Structures,g-tensors,and hyperfine coupling constants of L-α-alanine radicals in radiation dosimetry: An ab initio molecular dynamics simulation study

Alanine is used as a transfer standard dosimeter for gamma ray and electron beam calibration. An important factor affecting its dosimetric response is humidity which can lead to errors in absorbed dose calculations. Ab initio molecular dynamics calculations were performed to determine the environmental effects on the electron paramagnetic resonance (EPR) parameters of L-α-alanine radicals in acidic and alkaline solutions. A new result, not dissimilar to the closed-shell amino acid molecule alanine, is that the non-zwitterionic form of the alanine radical is the stable form in the gas phase while the zwitterionic neutral alanine radical is not a stable structure in the gas phase. Geometric and EPR parameters of radicals in both gas and solution phases are found to be dependent on hydrogen bonding of water molecules with the polar groups and on dynamic solvation. Calculations on the optimized free radicals in the gas phase revealed that for the neutral radical, hydrogen bonding to water molecules drives a decrease in the magnitudes of g-tensor components g _xx and g _yy without affecting neither g _zz component nor the hyperfine coupling constants (HFCCs). The transfer from the gas to solution phase of the alanine radical anion is accompanied with an increase in the spin density on the carboxylic group's oxygen atoms. However, for the neutral radical, this transfer from gas to solution phase is accompanied with the decrease in the spin density on oxygen atoms. Calculated isotropic HFCCs and g-tensor of all radicals are in good agreement with experiment in both acidic and alkaline solutions.     

Voltammetric Study of Nitro Radical Anion Generated from Some Nitrofuran Compounds of Pharmacological Significance

The electrochemical behavior of 2‐(5‐amino‐ 1,3,4‐oxadiazolyl)‐5‐nitrofuran (NF359) and its comparison with well‐known drugs such as nifurtimox (NFX) and nitrofurazone (NFZ) in protic, mixed and aprotic media by cyclic voltammetry, tast and differential pulse polarography was studied. All the compounds were electrochemically reducible in all media being the reduction of the nitrofuran group the main voltammetric signal. The one‐electron reduction couple due to the nitro radical anion formation was visualized in mixed (for NF359 and NFZ) and aprotic media (for all compounds). By applying a cyclic voltammetric methodology we have calculated the decay constants (k₂) of the corresponding nitro radical anions in mixed and aprotic media. In mixed medium data fit well with a disproportionation reaction of the nitro radical anion but in aprotic medium fit better with a dimerization reaction. Also, considering cyclic voltammetric measurements in aprotic media we have estimated the reduction potential of the RNO₂/RNO₂^.? couple in aqueous medium, pH 7 (E¹₇ values) finding very good correlation with E¹₇ values obtained by pulse radiolysis. Furthermore we have calculated the equilibrium constants from the electron transfer from nitro radical anion to oxygen (k_O2) finding that nitro radical anion from NF359 is thermodynamically favored to react with oxygen in respect to both NFZ and NFX.     

EPR and Spectrophotometric Studies of Free Radicals (O2°−, °OH, BPD-MA°−) and Singlet Oxygen (1O2) Generated by Irradiation of Benzoporphyrin Derivative Monoacid Ring A

Abstract— Benzoporphyrin derivative monoacid ring A (BPD-MA), a chlorin-type molecule, is a new photosensitizer currently in phase II clinical trials for the treatment by pho-todynamic therapy of cancerous lesions, psoriasis and pathologic neovascularization. The photochemistry (type I and/or II) of BPD-MA has been studied in homogeneous solution and in aqueous dispersions of unilamellar liposomes of dipalmitoylphosphatidylcholine (DPPC) using electron paramagnetic resonance and spectrophotometric methods. When oxygen-saturated solutions of BPD-MA were illuminated with 690 nm light, singlet oxygen (¹O₂), superoxide anion radical (O₂^?), hydroxyl radical (OH) and hydrogen peroxide (H₂O₂) were formed. The BPD-MA generates ¹O₂ with a quantum yield of ca 0.81 in ethanolic solution. The quantum yield does not change upon incorporation of BPD-MA into liposomes of DPPC. The superoxide anion radical was generated by the BPD-MA anion radical (BPD-MA^?) via electron transfer to oxygen, and this process was significantly enhanced by the presence of electron donors. The rate of production of 0₂ was also dependent on the concentration of BPD-MA used (3-100 μM). The quantum yield of O₂^?was found to be 0.011 and 0.025 in aqueous solution and DPPC liposomes, respectively. Moreover, O₂^_upon dis-proportionation can generate H₂O₂ and ultimately the highly reactive OH via the Fenton reaction. In anaerobic homogeneous solution, BPD-MA^?was predominantly photoproduced via the self-electron transfer between the excited- and ground-state species. The presence of an electron donor significantly promotes the reduced form of BPD-MA. These findings suggest that the photodynamic action of BPD-MA may proceed via both type I and type II mechanisms.     

Theoretical studies of electron and hydrogen transfer reactions between semiquinone radicals and oxygen

 To explore the interactions between ubiquinones and oxygen in living organisms, the thermodynamics of a series of electron and hydrogen transfer reactions between semiquinone radicals, as well as their corresponding protonated forms, and oxygen, singlet or triplet, were studied using the hybrid Hartree–Fock–density functional theory method Becke's three parameter hybrid method with the Lee, Yang, and Parr correlation functional. Effects of the solvent and of the isoprenyl tail on the electron and hydrogen transfer reactions were also investigated. It is found that semiquinone radicals (semiquinone anion radicals or protonated semiquinone radicals) cannot react with triplet oxygen to form the superoxide anion radical O₂ ⁻. In contrast, neutral quinones can scavenge O₂ ⁻ efficiently. In the gas phase, only protonated semiquinone radicals can react spontaneously with singlet oxygen to produce peroxyl radical (HO₂). However, both semiquinone anion radicals and protonated semiquinone radicals can react with singlet oxygen to produce harmful oxygen radicals (O₂ ^{− a l l b u l l} and HO₂, respectively) in aqueous and protein environments. The free-energy changes of the corresponding reactions obtained for different ubiquinone systems are very similar. It clearly shows that the isoprenyl tail does not influence the electron and hydrogen transfer reactions between semiquinone radicals and oxygen significantly. Results of electron affinities, vertical ionization potentials, and proton affinities also show that the isoprenyl tail has no substantial effect on the electronic properties of ubiquinones. Received: 3 July 2000 / Accepted: 6 September 2000 / Published online: 21 December 2000     

Screening Nitrogen‐Rich Bases and Oxygen‐Rich Acids by Theoretical Calculations for Forming Highly Stable Salts

Nitrogen‐rich heterocyclic bases and oxygen‐rich acids react to produce energetic salts with potential application in the field of composite explosives and propellants. In this study, 12 salts formed by the reaction of the bases 4‐amino‐1,2,4‐trizole (A), 1‐amino‐1,2,4‐trizole (B), and 5‐aminotetrazole (C), upon reaction with the acids HNO₃ (I), HN(NO₂)₂ (II), HClO₄ (III), and HC(NO₂)₃ (IV), are studied using DFT calculations at the B97‐D/6‐311++G** level of theory. For the reactions with the same base, those of HClO₄ are the most exothermic and spontaneous, and the most negative Δ_rG_m in the formation reaction also corresponds to the highest decomposition temperature of the resulting salt. The ability of anions and cations to form hydrogen bonds decreases in the order NO₃^?>N(NO₂)₂^?>ClO₄^?>C(NO₂)₃^?, and C⁺>B⁺>A⁺. In particular, those different cation abilities are mainly due to their different conformations and charge distributions. For the salts with the same anion, the larger total hydrogen‐bond energy (E_H,tot) leads to a higher melting point. The order of cations and anions on charge transfer (q), second‐order perturbation energy (E₂), and binding energy (E_b) are the same to that of E_H,tot, so larger q leads to larger E₂, E_b, and E_H,tot. All salts have similar frontier orbitals distributions, and their HOMO and LUMO are derived from the anion and the cation, respectively. The molecular orbital shapes are kept as the ions form a salt. To produce energetic salts, 5‐aminotetrazole and HClO₄ are the preferred base and acid, respectively.     

Ionic Assembly,Anion–π, Magnetic,and Electronic Attributes of Ambient Stable Naphthalenediimide Radical Ions

Organic spin-based molecular materials are considered to be attractive for the generation of functional materials with emergent optoelectronic, magnetic, or magneto-conductive properties. However, the major limitations to the utilization of organic spin-based systems are their high reactivity, instability, and propensity for dimerization. Herein, we report the synthesis, characterization, and magnetic and electronic studies of three ambient stable radical ions ( 1 a^.+ , 1 b^.+ , and 1 c^.+ ). The radical ions 1 b^.+ and 1 c^.+ with BPh₄⁻ and BF₄⁻ counter anions, respectively, were synthesized in excellent yields by means of anion metathesis of 1 a^.+ with Br⁻ as its counter anion. Notably, synthesis of 1 a^.+ was achieved in an ecofriendly, solvent-free protocol. The radical ions were characterized by means of single-crystal X-ray diffraction studies, which revealed the discrete nature of the radical ions and extensive hydrogen-bonding interactions within the radical ions and with the counter anions. Thus, radical ions can be organized to form infinite supramolecular arrays using weak noncovalent interactions. In addition, the Br⁻, BF₄⁻, and BPh₄⁻ anions formed diverse types of anion–π interactions with the naphthalene and imide rings of the radical ions. The radical ions were characterized by means of X-band electron paramagnetic resonance (EPR) spectroscopy in solution and in the solid state. Magnetic studies revealed their paramagnetic nature in the range of 10 to 300 K. The radical ions exhibited high resistivity approaching the gigaohm (GΩ) scale. In addition, the radical ions exhibited panchromism.     

不同加成数C60精氨酸衍生物的合成及其清除活性氧自由基的性能

通过控制反应配比, 首次合成了三种具有不同加成数目的水溶性C₆₀精氨酸衍生物, C₆₀[HNC(NH)NH(CH₂)₃CH(NH₂)COOH]_nH_n (n＝2, 6, 8). 采用FT-IR, UV, RF, ¹H NMR, ¹³C NMR, LC-MS, EA, 粒径分析, 透射电镜等手段对其结构进行了表征. 同时采用化学发光法考察了三种具有不同加成数目的C₆₀精氨酸衍生物对活性氧自由基(超氧阴离子O₂^－.及羟自由基•OH)清除能力, 结果表明, C₆₀精氨酸衍生物对活性氧自由基具有优良的清除能力, 且清除能力与加成基团供电效应、空间位阻及C₆₀精氨酸衍生物在水中的聚集形态等因素密切相关.     

Recognition of amino acids and anions by a Zn(Ⅱ)-methylazacalix[4]pyridine complex

As a powerful macrocyclic host molecule with unique conformation and cavity structure that are fine-tuned by the bridging nitrogen atoms, methylazacalix[4]pyridine (MACP-4) has been shown to selectively recognize Zn2+ and form stable Zn(Ⅱ)-MACP-4 complexes both in solid state and solution with an association constant up to 5.97 (logKs). The molecular recognition of Zn(Ⅱ)-MACP-4 complexes towards various amino acids and anions with different geometry was investigated by using the spectral titration methods a...     

Reactivity of Singlet Oxygen Toward Proteins: The Effect of Structure in Basic Pancreatic Trypsin Inhibitor and in Ribonuclease A

The reactions of singlet oxygen, ¹O₂, with large peptides have been described previously. It was found that even in these systems, which in their native form are generally not supposed to possess a stable structure in solution, the polypeptide does impede the access of ¹O₂ to the amino acids that react readily with ¹O₂. Here we describe the ¹0₂ reaction with two proteins of well-defined structure. The quenching of ¹O₂ by bovine pancreatic trypsin inhibitor (BPTI) and by ribonuclease A (RNase A) was compared to that of a solution at the same concentration as those of its constituent amino acids that react readily with ¹O₂. The proteins were studied in their native form, when partly denatured by splitting their S-S bonds and when fully denatured. It was found that while in the native form the quenching rate constant was seven times lower in BPTI (2.2 vs 15.2 times 10⁷WM^-1 s^-1) and three times lower in RNase A (11.0 vs 32 times 10⁷M^-l s^-1) than in a mixture of its constituent amino acid residues, it increased upon denaturation reaching in the fully denatured state the value of the corresponding amino acid mixture. More striking is the effect of the protein structure when comparing the fraction of the encounters between ¹O₂ and protein, which cause damage to the protein, as reflected in the decrease of its biological activity. This decrease is assumed to be due to the chemical (oxidative) reactions of ¹O₂ in the protein. In the exceptionally stable BPTI the fraction of such encounters was 0.05 and in RNase A it was 0.2, whereas for the amino acid tryptophan in solution, 0.7 of the collisions with ¹O₂ led to a chemical reaction.     

Enzymatic oxidation of lignin and compounds modeling it. III. Formation of singlet oxygen in the peroxidase oxidation of lignin

The main emitters of radiation in the aerobic oxidation of lignin are the carbonyl groups in an excited state and singlet oxygen. It has been shown that the main source of O₂(¹Δ) may be the radical anion O^?·₂. Singlet oxygen and the radical anion are by-products of the radical oxidation of lignin.     

Unearthing the Mechanism of Prebiotic Nitrile Bond Reduction in Hydrogen Cyanide through a Curious Association of Two Molecular Radical Anions

HCN is clearly associated with the prebiotic chemical evolution of life. It has been known for decades that the radiolysis of HCN solutions produces sugars, amino acids and nucleobases. Remarkably, recent experimental studies have shown that the photolytic reduction of aqueous HCN by a photoredox reagent [Cu(CN)₃]^2? specifically yields sugars, which are the essential building blocks of RNA. Although a mechanistic understanding of such reductions with solvated electrons is poor, the general consensus is that they involve neutral free radicals. We show herein through the use of electronic structure studies and molecular simulations that the reduction of the nitrile bond of HCN is initiated through the formation of a molecular dipole‐bound anion from the photoredox reagent. Our theoretical studies show how HCN binds to the photoexcited reagent and then extracts an electron from the reagent and is ultimately detached as a dipole‐bound anion. The dipole‐bound anionic form of [HCN]^? can easily convert into a solvated valence‐bound form of [HCN]^?. After the formation of solvated [HCN]^?, an extraordinary chemical event ensues through a counter‐intuitive coupling of two valence‐bound anions to form a solvated molecular dianionic intermediate, [HCN]₂^2?. Finally, a proton‐coupled electron transfer occurs within the dianionic entity to complete the reduction. This mechanistic scenario is applicable to the reduction of other prebiotic nitrile species and avoids neutral radical‐based pathways, thereby preventing the proliferation of reactive species and preserving chemical selectivity. Furthermore, we show how such similar nitrile reduction pathways operate to yield the sugar precursors.     

Photosensitized Oxidation of Tetrabromobisphenol A by Humic Acid in Aqueous Solution†

The brominated flame retardant 3,3′,5,5′‐tetrabromobisphenol A (TBBPA) may accumulate in the environment, including surface waters, and degrade there to potentially toxic products. We have previously shown that singlet oxygen (¹O₂), produced by irradiation of rose bengal with visible light, oxidizes Triton X‐100‐solubilized TBBPA to yield the 2,6‐dibromo‐p‐benzosemiquinone anion radical while consuming oxygen (Environ. Sci. Technol. 42 , 166, 2008). Here, we report that a similar ¹ O ₂ ‐induced oxidation can be initiated in aqueous solutions by the irradiation of TBBPA dissolved in a humic acid (HA) solution. HA is a known weak ¹ O ₂ photosensitizer and we indeed detected the infrared ¹ O ₂ phosphorescence from HA preparations in D ₂ O. When an aqueous preparation of HA was irradiated (λ > 400 nm) in the presence of TBBPA, oxygen was consumed, and the 2,6‐dibromo‐ p ‐benzosemiquinone anion radical was generated and detected using electron paramagnetic resonance. Radical formation and oxygen consumption were inhibited by sodium azide, a singlet oxygen quencher. Our results suggest that solar radiation, in the presence of HA, may play an important role in the photodegradation of TBBPA in the aquatic environment.     

Boron as a Powerful Reductant: Synthesis of a Stable Boron‐Centered Radical‐Anion Radical‐Cation Pair

Despite the fundamental importance of radical‐anion radical‐cation pairs in single‐electron transfer (SET) reactions, such species are still very rare and transient in nature. Since diborenes have highly electron‐rich B? B double bonds, which makes them strong neutral reductants, we envisaged a possible realization of a boron‐centered radical‐anion radical‐cation pair by SET from a diborene to a borole species, which are known to form stable radical anions upon one‐electron reduction. However, since the reduction potentials of all know diborenes (E_1/2=?1.05/?1.55 V) were not sufficiently negative to reduce MesBC₄Ph₄ (E_1/2=?1.69 V), a suitable diborene, IiPr?(iPr)B?B(iPr)?IiPr, was tailor‐made to comply with these requirements. With a halfwave potential of E_1/2=?1.95 V, this diborene ranks amongst the most powerful neutral organic reductants known and readily reacted with MesBC₄Ph₄ by SET to afford a stable boron‐centered radical‐anion radical‐cation pair.     

Detection of Cyclo‐N5− in THF Solution

Compelling evidence has been found for the formation and direct detection of the cyclopentazole anion (cyclo‐N₅^?) in solution. The anion was prepared from phenylpentazole in two steps: reduction by an alkali metal to form the phenylpentazole radical anion, followed by thermal dissociation to yield cyclo‐N₅^?. The reaction solution was analyzed by HPLC coupled with negative mode mass spectrometry. A signal with m/z 70 was eluted about 2.1 min after injection of the sample. Its identification as N₅ was supported by single and double labeling with ¹⁵N, which yielded signals at m/z=71 and 72, respectively, with identical retention times in the HPLC column. MS/MS analysis of the m/z=70 signal revealed a dissociation product with m/z=42, which can be assigned to N₃^?. To our knowledge this is the first preparation of cyclo‐N₅^? in the bulk. The compound is indefinitely stable at temperatures below ?40 °C, and has a half‐life of a few minutes at room temperature.     

Electrochemical reduction of 4-aminopyrimidine and cytosine in dimethyl sulfoxide

The electrochemical reduction in dimethyl sulfoxide of cytosine (4-amino-2-hydroxypyrimidine) and one of its model compounds (4-aminopyrimidine) has been examined. Initially, each pyrimidine (RH) undergoes a reversible, diffusion-controlled one-electron reduction of the 3,4 N=C double bond to the radical anion (RH⁻, which can dimerize or can react with the parent compound (father-son reaction) to form the neutral free radical (RH₂) and the pyrimidine anion (R⁻); the radical can dimerize or be further reduced, perhaps after effectve protonation; the anion forms a redox couple with Hg(1)−Hg(0). Other coupled reactions, which may occur under suitable conditions, include reaction between anionic dimer (⁻RH−RH⁻) and RH, proton-assisted decomposition of dimer to form reducible RH₃⁺, and deamination of the two-electron reduction product (RH₃), which is a gem diamine, to generate 2-hydroxypyrimidine or pyrimidine itself. The effects on the electrochemical redox pattern of added water, strong acid (HClO₄), weak acid (chloroacetic and benzoic acids), and strong base (Et₄NOH) are described.     

ESR.-Spektren des Radikal-Anions des syn-1, 6; 8, 13-Bis-oxido-[14]annulens

The ESR.-spectra of the radical anion of syn-1, 6; 8, 13-bis-oxido-[14]annulene have been recorded. The hyperfine structure of the electrolytically generated anion (solvent: N, N-dimethylformamide; gegenion: Et₄N^⊕) is that of an unassociated species; on the other hand, evidence of strong ion-pairing can be derived from the spectra of chemically prepared anions (solvent: 1,2-dimethoxyethane; gegenion: K⊕ or Na⊕). The distribution of the n-spin population confirms the conclusion previously drawn for the radical anion of 1,6-oxido-[70]annulene that the overall effect of the oxygen bridging is electron repelling.     

Neutralization–reionization efficiencies for gaseous [C3Hn]+ Ions

A neutralization-reionization study of [C₃H_n]⁺ ions, n = 6?0, shows that neutralization efficiencies are larger for hydrocarbon radical cations than they are for even-electron carbocations with one more H atom. Reionization efficiencies to positive ions do not depend appreciably on the electronic properties of the neutral species undergoing reionization. However, reionization efficiencies to negative ions increase dramatically with the degree of unsaturation, by nearly two orders of magnitude, from C₃H₆ to C₃. All C₃H_n neutrals studied survive intact neutralization to produce a considerable fraction of stable, non-dissociating [C₃H_n]⁺ upon cationization. All C₃H_n radicals (n = 5, 3, 1) can be transferred collisionally to stable even-electron anions. For the C₃H_n hydrocarbon molecules studied (n = 6, 4, 2, 0) the stability of the molecular radical anion increases substantially with the degree of unsaturation.     

Does deprotonated benzoic acid lose carbon monoxide in collision-induced dissociation?

Decarboxylation is known to be the major fragmentation pathway for the deprotonated carboxylic acids in collision-induced dissociation (CID). However, in the CID mass spectrum of deprotonated benzoic acid (m/z 121) recorded on a Q-orbitrap mass spectrometer, the dominant peak was found to be m/z 93 instead of the anticipated m/z 77. Based on theoretical calculations, ¹⁸O-isotope labeling and MS³ experiments, we demonstrated that the fragmentation of benzoate anion begins with decarboxylation, but the initial phenide anion (m/z 77) can react with trace O₂ in the mass analyzer to produce phenolate anion (m/z 93) and other oxygen-containing ions. Thus oxygen adducts should be considered when annotating the MS/MS spectra of benzoic acids.     

Novel species in the electrochemical reduction of a metalmetal bond bridged by a bidentate fluorophosphine

The purple bridged bimetallic complex [CH₃N(PF₂)₂]₃Co₂(CO)₂ undergoes successive chemically and electrochemically reversible one-electron reductions to the corresponding green radical anion and pale-yellow dianion. The radical anion is relatively unreactive towards oxygen and methyl iodide. The dianion is not only reactive towards oxygen and methyl iodide but also captures small positively charged species (e.g. Li⁺ and H⁺) with significant alteration of its chemical properties.     

Reactivity of Tyr–Leu and Leu–Tyr dipeptides: identification of oxidation products by liquid chromatography–tandem mass spectrometry

The exposure of peptides and proteins to reactive hydroxyl radicals results in covalent modifications of amino acid side‐chains and protein backbone. In this study we have investigated the oxidation the isomeric peptides tyrosine–leucine (YL) and leucine–tyrosine (LY), by the hydroxyl radical formed under Fenton reaction (Fe²⁺/H₂O₂). Through mass spectrometry (MS), high‐performance liquid chromatography (HPLC‐MS) and electrospray tandem mass spectrometry (HPLC‐MSⁿ) measurements, we have identified and characterized the oxidation products of these two dipeptides. This approach allowed observing and identifying a wide variety of oxidation products, including isomeric forms of the oxidized dipeptides. We detected oxidation products with 1, 2, 3 and 4 oxygen atoms for both peptides; however, oxidation products with 5 oxygen atoms were only present in LY. LY dipeptide oxidation leads to more isomers with 1 and 2 oxygen atoms than YL (3 vs 5 and 4 vs 5, respectively). Formation of the peroxy group occurred preferentially in the C‐terminal residue. We have also detected oxidation products with double bonds or keto groups, dimers (YL–YL and LY–LY) and other products as a result of cross‐linking. Both amino acids in the dipeptides were oxidized although the peptides showed different oxidation products. Also, amino acid residues have shown different oxidation products depending on the relative position on the dipeptide. Results suggest that amino acids in the C‐terminal position are more prone to oxidation. Copyright © 2009 John Wiley & Sons, Ltd.