Microhydration of the guanine-cytosine (GC) base pair in the neutral and anionic radical states: a density functional study

A density functional study of the effects of microhydration on the guanine-cytosine (GC) base pair and its anion radical is presented. Geometries of the GC base pair in the presence of 6 and 11 water molecules were fully optimized in the neutral (GC-nH2O) and anion radical [(GC-nH2O)*-] (n = 6 and 11) states using the B3LYP method and the 6-31+G** basis set. Further, vibrational frequency analysis at the same level of theory (B3LYP/6-31+G**) was also performed to ensure the existence of local minima in these hydrated structures. It was found that water molecules surrounding the GC base pair have significant effects on the geometry of the GC base pair and promote nonplanarity in the GC base pair. The calculated structures were found to be in good agreement with those observed experimentally and obtained in molecular dynamics (MD) simulation studies. The water molecules in neutral GC-nH2O complexes lie near the ring plane of the GC base pair where they undergo hydrogen bonding with both GC and each other. However, in the GC anion radical complexes (GC-nH2O, n = 6, 11), the water molecules are displaced substantially from the GC ring plane. For GC-11H2O*-, a water molecule is hydrogen-bonded with the C6 atom of the cytosine base. We found that the hydration shell initially destabilizes the GC base pair toward electron capture as a transient anion. Energetically unstable diffuse states in the hydration shell are suggested to provide an intermediate state for the excess electron before molecular reorganization of the water molecules and the base pair results in a stable anion formation. The singly occupied molecular orbital (SOMO) in the anion radical complexes clearly shows that an excess electron localizes into a pi orbital of cytosine. The zero-point-energy (ZPE-) corrected adiabatic electron affinities (AEAs) of the GC-6H2O and GC-11H2O complexes, at the B3LYP/6-31+G** level of theory, were found to be 0.74 and 0.95 eV, respectively. However, the incorporation of bulk water as a solvent using the polarized continuum model (PCM) increases the EAs of these complexes to 1.77 eV.     

Activation barriers in the homolytic cleavage of radicals and ion radicals

As revealed by several experimental examples, radicals and ion radicals may, in contrast with closed-shell molecules, undergo exothermic homolytic cleavages (.A..B --> A: +.B) with substantial activation barriers. A two-state semiclassical model is proposed for explaining the existence of the barrier and estimating its magnitude. It is based on the intersection of the potential energy surfaces characterizing the dissociation of a bonding state, .A..B -->.A. +.B, on one hand, and the approach to bonding distance of a repulsive state, A: +.B --> A therefore B, on the other. After inclusion of the bond cleavage and formation as Morse curves in the normal-mode analysis, a simple activation driving force relationship is obtained, the two main ingredients of the intrinsic barrier being the triplet excitation energy of the A moiety and the pi*--> sigma* excitation energy in .A-B. The model is then tested by quantum chemical calculations, first on a simplified system to evaluate the calculation techniques and then on a real system. A comparison of the model predictions with experiment is finally performed using the rate data recently gathered for the cleavage of 4-cyanophenyl alkyl ether anion radicals, which cover a respectable range of driving forces, showing satisfactory agreement between theoretical predictions and experimental data.     

The 2'-deoxyadenosine-5'-phosphate anion, the analogous radical, and the different hydrogen-abstracted radical anions: molecular structures and effects on DNA damage

The 2'-deoxyadenosine-5'-phosphate (5'-dAMP) anion and its related radicals have been studied by reliably calibrated theoretical approaches. This study reveals important physical characteristics of 5'-dAMP radical related processes. One-electron oxidation of the 5'-dAMP anion is found on both the phosphoryl group and the adenine base with electron detachment energies close to that of phosphate. Partial removal of electron density from the adenine fragment leads to an extended pi system which includes the amine group of the adenine. Although the radical-centered carbon increases the extent of bonding with its adjacent atoms, it usually weakens the chemical bonds between the atoms at the alpha- and beta-positions. This tendency should be important in predicting the reactivity of the sugar-based radicals. The overall stability sequence of the H-abstracted 5'-dAMP anionic radicals is consistent with the analogous results for the H-abstracted neutral radicals of the adenosine nucleoside: aliphatic radicals > aromatic radicals. The negatively charged phosphoryl group attached to atom C(5)' of the ribose does not change this energetic sequence. All the H-abstraction produced 5'-dAMP radical anions are distonic radical anions. Studies have shown that the charge-radical-separating feature of the distonic radical anions is biologically relevant. This result should be important in understanding the reactive properties of these H-abstraction-produced anion radicals.     

Triplet state mechanism for electron transfer oxidation of DNA

The interaction of anthraquinone-2-sulfonate with nucleotides and DNA in acetonitrile and acetonitrile water solvent mixture have been studied using KrF laser photolysis aimed at elucidation of the reaction mechanism. Laser spectroscopy directly demonstrates that the initial species from interaction of anthraquinone-2-sulfonate with nucleotides are radical cations of nucleotides and radical anion of anthraquinone-2-sulfonate. In addition, formation of ion pair from interaction of any of nucleotides with anthraquinone-2-sulfonate is synchronous with decay of triplet anthraquinone-2-sulfonate, which has provided dynamic evidence for initiation of electron transfer from DNA bases to triplet anthraquinone-2-sulfonate. Moreover, direct observation of stabilized DNA guanyl radical cation from interaction of anthraquinone-2-sulfonate with DNA has provided initial evidence for selective cleavage of DNA at guanine moiety. The solvent-separated ion pairs in acetonitrile have evidently dissociated into free ions, thereby enabling independent study of the behavior of guanyl radical cations and radical anion of anthraquinone-2-sulfonate.     

Quantum chemical estimation of the possibility of the formation of chloro- and bromomethane radical anions and their fragmentation paths in the gas phase and in solution by MNDO and AM1 techniques

By semiempirical MNDO and AM1 methods it was shown that electron transfer on the chloro-and bromomethane molecules of the general formula CH_nHal_4–n (n=1–3) results either in a kinetically independent particle, i.e., a radical anion, or in C-Hal-bond cleavage with the formation of Hal^– and the respective radical. The enthalpy, activation energy of the reactions, and data on the geometry of the radical anion obtained show that the increasing the number of halogen atoms in the initial molecule and decreasing the solvent polarity favor radical anion stabilization. It was established that the cleavage of the C-H-bond in the radical anion is not favored energetically. Fragmentation at the C-H-bond can proceed according to the mechanism of dissociative electron capture by halomethane molecule only with additional factors favoring this reaction.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1886–1892, November, 1993.     

Tandem polar/radical crossover sequences for the formation of fused and bridged bicyclic nitrogen heterocycles involving radical ionic chain reactions,and alkene radical cation intermediates,performed under reducing conditions: scope and limitations

It is demonstrated that phosphorylated forms of beta-nitro alcohols provide an excellent means of entry into beta-(phosphatoxy)alkyl radicals on exposure to tributyltin hydride and AIBN in benzene at reflux. These radicals then undergo heterolytic cleavage of the phosphate group to yield alkene radical cation/phosphate anion contact ion pairs which are trapped intramolecularly in a tandem polar/radical crossover sequence involving radical ionic chain reactions by allylic and propargylic amines. The substitution pattern of the alkene radical cation dictates the cyclization mode, and this may be engineered to form fused ring systems by an initial exo-mode nucleophilic cyclization or bridged bicyclic systems when the nucleophilic attack takes place in the endo-mode.     

Deprotection by electrolysis: Part I. The application of homogeneous redox catalysis to the study of the reduction of tosyl esters and amides

The mechanism of the cathodic cleavage of tosylate protecting groups from alcohols, amines and phenols in dimethylformamide has been probed using the technique of homogeneous redox catalysis. Some nine tosyl esters and six tosyl amides have been investigated and it is confirmed that these deprotection reactions occur by cleavage of the anion radicals. The formal electrode potentials for the couples, neutral molecule/anion radical, are reported and it is shown that the rate constants for the cleavage of the anion radicals lie in the range 10⁴ s^?1 to >10⁸ s^?1. Indeed for aromatic amines and phenols, the homogeneous charge transfer between the catalyst and the substrate becomes the rate determining step.     

N,N'-dimethyl-N,N'-diarylurea anion radicals: an intramolecular reductive elimination

The one-electron reduction of tertiary N,N'-dimethyl-N,N'-diarylureas (aryl = phenyl, beta-naphthyl, alpha-naphthyl), in HMPA, results in anion radicals that undergo novel intramolecular reductive elimination reactions leading to the formation of the anion radicals of the corresponding biaryls. These results are due to face to face pi-pi stacking interactions involving the two aromatic rings in the urea systems. The overlapping p(pi)() orbitals on the ipso carbons of opposing aryl groups evolve into a sigma bond leading to the formation of the biaryl anion radical. In the case of the N,N'-dimethyl-N,N'-di-2-pyrenylurea system, there is a node in the LUMO of the number 2 carbon, and the parent anion radical remains intact.     

Zwitterion radicals and anion radicals from electron transfer and solvent condensation with the fingerprint developing agent ninhydrin.

Ninhydrin (the fingerprint developing agent) spontaneously dehydrates in liquid ammonia and in hexamethylphosphoramide (HMPA) to form indantrione, which has a sufficiently large solution electron affinity to extract an electron from the solvent (HMPA) to produce the indantrione anion radical. In liquid NH(3), the presence of trace amounts of amide ion causes the spontaneous formation of an anion radical condensation product, wherein the no. 2 carbon (originally a carbonyl carbon) becomes substituted with -NH(2) and -OH groups. In HMPA, the indantrione anion radical spontaneously forms condensation products with the HMPA to produce a variety of zwitterionic radicals, wherein the no. 2 carbon becomes directly attached to a nitrogen of the HMPA. The mechanisms for the formation of the zwitterionic paramagnetic condensation products are analogous to that observed in the reaction of ninhydrin with amino acids to yield Ruhemann's Purple, the contrast product in fingerprint development. The formation of anion and zwitterionic radical condensation products from ninhydrin and nitrogen-containing solvents may represent an example of a host of analogous polyketone-solvent reactions.     

苯甲醛在光催化反应中氧化还原选择性的理论研究

采用密度泛函理论方法在M06-2X/6-311G^*水平上模拟了不同反应条件下, TiO₂对苯甲醛的光催化还原和氧化的反应. 计算结果表明, 苯甲醛的光催化还原和氧化反应均可在常温下发生; 在缺氧但有乙醇存在的条件下, 乙醇分子可与氧化性物质发生反应, 生成醇自由基, 苯甲醛主要发生光催化还原反应生成苯甲醇; 在有氧气但无乙醇存在条件下, 还原性的光生电子被氧气捕获, 避免了苯甲醛被还原, 主要发生光催化氧化反应生成苯甲酸.     

Transient spectroscopy of ninhydrin

The photochemistry of ninhydrin in benzene and water was studied by laser flash photolysis and electron paramagnetic resonance. Its photochemistry was shown to be dependent on the solvent. In benzene, a triplet excited state was observed, which underwent hydrogen abstraction reactions or reduction to the radical anion. In water, the radical anion of ninhydrin was formed within the laser pulse (15 ns) at neutral pH, whereas the neutral ketyl radical was formed by protonation of the radical anion at low pH. A pKa of 0.77 was determined for the protonation equilibrium. The formation of hydrindantin is proposed to occur through the dimerization of the ketyl radical or the radical anion (or both). In addition, ninhydrin was shown to be a poor precursor for the photogeneration of hydroxyl radicals.     

Exciplex and radical ion intermediates in the photochemical reaction of 9-cyanophenanthrene with 2,3-dimethyl-2-butene

The photochemical reaction of 9-cyanophenanthrene and 2,3-dimethyl-2-butene, first reported by Mizuno, Pac and Sakurai, has been reinvestigated. The formation of a [2+2]-cycloadduct via a singlet exciplex is the exclusive reaction in the nonpolar solvents benzene and ethyl acetate. Photochemical behavior in polar solvents is far more complicated than previously reported. Mechanisms consistent with the effects of solvent polarity, methanol concentration, methanol deuteration, and light intensity upon product yields are proposed. Formation of a 9-cyanophenthrene anion radical and 2,3-dimethyl-2-butene cation radical is the primary photoinitiated process in polar solvent. The cation radical can undergo deprotonation to yield an allyl radical or nucleophilic attack by methanol to yield a methoxyalkyl radical. Covalent bonding of these radicals and the 9-cyanophenanthrene anion radical gives rise to the acyclic adducts obtained in polar solvents. The anion radical can also be protonated, leading ultimately to the formation of 9,10-dihydro-9-cyanophenanthrene.     

SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS—X. A SPIN-TRAPPING AND DIRECT ELECTRON SPIN RESONANCE STUDY OF THE PHOTOCHEMICAL PATHWAYS OF DAUNOMYCIN AND ADRIAMYCIN

Abstract— Irradiation of daunomycin (or adriamycin) and the spin trap 5,5-dimethyl-l-pyrroline-1-oxide (DMPO) at 490 nm in the presence or in the absence of air generated the hydroxyl radical adduct (DMPO-OH). The observed DMPO-OH signal was not affected by the addition of hydroxyl radical scavengers (ethanol, formate), suggesting that direct trapping of the hydroxyl radical was not involved. The DMPO-OH signal was insensitive to superoxide dismutase and catalase, which ruled out the possibility of superoxide or H₂O₂ involvement. These findings demonstrate that daunomycin (or adriamycin) does not generate hydroxyl radicals or superoxide radical anions when subjected to 490-nm excitation. However, when daunomycin (or adriamycin) was irradiated at 310 nm DMPO adducts derived from two carbon-centered radicals, superoxide and the hydroxyl radical were detected. The superoxide adduct of DMPO was abolished by the addition of SOD, providing unequivocal evidence for the generation of the superoxide anion radical. The daunomycin semiquinone radical, observed upon 310-nm irradiation of daunomycin in the absence of DMPO, appears to be the precursor of the superoxide radical anion. One of the carbon-centered radicals trapped by DMPO exhibited a unique set of hyperfine parameters and was identified as an acyl radical. This suggests that the known photochemical deacylation of daunomycin occurs via a homolytic cleavage mechanism. The free radicals generated photolytically from adriamycin and daunomycin may be involved in the etiology of the skin ulceration and inflammation caused by these drugs. A knowledge of the dependence of these photogenerated radicals on the wavelength of excitation may be important in the development of adriamycin and daunomycin for photodynamic therapy.     

Electron transfer in a radical ion pair: quantum calculations of the solvent reorganization energy

Results are presented for an investigation of intermolecular electron transfer (ET) in solution by means of quantum calculations. The two molecules that are involved in the ET reaction form a solvent-separated radical ion pair. The solvent plays an important role in the ET between the two molecules. In particular, it can give rise to specific solute-solvent interactions with the solutes. An example of specific interactions is the formation of a hydrogen bond between a protic solvent and one of the molecules involved in the ET. We address the study of this system by means of quantum calculations on the solutes immersed in a continuum solvent. However, when the solvent can give rise to hydrogen bond formation with the negatively charged ion after ET, we explicitly consider solvent molecules in the solute cavity, determining the hydrogen bond energetic contribution to the overall interaction energy. Solute-solvent pair distribution functions, showing the different arrangement of solvent molecules before and after ET in the first solvation shell, are reported. We provide results of the solvent reorganization energy from quantum calculations for both the two isolated fragments and the ion pair in solution. Results are in agreement with available experimental data.     

SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS—VI. IDENTIFICATION OF THE FREE RADICALS GENERATED DURING THE PHOTOLYSIS OF MUSK AMBRETTE, MUSK XYLENE AND MUSK KETONE

Musk ambrette (4-tert-butyl-3-methoxy-2,5-dinitrotoluene), a common component of perfumes, soaps, and some food flavorings, can cause cutaneous photosensitization reactions including photoallergy. These may be mediated through free radicals formed during photolysis. When musk ambrette was photolyzed under nitrogen in basic methanol, two distinct nitro anion radicals were identified by electron spin resonance. One radical was centered on a nitro group in the plane of the aromatic ring, while the other was centered on a nitro group twisted out of the plane of the ring due to steric hindrance by bulky substituents on either side of the group: the two radicals appeared to interconvert and maintain an equilibrium concentration ratio. Two closely related compounds which are also used in perfumes, but have not been reported to cause photosensitizing reactions, also produced free radicals during photolysis. Musk xylene (2,4,6-trinitro-1,3-dimethyl-5-tert-butylbenzene) generated two nitro anion radicals, both of which were centered on twisted nitro groups, while musk ketone (3,5-dinitro-2,6-dimethyl-4-tert-butylacetophenone) produced only one nitro anion radical, which is also twisted. Athough these nitro anion radicals are probably the first step in the photolysis of these nitroarornatic molecules, it seems likely that in vivo they will undergo further reduction to produce more reactive species including the corresponding nitroso and hydroxylamine derivatives. In addition, autoxidation of the nitro anion radical intermediate forms superoxide.     

Electronic structures of the free radicals derived from ascorbic acid and α-hydroxytetronic acid

Calculations on several free radicals derived from ascorbic acid, and α-hydroxytetronic acid are reported. The calculations have been carried out both with the INDO method and the ab initio UHF method. The calculated spin densities are only consistent with the assignment of the structure of the predominant radical derived from these molecules to the anion radical.     

Ion chemistry of 1H-1,2,3-triazole. 2. Photoelectron spectrum of the iminodiazomethyl anion and collision induced dissociation of the 1,2,3-triazolide ion

The 363.8 nm photoelectron spectrum of the iminodiazomethyl anion has been measured. The anion is synthesized through the reaction of the hydroxide ion (HO-) with 1 H-1,2,3-triazole in helium buffer gas in a flowing afterglow ion source. The observed spectrum exhibits well-resolved vibronic structure of the iminodiazomethyl radical. Electronic structure calculations have been performed at the B3LYP/6-311++G(d,p) level of theory to study the molecular structure of the ion. Equilibrium geometries of four possible conformers of the iminodiazomethyl anion have been obtained from the calculations. Spectral simulations have been performed on the basis of the calculated geometries and normal modes of these conformationally isomeric ions and the corresponding radicals. The spectral analysis suggests that the ions of two conformations are primarily formed in the aforementioned reaction. The relative abundance of the two conformers substantially deviates from the thermal equilibrium populations, and it reflects the potential energy surfaces relevant to conformational isomerization processes. The electron affinities of the ( ZE)- and ( EE)-iminodiazomethyl radicals have been determined to be 2.484 +/- 0.007 and 2.460 +/- 0.007 eV, respectively. The energetics of the iminodiazomethyl anion is compared with that of the most stable structural isomer, the 1,2,3-triazolide ion. Collision-induced dissociation of the 1,2,3-triazolide ion has also been studied in flowing afterglow-selected ion flow tube experiments. Facile fragmentation generating a product ion of m/ z 40 has been observed. DFT calculations suggest that fragmentation of the 1,2,3-triazolide ion to the cyanomethyl anion and N2 is exothermic. The stability of the ion is discussed in comparison with other azolide ions with different numbers of N atoms in the five-membered ring.     

Local ordering in liquids: solvent effects on the hyperfine couplings of the cyclohexadienyl radical

Ordering of solvent molecules in the vicinity of a dipolar free radical affects its hyperfine coupling constants (hfcs). Specifically, it is demonstrated how the variation of the experimental methylene proton and muon hfcs of the muoniated cyclohexadienyl radical in several solvents and solvent mixtures of varying polarity can be accounted for by a dipole-dipole reaction field model that is based on the model of Reddoch and Konishi (J. Chem. Phys. 1979, 70, 2121) which was developed to explain the solvent dependence of the 14N hfc in the di-tert-butyl-nitroxide radical. Ab initio calculations were carried out with the cyclohexadienyl radical in an electric field to model the electric field arising from the electric dipole moments of the surrounding solvent molecules. An extension of the model that includes the dipole-quadrupole interaction can account for the larger hfc in benzene compared with that in octadecane, and it is predicted that the hfc will be proportional to the concentration of quadrupole moments to the 4/3 power. The influence of hydrogen bonding between the radicals' pi electrons and the OH groups of the solvent on the hfcs is also discussed. Comparison with gas-phase data permits a separation of vibrational effects and reveals that approximately 28% of the temperature dependence in water is due to increasing solvent disorder.     

Collision induced dissociation of protonated N-nitrosodimethylamine by ion trap mass spectrometry: Ultimate carcinogens in gas phase

Collision induced dissociation of protonated N-nitrosodimethylamine (NDMA) and isotopically labeled N-nitrosodimethyl-d6-amine (NDMA-d6) was investigated by sequential ion trap mass spectrometry to establish mechanisms of gas phase reactions leading to intriguing products of this potent carcinogen. The fragmentation of (NDMA + H⁺) occurs via two dissociation pathways. In the alkylation pathway, homolytic cleavage of the N–O bond of N-dimethyl, N′-hydroxydiazenium ion generates N-dimethyldiazenium distonic ion which reacts further by a CH₃ radical loss to form methanediazonium ion. Both methanediazonium ion and its precursor are involved in ion/molecule reactions. Methanediazonium ion showed to be capable of methylating water and methanol molecules in the gas phase of the ion trap and N-dimethyldiazenium distonic ion showed to abstract a hydrogen atom from a solvent molecule. In the denitrosation pathway, a tautomerization of N-dimethyl, N′-hydroxydiazenium ion to N-nitrosodimethylammonium intermediate ion results in radical cleavage of the N–N bond of the intermediate ion to form N-dimethylaminium radical cation which reacts further through α-cleavage to generate N-methylmethylenimmonium ion. Although the reactions of NDMA in the gas phase are different to those for enzymatic conversion of NDMA in biological systems, each activation method generates the same products. We will show that collision induced dissociation of N-nitrosodiethylamine (NDEA) and N-nitrosodipropylamine (NDPA) is also a feasible approach to gain information on formation, stability, and reactivity of alkylating agents originating from NDEA and NDPA. Investigating such biologically relevant, but highly reactive intermediates in the condensed phase is hampered by the short life-times of these transient species.