0, +I, and +II, formed via successive one-electron oxidization steps from Ru0(tropPPh2)2. The bidentate character of the tropPPh2 ligand and its steric hindrance force the complexes to adopt uncommon geometries, which were investigated by X-ray diffraction analysis. EPR data of the mononuclear RuI complex reveal couplings of the unpaired spin with the ruthenium and two phosphorus nuclei, as well as the olefinic protons which show that the spin is mainly localized on the RuI center. [ABSTRACT FROM AUTHOR]

Substantial conversion of nitrophenols, typical high-redox potential phenolic substrates, by heme peroxidases has only been reported for lignin peroxidase (LiP) so far. But also a dye-decolorizing peroxidase of Auricularia auricula-judae ( Aau DyP) was found to be capable of acting on (i) ortho -nitrophenol ( o NP), (ii) meta -nitrophenol ( m NP) and (iii) para -nitrophenol ( p NP). The pH dependency for p NP oxidation showed an optimum at pH 4.5, which is typical for phenol conversion by DyPs and other heme peroxidases. In the case of o NP and p NP conversion, dinitrophenols (2,4-DNP and 2,6-DNP) were identified as products and for p NP additionally p -benzoquinone. Moreover, indications were found for the formation of random polymerization products originating from initially formed phenoxy radical intermediates. Nitration was examined using 15 N-labeled p NP and Na 14 NO 2 as an additional source of nitro-groups. Products were identified by HPLC–MS, and mass-to-charge ratios were evaluated to clarify the origin of nitro-groups. The additional nitrogen in DNPs formed during enzymatic conversion was found to originate both from 15 N- p NP and 14 NO 2 Na. Based on these results, a hypothetical reaction scheme and a catalytically responsible confine of the enzyme’s active site are postulated. [ABSTRACT FROM AUTHOR]

Background The recent growth in knowledge of free radicals in biology is producing a medical revolution that promises a new age in health and disease management. In the last two decades there has been an explosive interest in the role of oxygen free radicals, more generally known as “reactive oxygen species” and of “reactive nitrogen species” in experimental and clinical medicine. Methods The flowering top extract of Hypericum mysorense possessing potent anti-oxidant activity was subjected to bio-active guided isolation. Pulse radiolysis technique was used to determine the transient spectrum and rate constant for the one-electron oxidation of hyperoside by O H , N 3 , NO 2 , NO , CCl 3 OO radicals in aqueous solution. Results Three compounds were isolated and characterized as rutin, quercetin-3- O -galactoside (hyperoside) and quercetin from spectral analysis. The hyperoside radical showed pK a1 and pK a2 at 5.4 and 9.2. Both, Cu(II) and iron(II) ions form chelate with hyperoside. The Cu–hyperoside chelate was able to scavenge O 2 − , k= 7.0(±0.3)×10 6 dm 3 mol −1 s −1 at pH 9. The repair rates for tryptophan and guanosine radicals by hyperoside were also determined. Conclusion The reduction potential of hyperoside radical was determined by cyclic voltammetric and pulse radiolysis methods. [ABSTRACT FROM AUTHOR]

Dimethyl palladium(II) complexes with various bi- and tri-dentate ligands, (L 2 )Pd II (CH 3 ) 2 , react readily with the one-electron oxidant ferrocenium hexafluorophosphate (Fc + ) in acetone- d 6 . These oxidations typically proceed by one of two pathways. Oxidatively-induced methyl transfer forms trimethyl palladium(IV) intermediates which usually undergo reductive C−C coupling and form ethane. Alternatively, oxidation can cause Pd–C bond homolysis, which yields predominantly methane and methylferrocene, a product of methyl radical trapping. The reaction selectivity is dependent on ligand identity and likely due to the ability of different classes of ligands to stabilize intermediates in the Pd IV oxidation state. Complexes containing the bidentate diimine ligands 1,10-phenanthroline (phen) or 2,3-dimethyl-1,4-di-4-tolyl-1,4-diazabuta-1,3-diene (Tol 2 DAB) adhere to the ethane producing pathway previously reported for ( t Bu 2 bpy)Pd(CH 3 ) 2 ( t Bu 2 bpy = 4,4′-bis( tert -butyl)-2,2′-bipyridine), as does the complex of the potentially tridentate 6-methyl- N , N ′- bis -2-pyridinyl-2-pyridinamine ligand. In contrast, Fc + oxidations of complexes with bis-carbene (1,1′-methylene-3,3′-tert-butyldiimidazole-2,2′-diylidene, tBu CC tBu ), bis-phosphine ( tert -butyl-bis(diphenylphosphinomethyl)amine ( t BuN(CH 2 PPh 2 ) 2 , PCNCP), or tris(pyrazolyl)methane ligands resulted in little or no ethane production. These reactions likely involve either methyl radicals or trimethyl Pd IV complexes that are stable towards C−C reductive elimination. Oxidation of (TMEDA)Pd(CH 3 ) 2 (TMEDA = ( N , N , N ′, N ′-tetramethylethylenediamine) yields both methane and ethane, suggesting that both Pd–C bond homolysis and oxidative methyl transfer are competitive in this case. [ABSTRACT FROM AUTHOR]

Purpose: To study the formation and subsequent reactions of the 5-methyl-2'-deoxycytidine cation radical (5-Me-2'-dC⋅+) in nucleosides and DNA-oligomers and compare to one-electron oxidized thymidine. Materials and methods: Employing electron spin resonance (ESR), cation radical formation and its reactions were investigated in 5-Me-2'-dC, thymidine (Thd) and their derivatives, in fully double-stranded (ds) d[GC*GC*GC*GC*]2 and in the 5-Me-C/A mismatched, d[GGAC*AAGC:CCTAATCG]2, where C* = 5-Me-C. Results: We report S-Me-l'-dC⋅+ production by one-electron oxidation of 5-Me-2'-dC by Cl2⋅- via annealing in the dark at 155 K. Progressive annealing of 5-Me-2'-dC⋅+ at 155 K produces the allylic radical (C-CH2⋅-. However, photoexcitation of 5-Me-2'-dC⋅+ by 405 nm laser or by photoflood lamp leads to only C3'⋅ formation. Photoexcitation of N3-deprotonated thyminyl radical in Thd and its 5'-nucleotides leads to C3'⋅ formation but not in 3'-TMP which resulted in the allylic radical (U-CH2⋅) and C5'⋅ production. For excited 5-Me-2',3'-ddC⋅+, absence of the 3'-OH group does not prevent C3⋅ formation. For d[GC*GC*GC*GC*]2 and d[GGAC*AAGC:CCTAATCG], intra-base paired proton transferred form of G cation radical (G(N1-H) ⋅: C(+ H+)) is found with no observable 5-Me-2'-dC⋅+ formation. Photoexcitation of (G(N1-H) ⋅:C(-1- H+)) in d[GC*GC*GC*GC*]2 produced only C1'⋅ and not the expected photoproducts from 5-Me-2'-dC⋅+. However, photoexcitation of (G(N1-H) ⋅:C (+ H+)) in d[GGAC*AAGC:CCTAATCG] led to C5'⋅ and C1'⋅ formation. Conclusions: C-CH2⋅ formation from 5-Me-2'-dC⋅+ occurs via ground state deprotonation from C5-methyl group on the base. In the excited 5-Me-2'-dC⋅+ and 5-Me-2',3'-ddC⋅+, spin and charge localization at C3' followed by deprotonation leads to C3'⋅ formation. Thus, deprotonation from C3' in the excited cat- ion radical is kinetically controlled and sugar C-H bond energies are not the only controlling factors in these deprotonations. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this survey is to critically review the available information on one-electron oxidation reactions of nucleobases in cellular DNA with emphasis on damage induced through the transient generation of purine and pyrimidine radical cations. Since the indirect effect of ionizing radiation mediated by hydroxyl radical is predominant in cells, efforts have been made to selectively ionize bases using suitable one-electron oxidants that consist among others of high intensity UVC laser pulses. Thus, the main oxidation product in cellular DNA was found to be 8-oxo-7,8-dihydroguanine as a result of direct bi-photonic ionization of guanine bases and indirect formation of guanine radical cations through hole transfer reactions from other base radical cations. The formation of 8-oxo-7,8-dihydroguanine and other purine and pyrimidine degradation products was rationalized in terms of the initial generation of related radical cations followed by either hydration or deprotonation reactions in agreement with mechanistic pathways inferred from detailed mechanistic studies. The guanine radical cation has been shown to be implicated in three other nucleophilic additions that give rise to DNA-protein and DNA-DNA cross-links in model systems. Evidence was recently provided for the occurrence of these three reactions in cellular DNA. Conclusion: There is growing evidence that one-electron oxidation reactions of nucleobases whose mechanisms have been characterized in model studies involving aqueous solutions take place in a similar way in cells. It may also be pointed out that the above cross-linked lesions are only produced from the guanine radical cation and may be considered as diagnostic products of the direct effect of ionizing radiation. [ABSTRACT FROM AUTHOR]

The oxidation of a NiII complex bearing a tetradentate phosphasalen ligand, which differs from salen by the presence of an iminophosphorane (PN) in place of an imine unit, was easily achieved by addition of a silver salt. The site of this oxidation was investigated with a combination of techniques (NMR, EPR, UV/Vis spectroscopy, X-ray diffraction, magnetic measurements) as well as DFT calculations. All data are in agreement with a high-valent NiIII center concentrating the spin density. This markedly differs from precedents in the salen series for which oxidation on the metal was only observed at low temperature or in the presence of additional ligands or anions. Therefore, thanks to the good electron-donating properties of the phosphasalen ligand, [Ni(Psalen)]+ represents a rare example of a tetracoordinated high-valent nickel complex in presence of a phenoxide ligand. [ABSTRACT FROM AUTHOR]

Abstract: The method of radiolysis is based upon the interaction of ionising radiation with the solvent (water). One can form the same free radicals as in conditions of oxidative stress (•OH, O2 • –, NO2 •…). Moreover, the quantity of reactive oxygen (ROS) or nitrogen (RNS) species formed in the irradiated medium can be calculated knowing the dose and the radiation chemical yield, G, thus this method is quantitative. The use of the method of radiolysis has provided a wealth of data, especially about the kinetics of the oxidation by various free radicals and their mechanisms, the identification of transients formed, their lifetimes and the possibility to repair them by the so-called antioxidants. In this review we have collected the most recent data about protein oxidation that might be useful to a proteomic approach. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine. [Copyright &y& Elsevier]

Quantum-chemical calculations {DFT(B3LYP)/6-311+G(d,p)} were performed for all possible tautomers (aromatic and nonaromatic) of neutral 2- and 4-aminopyridines and their oxidized and reduced forms. One-electron oxidation has no important effect on the tautomeric preference for 2-aminopyridine. The amine tautomer is favored. However, oxidation increases the stability of the imine NH tautomer, and its contribution in the tautomeric mixture cannot be neglected. In the case of 4-aminopyridine, one-electron oxidation increases the stability of both the amine and imine NH tautomers. Consequently, they possess very close energies. As major tautomers, they dictate the composition of the tautomeric mixture. The CH tautomers may be considered as very rare forms for both neutral and oxidized aminopyridines. A reverse situation takes place for the reduced forms of aminopyridines. One-electron reduction favors the C3 atom for the labile proton for both aminopyridines. This may partially explain the origin of the CH tautomers for the anionic states of nucleobases containing the exo NH group. [ABSTRACT FROM AUTHOR]

Abstract: Consequences of one-electron oxidation and one-electron reduction were studied for imidazole (I) in the gas phase and in water (apolar and polar environment, respectively) using quantum-chemical methods {DFT(B3LYP)/6-311+G**, G2, G2(MP2), G3B3, and PCM//B3LYP/6-311+G(d,p)}. For calculations, all possible prototropic tautomers (NH and CH) were considered for the neutral and redox forms of I. Independently on environment (gas phase or water), an interesting change of the composition of the tautomeric mixture takes place when going from the neutral to reduced form of imidazole. One-electron reduction (I+e→I− ) increases stability of the CH tautomers (non-aromatic forms). On the other hand, one-electron oxidation (I−e→I+ ) has no important effect on the tautomeric preferences. The NH tautomers predominate for both neutral (I) and oxidized imidazole (I+ ). For the favored forms in the gas phase, the oxidation Gibbs energy is close to 200kcalmol−1, and the reduction Gibbs energy is more than ten times lower. In water, these energies are lower by more than 50kcalmol−1. Independently on the state of oxidation, π-electrons are more delocalized for the NH than CH tautomers. [Copyright &y& Elsevier]

Oxidation of Li/X phosphinidenoid complex 2, obtained via selective deprotonation from the P-H precursor 1, with [Ph3C]BF4 led to the formation of two P-F substituted diorganophosphane complexes 6, 7; the latter tautomer 7 formed via H-shift from 6. In contrast, oxidation of 2 with [( p-Tol)3C]BF4 led to three major and one minor intermediates at low temperature, which we tentatively assign to two pairs of P-C atropisomers 10 a, a′ and 10 c, c′ and which differ by the relative orientations of their CH(SiMe3)2 and W(CO)5 groups. Conversion of all isomers led finally to complex 11 having a ligand with a long PC bond to the central trityl* carbon atom, firmly established by single-crystal X-ray analysis. DFT calculations at the B3LYP/def2-TZVPP//BP86/def2-TZVP level of theory on real molecular entities revealed the structures of the in situ formed combined singlet diradicals ( 4+ 5 and 5+ 9) and the nature of intermediates on the way to the final product, complex 11. Remarkable is that all isomers of 11 possess relative energies in the narrow energy regime of about 20 kcal mol−1. A preliminary study revealed that complex 11 undergoes selective PC bond cleavage at 75 °C in toluene solution. [ABSTRACT FROM AUTHOR]

Abstract: Tricyclic antidepressants (TCAs), along with phenothyazines and some industrial chemicals, are shown to react with enzymes that exhibit peroxidase activity. These reactions result in the formation of reactive intermediates having unpaired electrons. The peroxidase oxidation and reactivity of two TCAs, desipramine and clomipramine, were investigated. As a model of peroxidase, horseradish peroxidase (HRP) was employed. The products of the peroxidase catalyzed oxidation of desipramine and clomipramine were identified as N-dealkylated compounds iminodibenzyl and 3-chloroiminodibenzyl using the GC/MS technique. Both drugs formed broad UV/vis absorption spectra in the presence of HRP and H2O2, indicating the formation of a radical cations—reactive intermediate of the oxidation reaction. The dynamics of the formation of the desipramine intermediate was studied using UV/vis spectroscopy. The extinction coefficient was measured for the reactive intermediate, 7.80×103 M−1 cm−1, as well as the apparent Michaelis–Menten and catalytic constants, 4.4mM and 2.3s−1, respectively. Both desipramine and clomipramine degraded DNA in the presence of HRP/H2O2, as was revealed by agarose gel electrophoresis and PCI extraction. Manipulating the kinetic parameters of drug’s radical formation and determining the extent of degradation to biomolecules could be potentially used for designing effective agents exhibiting specific reactivity. [Copyright &y& Elsevier]

Quantum-chemical calculations were performed for all possible isomers of neutral aniline and its redox forms, and intramolecular proton-transfer (prototropy) accompanied by π-electron delocalization was analyzed. One-electron oxidation (PhNH - e → [PhNH]) has no important effect on tautomeric preferences. The enamine tautomer is preferred for oxidized aniline similarly as for the neutral molecule. Dramatical changes take place when proceeding from neutral to reduced aniline. One-electron reduction (PhNH + e → [PhNH]) favors the imine tautomer. Independently on the state of oxidation, π- and n-electrons are more delocalized for the enamine than imine tautomers. The change of the tautomeric preferences for reduced aniline may partially explain the origin of the CH tautomers for reduced nucleobases (cytosine, adenine, and guanine). [ABSTRACT FROM AUTHOR]

Oxidation of essentially pure intermediate-spin iron(III) porphyrinates such as ruffled Fe(TiPrP)ClO4 and saddled Fe(OETPP)ClO4 produces the corresponding six-coordinate iron(III) porphyrin(por) radical cations [Fe(Por)(ClO4)2], where TiPrP and OETPP are dianions of 5,10,15,20-tetraisopropylporphyrin and 2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetraphenylporphyrin, respectively. Spin–spin interactions in these complexes are very much different; while ruffled [Fe(TiPrP)(ClO4)2] exhibits no antiferromagnetic coupling, saddled [Fe(OETPP)(ClO4)2] does exhibit it. The difference in magnetic behaviors has been explained in terms of the deformation mode and electron configuration of these complexes. [Copyright &y& Elsevier]

Abstract: Change of the tautomeric preference was observed at the DFT(B3LYP)/6-311+G(d,p) level when proceeding from neutral to reduced phenol. One-electron reduction (PhOH+e→[PhOH]− ) favors the keto tautomer (2,4-cyclohexadienone). On the other hand, one electron oxidation (PhOH−e→[PhOH]+ ) has no important effect on the tautomeric preference. The enol tautomer is preferred for oxidized phenol, similarly as for the neutral molecule. Independently on the state of oxidation, π-electrons are more delocalized for the enol tautomer than for the keto ones. Aromaticity dictates the tautomeric preference solely for the neutral and oxidized forms. [ABSTRACT FROM AUTHOR]

Abstract: Neutrophils play a major role in acute inflammation in part by generating superoxide and an array of other reactive species. These white blood cells also contribute to protection against inflammatory pain by releasing opioid peptides. The biochemical interactions of enkephalins with neutrophil-derived oxidants are not well understood. In this investigation we reveal that neutrophils use myeloperoxidase to oxidize enkephalins to their corresponding tyrosyl free radicals, which react preferentially with the superoxide to form a hydroperoxide. In methionine enkephalin, rapid intramolecular oxygen transfer from the hydroperoxide to the Met sulfur results in the formation of a sulfoxide derivative. This reaction may occur at sites of inflammation where enkephalins are released and neutrophils generate large amounts of superoxide. Hydroperoxide formation destroys the aromatic character of the Tyr residue by forming a bicyclic structure via conjugate addition of the terminal amine to the phenol ring. As the N-terminal Tyr and its amino group are essential for their opiate activity, we hypothesize that oxidative modification of this residue should affect the analgesic activity of enkephalins. [Copyright &y& Elsevier]

Abstract: One or more of the muconaldehyde isomers is a putative product of benzene metabolism. As muconaldehydes are highly reactive dienals and potentially mutagenic they might be relevant to the carcinogenicity of benzene. Muconaldehydes may be derived through the action of a cytochrome P450 mono-oxygenase on benzene oxide–oxepin, which are established metabolites of benzene. Oxidation of benzene oxide–oxepin either by the one-electron oxidant cerium(IV) ammonium nitrate (CAN) or by iron(III) tris(1,10-phenanthroline) hexafluorophosphate in acetone at −78°C or acetonitrile at −40°C gave (E,Z)-muconaldehyde, which was a single diastereoisomer according to analysis by 1H NMR spectroscopy. Reaction of toluene-1,2-oxide/2-methyloxepin with CAN gave (2E,4Z)-6-oxo-hepta-2,4-dienal. Similarly, the action of CAN on 1,6-dimethylbenzene oxide-2,7-dimethyloxepin gave (3Z,5E)-octa-3,5-diene-2,7-dione. In vivo, benzene oxide–oxepin could suffer one-electron oxidation by cytochrome P450 mono-oxygenase giving (E,Z)-muconaldehyde. The observations presented may be relevant to the toxicology of benzene oxide–oxepin and other arene oxide–oxepins as we have previously shown that (E,Z)-muconaldehyde, analogously to (Z,Z)-muconaldehyde, affords pyrrole adducts with the exocyclic amino groups of the DNA bases adenine and guanine. Independent of their possible toxicological significance, the experiments described provide preparatively useful routes to (E,Z)-muconaldehyde and its congeners. Methods are also described for the trapping and analysis of reactive benzene metabolites, e.g. using the Diels–Alder reaction with the dienophile 4-phenyl-1,2,4-triazoline-3,5-dione to trap arene oxides and with the diene 1,3-diphenylisobenzofuran to trap enals. [Copyright &y& Elsevier]

This review describes the relationship between the NMR chemical shifts and electronic structures of one-electron oxidized products of iron(III) porphyrins such as iron(III) porphyrin radical cations or iron(IV) porphyrins. In the case of the former complexes, the iron(III) ions are classified into four types; (i) high-spin (S = 5/2), (ii) mixed high- and intermediate-spin (S = 5/2, 3/2), (iii) low-spin with the (dxy)2(dxz, dyz)3 ground state, and (iv) low-spin with the (dxz, dyz)4(dxy)1 ground state. In the case of the latter complexes, they mostly have FeIVO bonds. There is only one iron(IV) complex that has no FeIVO bond. The complexes classified as above exhibit unique NMR chemical shifts. Thus, the NMR spectroscopy serves a quite useful tool to determine the fine electronic structures of the one-electron oxidized iron(III) porphyrin complexes. [Copyright &y& Elsevier]

The competition between positions C1 and C3 in homoadamantane upon oxidation was studied both theoretically and experimentally. B3PW91 and MP2 calculations in the 6-31+G* basis were used to study the structure of the homoadamantane radical-cation and its complexes with acetonitrile. The reaction was found to proceed predominantly at the homoadamantane C1 position in the reaction with photoexcited 1,2,4,5-tetracyanobenzene. [ABSTRACT FROM AUTHOR]

Radical cations of three water-soluble organoselenium compounds, viz., selenourea, selenomethionine, and selenocystine, were produced and their reactions in the pH range 1–7 were studied using nanosecond pulse radiolysis technique. The radical cations, centered on the selenium atom, were generated by one-electron oxidation using hydroxyl (•OH) radicals and Cl2•− and Br2•− radicals. The radical cations of selenourea were converted to dimer radical cations in the entire pH range, which in presence of oxygen released elemental selenium as one of the products. The monomer radical cations of selenomethionine are stabilized at neutral pH by the lone pair of electrons on the N atom of the amino group and undergo partial decarboxylation to produce α-amino selenyl radicals, which are reducing in nature. At highly acidic conditions, when the lone pair is not available due to protonation, they were converted to dimer radical cations. Selenocystine, being a diselenide, produced monomer radical cations on one-electron oxidation in the entire pH range and acquires stability by sharing the electrons between the two adjacent selenium atoms. [Copyright &y& Elsevier]

Abstract: Centrins are calcium-binding proteins that play a significant role in the maintenance of the centrosomal organization, mainly in the continuity between centrosome and microtubular network. Recent data showed that centrosome duplication abnormalities, like overduplication for example, could be due to hydrogen peroxide, suggesting an important impact of oxidative stress. To challenge this hypothesis, we performed one-electron oxidation experiments with human centrin 2, starting from azide radicals. Our results first revealed several intermolecular cross-links generating dimers, tetramers, hexamers, and higher molecular mass species. Dimers result from covalent bond linking the C-terminal tyrosines of each monomer. Second, the methionyl residue at position 19 was oxidized on the monomeric centrin. Further, electron microscopy experiments on centrin 2 showed a preexisting hexameric organization that was stabilized by covalent bonds as a result of irradiation. Overall, these results show that centrin 2 is highly sensitive to ionizing radiation, which could have important consequences on its biological functions. [Copyright &y& Elsevier]

Abstract: The reaction of M(η6-1,3,5-Me3C6H3)2, M=Cr, Mo, with the tetrahalides of Groups 4 and 5 elements proceeds with the monoelectronic oxidation of the metal bis-arene to the [M(η6-Me3C6H3)2]+ cation. In the case of MX4, M=Ti, X=Cl, Br, M=V, X=Cl, and of Nb2Cl10 the reduction products are the titanium(III), vanadium(III) halides and the niobium(IV) chloride, isolated as the solvate anions [MCl4(THF)2]− and [NbCl4(CH3CN)]−. The reaction of the tetrachloro complexes MCl4(THF)2, M=Zr, Hf, with Cr(η6-1,3,5-Me3C6H3)2 in THF produces the ionic [Cr(η6-1,3,5-Me3C6H3)2][MCl5(THF)], which has been characterized by single-crystal X-ray diffraction in the case of hafnium. [Copyright &y& Elsevier]

Abstract: Hydroethidine (HE) is a cell-permeable probe used for the intracellular detection of superoxide. Here, we report the direct measurement of the rate constant between hydroethidine and superoxide radical anion using the pulse radiolysis technique. This reaction rate constant was calculated to be ca. 2×106 M−1 s−1 in water:ethanol (1:1) mixture. The spectral characteristics of the intermediates indicated that the one-electron oxidation product of HE was different from the one-electron reduction product of ethidium (E+). The HPLC-electrochemical measurements of incubation mixtures containing HE and the oxygenated Fenton’s reagent (Fe2+/DTPA/H2O2) in the presence of aliphatic alcohols or formate as a superoxide generating system revealed 2-OH-E+ as a major product. Formation of 2-OH-E+ by the Fenton’s reagent without additives was shown to be superoxide dismutase-sensitive and we attribute the formation of superoxide radical anion to the one-electron reduction of oxygen by the DTPA-derived radical. Addition of tert-butanol, DMSO, and potassium bromide to the Fenton’s system caused inhibition of 2-OH-E+ formation. Results indicate that reducing and oxidizing radicals have differential effects on the formation of 2-OH-E+. [Copyright &y& Elsevier]

Radical cations of 1,4-dialkoxybenzenes 1 and 2 and alkyl 1,4-dialkoxybenzenes 3–9 generated in oxidation of the parent donors by perfluorodi[1-(2-fluorosulfonyl)ethoxy]propionyl peroxide 10 at -40°C and pentafluorobenzoyl peroxide 11 at 15°C were observed by ESR. Radical cation 6+, generated in other oxidation systems, i.e., Ce(SO4)2/THF, NH4/OAc and (NH4)2S2O8/HOAc, has also been investigated. Based on ESR observation and products analysis, an electron-transfer mechanism of the oxidation reaction is proposed and the influencing factors on hyperfine splitting constants of the radical cations are discussed. [ABSTRACT FROM AUTHOR]

Abstract: The oxidation of p-methylanisole 3a, dialkoxybenzenes 3b, 3c and alkyl dialkoxybenzenes 3d–h by perfluorodi[1-(2-fluorosulfonyl) ethoxy]propionyl peroxide 1 afforded main products 4-ω-fluorosulfonylperfluoroalkyl-4-alkoxy-2,5-cyclohexa-dienones and minor ring ω-fluorosulfonylperfluoroalkylation products. The electron transfer mechanism of the reactions is also proved by ESR detection of the radical cations of the donor molecules. [Copyright &y& Elsevier]

Abstract: The stereoselective intramolecular cyclization of epoxypropyl cinnamyl amines mediated by substoichiometric quantities of CAN leading to the synthesis of functionalized piperidines and the formation of a supramolecular assembly of the latter with ethyl acetate is described. [Copyright &y& Elsevier]

Abstract: Pulse radiolysis technique has been employed to study the reaction of different oxidizing and reducing radicals with mangiferin. The reaction of OH radical showed the formation of transient species absorbing in 380–390 and 470–480nm region. The reaction with specific one-electron oxidants (N3 , CCl3O2 ) also showed the formation of similar transient absorption bands and is assigned to phenoxyl radicals. The pK a values of the transient species have been determined to be 6.3 and 11.9. One-electron oxidation potential of mangiferin at pH 9 has been found to be 0.62V vs. NHE. The reaction of eaq − showed the formation of transient species with λ max at 340nm, which is assigned to the ketyl anion radical formed on addition of eaq − at carbonyl site. Reactions of one-electron oxidised mangiferin radicals with ascorbic acid have also been studied. [Copyright &y& Elsevier]