Model studies of DNA C5' radicals. Selective generation and reactivity of 2'-deoxyadenosin-5'-yl radical

The reaction of hydrated electrons (e(aq)(-)) with 8-bromo-2'-deoxyadenosine has been investigated by radiolytic methods coupled with product studies and addressed computationally by means of DFT-B3LYP calculations. Pulse radiolysis revealed that this reaction was complete in approximately 0.3 mus, and, at this time, no significant absorption was detected. The spectrum of a transient developed in 20 mus has an absorbance in the range 300-500 nm (epsilon(max) congruent with 9600 M(-1) cm(-1) at 360 nm), and it was assigned to aromatic aminyl radical 3. Computed vertical transitions (TD-UB3LYP/6-311+G) are in good agreement with the experimental observations. Radical 3 is obtained by the following reaction sequence: one-electron reductive cleavage of the C-Br bond that gives the C8 radical, a fast radical translocation from the C8 to C5' position, and an intramolecular attack of the C5' radical at the C8,N7 double bond of the adenine moiety. The rate constant for the cyclization is 1.6 x 10(5) s(-1). On the basis of the theoretical findings, the cyclization step is highly stereospecific. The rate constants for the reactions of C5' and aminyl 3 radicals with different oxidants were determined by pulse radiolysis methods. The respective rate constants for the reaction of 2'-deoxyadenosin-5'-yl radical with dioxygen, Fe(CN)(6)(3)(-), and MV(2+) in water at ambient temperature are 1.9 x 10(9), 4.2 x 10(9), and 2.2 x 10(8) M(-1) s(-1). The value for the reaction of aminyl radical 3 with Fe(CN)(6)(3-) is 8.3 x 10(8) M(-1) s(-1), whereas the reaction with dioxygen is reversible. Tailored experiments allowed the reaction mechanism to be defined in some detail. A synthetically useful radical cascade process has also been developed that allows in a one-pot procedure the conversion of 8-bromo-2'-deoxyadenosine to 5',8-cyclo-2'-deoxyadenosine in a diastereoisomeric ratio (5'R):(5'S) = 6:1 and in high yield, by reaction with hydrated electrons in the presence of K(4)Fe(CN)(6).     

Chemical radiation studies of 8-bromo-2'-deoxyinosine and 8-bromoinosine in aqueous solutions

The reactions of hydrated electrons (e(aq) (-)) with 8-bromo-2'-deoxyinosine (8) and 8-bromoinosine (12) have been investigated by radiolytic methods coupled with product studies and have been addressed computationally by means of BB1K-HMDFT calculations. Pulse radiolysis revealed that one-electron reductive cleavage of the C--Br bond gives the C8 radical 9 or 13 followed by a fast radical translocation to the sugar moiety. Selective generation of a C5' radical occurs in the 2'-deoxyribo derivative, whereas in the ribo analogue the reaction is partitioned between the C5' and C2' positions with similar rates. Both C5' radicals undergo cyclizations, 10-->11 and 14-->15, with rate constants of 1.4 x 10(5) and of 1.3 x 10(4) s(-1), respectively. The redox properties of radicals 10 and 11 have also been investigated. A synthetically useful photoreaction has also been developed as a one-pot procedure that allows the conversion of 8 to 5',8-cyclo-2'-deoxyinosine in a high yield and a diastereoisomeric ratio (5'R)/(5'S) of 4:1. The present results are compared with data previously obtained for 8-bromoadenine and 8-bromoguanine nucleosides. Theory suggests that the behavior of 8-bromopurine derivatives with respect to solvated electrons can be attributed to differences in the energy gap between the pi*- and sigma*-radical anions.     

C5'-adenosinyl radical cyclization. A stereochemical investigation

A variety of substituted 2'-deoxyadenosin-5'-yl radicals 3 were generated under different reaction conditions. Radicals 3 underwent intramolecular cyclization onto the C8-N7 double bond of the adenine moiety leading to aminyl radicals (5'S,8R)-4 and (5'R,8R)-4 and, eventually, to the corresponding cyclonucleosides 5 and 6. The effect of the solvent, the nature of the substituents, and the generation method of radicals 3 on the stereoselectivity of the C5'-radical cyclization have been considered. The observed increase of the (5'S)/(5'R) ratio by increasing the bulkiness of the R1 group is explained in terms of steric repulsion between R1 and the purine moiety which favors the C5'-endo conformation, whereas the effect of the water solvent in promoting the (5'R)-stereoselective cyclization is ascribed to intermolecular hydrogen bonding stabilizing the C5'-exo conformation.     

The fate of C5' radicals of purine nucleosides under oxidative conditions

The factors that influence the reactivity of C5' radicals in purine moieties under aerobic conditions are unknown not only in DNA, but also in simple nucleosides. 5',8-Cyclopurine lesions are the result of a rapid C5' radical attack to the purine moieties before the reaction with oxygen. These well-known lesions among the DNA modifications were suppressed by the presence of molecular oxygen in solution. Here we elucidate the chemistry of three purine-substituted C5' radicals (i.e., 2'-deoxyadenosin-5'-yl, 2'-deoxyinosin-5'-yl, and 2'-deoxyguanosin-5'-yl) under oxidative conditions using gamma-radiolysis coupled with product studies. 2'-Deoxyadenosin-5'-yl and 2'-deoxyinosin-5'-yl radicals were selectively generated by the reaction of hydrated electrons (e(aq)(-)) with 8-bromo-2'-deoxyadenosine and 8-bromo-2'-deoxyinosine followed by a rapid radical translocation from the C8 to the C5' position. Trapping these two C5' radicals with Fe(CN)6(3-) gave corresponding hydrated 5'-aldehydes in good yields that were isolated and fully characterized. When an oxygen concentration in the range of 13-266 microM (typical oxygenated tissues) is used, the hydrated 5'-aldehyde is accompanied by the 5',8-cyclopurine nucleoside. The formation of 5',8-cyclopurines is relevant in all experiments, and the yields increased with decreasing O2 concentration. The reaction of HO(*) radicals with 2'-deoxyadenosine and 2'-deoxyguanosine under normoxic conditions was also investigated. The minor path of C5' radicals formation was found to be ca. 10% by quantifying the hydrated 5'-aldehyde in both experiments. Rate constants for the reactions of the 2'-deoxyadenosin-5'-yl with cysteine and glutathione in water were determined by pulse radiolysis to be (2.1 +/- 0.5) x 10(7) and (4.9 +/- 0.6) x 10(7) M(-1) s(-1) at 22 degrees C, respectively.     

Independent generation of C5'-nucleosidyl radicals in thymidine and 2'-deoxyguanosine

The synthesis of the C5' tert-butyl ketone of thymidine 1a and 2'-deoxyguanosine 2 is achieved by reaction of 5'-C-cyano derivatives with tert-butyl lithium followed by acid hydrolysis. The 5'R configuration is assigned by X-ray crystal structure determination of an opportunely protected derivative of 1a. The (5'S)-isomers of both nucleosides are not stable, and a complete decomposition occurs in the reaction medium. The photochemistry of 1a and 2 effectively produced the thymidin-5'-yl radical and the 2'-deoxyguanosin-5'-yl radical, respectively. In the thymidine system, the C5' radical is fully quenched in the presence of a physiological concentration of thiols. In the 2'-deoxyguanosine system, the C5' radical undergoes intramolecular attack onto the C8-N7 double bond of guanine leading ultimately to the 5',8-cyclo-2'-deoxyguanosine derivative. The cyclization of the 2'-deoxyguanosin-5'-yl radical occurs with a rate constant of ca. 1x10(6) s-1 and is highly stereoselective affording only the (5'S)-diastereomer.     

Laser flash photolysis evidence for styryl radical cation cyclization in the SET-induced photorearrangement of a p-methoxy-substituted 2-phenylallyl phosphite

The SET-induced photorearrangement of dimethyl 2-(4-methoxyphenyl)allyl phosphite, 9 (UV light, uranium glass filter, 9,10-dicyanoanthracene (DCA), biphenyl), gives phosphonate 12 in 83% isolated yield. Laser flash irradiation at 355 nm of oxygen saturated solutions of phosphite 9 containing DCA and biphenyl generates the transient UV spectrum of the biphenyl radical cation that is quenched by electron transfer from phosphite 9 (k(q) = 8.9 x 10(9) M(-1) s(-1) at 20 degrees C) to form the 4-methoxystyryl cation 10. The UV spectrum of 10 decays by a measured first-order rate constant of 8.0 x 10(6) s(-1), presumably to generate the cyclic distonic radical cation 11. Intermediate 10 was further characterized by measurement of the second-order rate constants for its reaction with azide, chloride, and bromide ions and with the neutral nucleophile trimethyl phosphite. This study provides the first spectroscopic evidence regarding the proposed mechanism (Schemes 1 and 2) for the SET-induced photorearrangements of dimethyl 2-arylallyl phosphites to the corresponding 2-arylallylphosphonates. Moreover, absolute rate constants for the intramolecular trapping of alkene radical cations have seldom been measured. The removal of the electron from the styryl moiety of phosphite 9, rather than from phosphorus, and the detectability of 10 arise from the stabilizing effect of the 4-methoxy substituent. These results, however, do not allow conclusions to be made concerning the site of removal of an electron in the SET-induced photorearrangement of dimethyl 2-phenylallyl phosphite 1 to phosphonate 6.     

Metallacarboranes as building blocks for polyanionic polyarmed aryl-ether materials

Polyanionic species have been obtained in high yield by a new route in the ring-opening reaction of cyclic oxonium [3,3'-Co(8-C4H8O2-1,2-C2B9H10)(1',2'-C2B9H11)] (2) by using carboxylic acids, Grignard reagents, and thiocarboranes as nucleophiles. The crystal structures of Na3(H2O)(C2H5OH)[1',3',5'-{3,3'-Co(8-O(CH2CH2O)2-1,2-C2B9H10)(1',2'-C2B9H11)}3-C6H3] and Na(H2O)[3,3'-Co(8-O(CH2CH2O)2C(O)CH3-1,2-C2B9H10)(1',2'-C2B9H11)] show that the chain contributes three or two oxygen atoms for coordination to Na(+), and interestingly, the [3,3'-Co(1,2-C2B9H11)2](-) moiety provides extra B-H coordination sites. These B-H...Na interactions in the solid state have also been confirmed by dynamic NMR studies in solution. These new polyanionic compounds that contain multiple carborane or metallacarborane clusters at their periphery may prove useful as new classes of boron neutron capture therapy compounds with enhanced water solubility and as a core to make a new class of dendrimers.     

The reactions of cytidine and 2'-deoxycytidine with SO4.- revisited. Pulse radiolysis and product studies

The reactions of SO4.- with 2'-deoxycytidine 1a and cytidine 1b lead to very different intermediates (base radicals with 1a, sugar radicals with 1b). The present study provides spectral and kinetic data for the various intermediates by pulse radiolysis as well as information on final product yields (free cytosine). Taking these and literature data into account allows us to substantiate but also modify in essential aspects the current mechanistic concept (H. Catterall, M. J. Davies and B. C. Gilbert, J. Chem. Soc., Perkin Trans. 2, 1992, 1379). SO4.- radicals have been generated radiolytically in the reaction of peroxodisulfate with the hydrated electron (and the H. atom). In the reaction of SO4.- with 1a (k = 1.6 x 10(9) dm3 mol-1 s-1), a transient (lambda max = 400 nm, shifted to 450 nm at pH 3) is observed. This absorption is due to two intermediates. The major component (lambda max approximately 385 nm) does not react with O2 and has been attributed to an N-centered radical 4a formed upon sulfate release and deprotonation at nitrogen. The minor component, rapidly wiped out by O2, must be due to C-centered OH-adduct radical(s) 6a and/or 7a suggested to be formed by a water-induced nucleophilic replacement. These radicals decay by second-order kinetics. Free cytosine is only formed in low yields (G = 0.14 x 10(-7) mol J-1 upon electron-beam irradiation). In contrast, 1b gives rise to an intermediate absorbing at lambda max = 530 nm (shifted to 600 nm in acid solution) which rapidly decays (k = 6 x 10(4) s-1). In the presence of O2, the decay is much faster (k approximately 1.3 x 10(9) dm3 mol-1 s-1) indicating that this species must be a C-centered radical. This has been attributed to the C(5)-yl radical 8 formed upon the reaction of the C(2')-OH group with the cytidine SO4(.-)-adduct radical 2b. This reaction competes very effectively with the corresponding reaction of water and the release of sulfate and a proton generating the N-centered radical. Upon the decay of 8, sugar radical 11 is formed with the release of cytosine. The latter is formed with a G value of 2.8 x 10(-7) mol J-1 (85% of primary SO4.-) at high dose rates (electron beam irradiation). At low dose rates (gamma-radiolysis) its yield is increased to 7 x 10(-7) mol J-1 due to a chain reaction involving peroxodisulfate and reducing free radicals. Phosphate buffer prevents the formation of the sugar radical at the SO4(.-)-adduct stage by enhancing the rate of sulfate release by deprotonation of 2b and also by speeding up the decay of the C(5)-yl radical into another (base) radical. Cytosine release in cytidine is mechanistically related to strand breakage in poly(C). Literature data on the effect of dioxygen on strand breakage yields in poly(C) induced by SO4.- (suppressed) and upon photoionisation (unaltered) lead us to conclude that in poly(C) and also in the present system free radical cations are not involved to a major extent. This conclusion modifies an essential aspect of the current mechanistic concept.     

The peculiar kinetics of the reaction between acetylene and the cyclopentadienyl radical

The cyclopentadienyl radical (cC(5)H(5)) is a fascinating molecule characterized by several peculiar properties, such as its high internal symmetry and resonance enhanced stability. This makes cC(5)H(5) one of the most abundant radicals present in high temperature gaseous environments, such as flames. Therefore it is generally considered an interesting candidate as the starting point of reaction pathways leading to the formation of polycyclic aromatic hydrocarbons (PAH) and soot in combustion processes. However, known reaction pathways are not able to explain some recent experimental findings concerning the rapid conversion of cC(5)H(5) into C(7)H(7) and C(9)H(8) in the presence of acetylene. In this work, we used ab initio calculations and quantum Rice-Ramsperger-Kassel (QRRK) theory to investigate the cC(5)H(5) + C(2)H(2) reaction kinetics. We found that cC(5)H(5) can add acetylene to form, through a fast and not previously known reaction, the heptatrienyl radical (cC(7)H(7)), which, in many ways, can be considered the superior homologue of cC(5)H(5). The calculated reaction kinetic constant is (2.2 x 10(11))exp(-6440/T(K)) cm(3) mol(-1) s(-1) and is in good agreement with experimental data, while that of the inverse process is (4.2 x 10(16))T(-1) exp(-30 850/T(K)) s(-1). In a successive reaction, cC(7)H(7) can add a second acetylene molecule to form indene, cC(9)H(8), and H. The forward and backward kinetic constants are (6.6 x 10(11))exp(-10 080/T(K)) and (4.2 x 10(14))exp(-27 300/T(K)) cm(3) mol(-1) s(-1), respectively. These two successive reactions, leading from a single C5 cycle to a bicyclic C5-C6 species, represent a new PAH growth mechanism, characterized by a C5-C7 ring enlargement reaction.     

Sequence selective recognition in the minor groove of dsDNA by pyrrole,imidazole-substituted bis-benzimidazole conjugates

A series of pyrrole, imidazole-substituted bis-benzimidazole conjugates, Py-Py-Im-gamma-biBenz, Py-Py-gamma-biBenz, Py-Im-gamma-biBenz, and Im-Py-gamma-biBenz (1-4), were prepared in an attempt to target dsDNA sequences possessing both A/T and G/C bps. The dsDNA interactions and sequence specificity of the conjugates have been characterized via spectrofluorometric titrations and thermal melting studies. All conjugates form 1:1 complexes with dsDNA at subnanomolar concentrations. The Im moiety selectively recognizes a G/C bp embedded in the A/T-rich binding site. This represents the first clear example of sequence selective recognition in a 1:1 motif.(1) The equilibrium association constant (K(1)) for complexation of a specific nine-bp dsDNA site, 5'-gcggTATGAAATTcgacg-3', by conjugate 1 is approximately 2.6 x 10(9) M(-1). Displacement of the G/C position or G/C-->A/T substitution within the nine-bp site decreases the K(1) by approximately 8-fold, whereas two continuous G/C bps decrease the K(1) by approximately 50-fold magnitude. The K(1) values for seven-bp dsDNA, 5'-gcggtaTGAAATTcgacg-3' and 5'-gcggtaCAAAATTcgacg-3', binding sites by conjugates Py-Im-gamma-biBenz (3) and Im-Py-gamma-biBenz (4) are approximately 2.3 x 10(9) and approximately 1.2 x 10(9) M(-1), respectively. However, the conjugates with no Im moiety, Py-Py-gamma-biBenz (2) and Py-Py-Py-gamma-biBenz (5 and 6), are specific for seven- to nine-bp A/T-rich sites and single A/T-->G/C bp substitution within the binding site decreases the K(1) values by 1-2 orders of magnitude.     

Reaction of O2 with the hydrogen atom in water up to 350 degrees C

The reaction of the H* atom with O2, giving the hydroperoxyl HO2* radical, has been investigated in pressurized water up to 350 degrees C using pulse radiolysis and deep-UV transient absorption spectroscopy. The reaction rate behavior is highly non-Arrhenius, with near diffusion-limited behavior at room temperature, increasing to a near constant limiting value of approximately 5 x 10(10) M(-1) s(-1) above 250 degrees C. The high-temperature rate constant is in near-perfect agreement with experimental extrapolations and ab initio calculations of the gas-phase high-pressure limiting rate. As part of the study, reaction of the OH* radical with H2 has been reevaluated at 350 degrees C, giving a rate constant of (6.0 +/- 0.5) x 10(8) M(-1) s(-1). The mechanism of the H* atom reaction with the HO2* radical is also investigated and discussed.     

Borane reaction chemistry. Alkyne insertion reactions into boron-containing clusters. Products from the thermolysis of [6,9-(2-HC[triple bond]C-C5H4N)2-arachno-B10H12

The stirring of [ortho-(HC[triple bond]C)-C(5)H(4)N] with [nido-B(10)H(14)] in benzene affords [6,9-{ortho-(HC[triple bond]C)-C(5)H(4)N}(2)-arachno-B(10)H(12)] 1 in 93% yield. In the solid state, 1 has an extended complex three-dimensional structure involving intramolecular dihydrogen bonding, which accounts for its low solubility. Thermolysis of 1 gives the known [1-(ortho-C(5)H(4)N)-1,2-closo-C(2)B(10)H(11)] 2 (13%), together with new [micro-5(N),6(C)-(NC(5)H(4)-ortho-CH(2))-nido-6-CB(9)H(10)] 3 (0.4%), [micro-7(C),8(N)-(NC(5)H(4)-ortho-CH(2))-nido-7-CB(10)H(11)] (0.4%) , 4 binuclear [endo-6'-(closo-1,2-C(2)B(10)H(10))-micro-(1(C),exo-6'(N))-(ortho-C(5)H(4)N)-micro-(exo-8'(C),exo-9'(N))-(ortho-(CH(2)CH(2))-C(5)H(4)N)-arachno-B(10)H(10)] (0.5%) 5, and [exo-6(C)-endo-6(N)-(ortho-(CH[double bond]CH)-C(5)H(4)N)-exo-9(N)-(ortho-(HC[triple bond]C)-C(5)H(4)N)-arachno-B(10)H(11)] 6. An improved solvent-free route to 2 is also presented. This set of compounds features an increasing cluster incorporation of the ethynyl moiety, initially by an effective internal hydroboration, affording an arachno to nido and then a nido to arachno:closo sequence of cluster geometry. An alternative low-temperature route to internal hydroboration is demonstrated in the room temperature reaction of [closo-B(11)H(11)][N(n)Bu(4)](2) with CF(3)COOH and [ortho-(HC[triple bond]C)-C(5)H(4)N], which gives [micro-1(C),2(B)-[ortho-C(5)H(4)N-CH(2)]-closo-1-CB(11)H(10)] 7 (40%) in which one carbon atom is incorporated into the cluster; a similar reaction with [ortho-(N[triple bond]C)-C(5)H(4)N] affords [N(n)Bu(4)][7-(ortho-N[triple bond]C-C(5)H(4)N)-nido-B(11)H(12)], 8 (68%) and stirring [ortho-(N[triple bond]C)-C(5)H(4)N] with [nido-B(10)H(14)] quantitatively affords the cyano analogue of 1, [6,9-{ortho-(N[triple bond]C)-C(5)H(4)N}(2)-arachno-B(10)H(12)] 9. All compounds were characterised by single-crystal X-ray diffraction analysis and NMR spectroscopy.     

A temperature-dependent relative-rate study of the OH initiated oxidation of n-butane: the kinetics of the reactions of the 1- and 2-butoxy radicals

The kinetics of the reactions of 1-and 2-butoxy radicals have been studied using a slow-flow photochemical reactor with GC-FID detection of reactants and products. Branching ratios between decomposition, CH3CH(O*)CH2CH3 --> CH3CHO + C2H5, reaction (7), and reaction with oxygen, CH3CH(O*)CH2CH3+ O2 --> CH3C(O)C2H5+ HO2, reaction (6), for the 2-butoxy radical and between isomerization, CH3CH2CH2CH2O* --> CH2CH2CH2CH2OH, reaction (9), and reaction with oxygen, CH3CH2CH2CH2O* + O2 --> C3H7CHO + HO2, reaction (8), for the 1-butoxy radical were measured as a function of oxygen concentration at atmospheric pressure over the temperature range 250-318 K. Evidence for the formation of a small fraction of chemically activated alkoxy radicals generated from the photolysis of alkyl nitrite precursors and from the exothermic reaction of 2-butyl peroxy radicals with NO was observed. The temperature dependence of the rate constant ratios for a thermalized system is given by k7/k6= 5.4 x 10(26) exp[(-47.4 +/- 2.8 kJ mol(-1))/RT] molecule cm(-3) and k9/k8= 1.98 x 10(23) exp[(-22.6 +/- 3.9 kJ mol(-1))/RT] molecule cm(-3). The results agree well with the available experimental literature data at ambient temperature but the temperature dependence of the rate constant ratios is weaker than in current recommendations.     

Nature of the chain propagation in the photostimulated reaction of 1-bromonaphthalene with sulfur-centered nucleophiles

The reactivity of -SC(NH)NH2 (1), MeCOS- (2), and PhCOS- (3) toward 1-naphthyl radicals was studied in DMSO. The photostimulated reaction of anions 1, 2, and 3 with 1-bromonaphthalene (4) after quenching with MeI renders 1-(methylthio)naphthalene (6) as a main product together with bis(1-naphthyl) sulfide (7) and naphthalene (5). The thioacetate ion (2) and thiobenzoate ion (3) were unreactive toward 4 as electron-donor under photostimulation; however, in the presence of potassium tert-butoxide anion (entrainment conditions), they gave the mentioned products 5, 6, and 7, after the addition of MeI. Quenching of the triplet state of 4 was assigned as the photoinduced initiation step, with a rate constant value of (4.6+/-0.5)x10(8) M-1 s-1 for tert-butoxide anion and a rough estimated value of (8+/-7)x10(7) M-1 s-1 for anion 1. By using hydrogen abstraction from DMSO as the competitive reaction, the absolute rate constants for the addition of anions 1, 2, and 3 to 1-naphthyl radicals have been determined to be 1.0x10(9), 1.2x10(9), and 3.5x10(9) M-1 s-1, respectively. This reactivity order is in agreement with the stability of the resulting radical anions (ArNu)*- (10-12)*-. The inhibition experiments of the photoinduced substitution reaction in the presence of radical scavengers and the global quantum yield higher than the unity are evidence of a radical chain mechanism for these substitution reactions by anions 1 and 2. Anion 3 adds to the 1-naphthyl radical, but is neither able to initiate nor to keep the propagation cycle. Evaluation of the electron-transfer driving forces for the reaction between (ArNu)*- and 4 together with the absence of a chain reaction for the anion 3 indicate that the propagation in the proposed mechanism is given by an acid-base reaction between the radical .C(O)Me or .C(NH)NH2 (13) and a base.     

Kinetic study of IO radical with RO2 (R = CH(3), C2H5, and CF3) using cavity ring-down spectroscopy

The reactions of iodine monoxide radical, IO, with alkyl peroxide radicals, RO(2) (R = CH(3), C(2)H(5), and CF(3)), have been studied using cavity ring-down spectroscopy. The rate constant of the reaction of IO with CH(3)O(2) was determined to be (7.0 +/- 3.0) x 10(-11) cm(3) molecule(-1) s(-1) at 298 K and 100 Torr of N(2) diluent. The quoted uncertainty is two standard deviations. No significant pressure dependence of the rate constant was observed at 30-130 Torr total pressure of N(2) diluent. The temperature dependence of the rate constants was also studied at 213-298 K. The upper limit of the branching ratio of OIO radical formation from IO + CH(3)O(2) was estimated to be <0.1. The reaction rate constants of IO + C(2)H(5)O(2) and IO + CF(3)O(2) were determined to be (14 +/- 6) x 10(-11) and (6.3 +/- 2.7) x 10(-11) cm(3) molecule(-1) s(-1) at 298 K, 100 Torr of N(2) diluent, respectively. The upper limit of the reaction rate constant of IO with CH(3)I was <4 x 10(-14) cm(3) molecule(-1) s(-1).     

Kinetic and product study of the gas-phase reactions of OH radicals, NO(3) radicals, and O(3) with (C(2)H(5)O)(2)P(S)CH(3) and (C(2)H(5)O)(3)PS

Rate constants for the reactions of OH radicals and NO3 radicals with O,O-diethyl methylphosphonothioate [(C(2)H(5)O)(2)P(S)CH(3); DEMPT] and O,O,O-triethyl phosphorothioate [(C(2)H(5)O)(3)PS; TEPT] have been measured using relative rate methods at atmospheric pressure of air over the temperature range 296-348 K for the OH radical reactions and at 296 +/- 2 K for the NO(3) radical reactions. At 296 +/- 2 K, the rate constants obtained for the OH radical reactions (in units of 10(-11) cm(3) molecule(-1) s(-1)) were 20.4 +/- 0.8 and 7.92 +/- 0.27 for DEMPT and TEPT, respectively, and those for the NO(3) radical reactions (in units of 10(-15) cm(3) molecule(-1) s(-1)) were 2.01 +/- 0.20 and 1.03 +/- 0.10, respectively. Upper limits to the rate constants for the reactions of O(3) with DEMPT and TEPT of <6 x 10(-20) cm(3) molecule(-1) s(-1) were determined in each case. Rate constants for the OH radical reactions, measured relative to k(OH + alpha-pinene) = 1.21 x 10(-11) e(436/T) cm(3) molecule(-1) s(-1), resulted in the Arrhenius expressions k(OH + DEMPT) = 1.08 x 10(-11) e(871+/-25)/T cm(3) molecule(-1) s(-1) and k(OH + TEPT) = 8.21 x 10(-13) e(1353+/-49)/T cm(3) molecule(-1) s(-1) over the temperature range 296-348 K, where the indicated errors are two least-squares standard deviations and do not include the uncertainties in the reference rate constant. Diethyl methylphosphonate was identified and quantified from the OH radical and NO(3) radical reactions with DEMPT, with formation yields of 21 +/- 4%, independent of temperature, from the OH radical reaction and 62 +/- 11% from the NO(3) radical reaction at 296 +/- 2 K. Similarly, triethyl phosphate was identified and quantified from the OH radical and NO(3) radical reactions with TEPT, with formation yields of 56 +/- 9%, independent of temperature, from the OH radical reaction and 78 +/- 15% from the NO(3) radical reaction at 296 +/- 2 K.     

Kinetics of radical heterolysis reactions forming alkene radical cations

Rate constants for heterolytic fragmentation of beta-(ester)alkyl radicals were determined by a combination of direct laser flash photolysis studies and indirect kinetic studies. The 1,1-dimethyl-2-mesyloxyhexyl radical (4a) fragments in acetonitrile at ambient temperature with a rate constant of k(het) > 5 x 10(9) s(-1) to give the radical cation from 2-methyl-2-heptene (6), which reacts with acetonitrile with a pseudo-first-order rate constant of k = 1 x 10(6) s(-1) and is trapped by methanol in acetonitrile in a reversible reaction. The 1,1-dimethyl-2-(diphenylphosphatoxy)hexyl radical (4b) heterolyzes in acetonitrile to give radical cation 6 in an ion pair with a rate constant of k(het) = 4 x 10(6) s(-1), and the ion pair collapses with a rate constant of k < or = 1 x 10(9) s(-1). Rate constants for heterolysis of the 1,1-dimethyl-2-(2,2-diphenylcyclopropyl)-2-(diphenylphosphatoxy)ethyl radical (5a) and the 1,1-dimethyl-2-(2,2-diphenylcyclopropyl)-2-(trifluoroacetoxy)ethyl radical (5b) were measured in various solvents, and an Arrhenius function for reaction of 5a in THF was determined (log k = 11.16-5.39/2.3RT in kcal/mol). The cyclopropyl reporter group imparts a 35-fold acceleration in the rate of heterolysis of 5a in comparison to 4b. The combined results were used to generate a predictive scale for heterolysis reactions of alkyl radicals containing beta-mesyloxy, beta-diphenylphosphatoxy, and beta-trifluoroacetoxy groups as a function of solvent polarity as determined on the E(T)(30) solvent polarity scale.     

Hydrogen abstraction from deoxyribose by a neighbouring uracil-5-yl radical

Hydrogen abstraction from the C1' and C2' positions of deoxyadenosine by a neighbouring uracil-5-yl radical in the 5'-AU*-3' DNA sequence is explored using DFT. This hydrogen abstraction is the first step in a sequence leading to single or double strand break in DNA. The uracil-5-yl radical can be the result of photolysis or low-energy electron (LEE) attachment. If the radical is produced by photolysis the neighbouring adenine will become a cation radical and if it is produced by LEE the adenine will remain neutral. The hydrogen abstraction reactions for both cases were investigated. It is concluded that it is possible for the uracil-5-yl to abstract hydrogen from C1' and C2'. When adenine is neutral there is a preference for the C1' site and when the adenine is a radical cation the C2' site is the preferred. If adenine is positively charged, the rate-limiting step when abstracting hydrogen from C1' is the formation of an intermediate crosslink between uracil and adenine. This crosslink might be avoided in dsDNA, making C1' the preferred site for abstraction.     

Formation of spectral intermediate G-C and A-T anion complex in duplex DNA studied by pulse radiolysis

The dynamics of electron adducts of 2'-deoxynucleotides and oligonucelotides (ODNs) were measured spectroscopically by nanosecond pulse radiolysis. The radical anions of the nucleotides were produced within 10 ns by the reaction of hydrated electrons (e(aq)(-)) and were protonated to form the corresponding neutral radicals. At pH 7.0, the radical anion of deoxythymidine (dT(*-)) was protonated to form the neutral radical dT(H)(*) in the time range of microseconds. The rate constant for the protonation was determined as 1.8 x 10(10) M(-1) s(-1). In contrast, the neutral radical of dC(H)(*) was formed immediately after the pulse, suggesting that the protonation occurs within 10 ns. The transient spectra of excess electrons of the double-stranded ODNs 5'-TAATTTAATAT-3' (AT) and 5'-CGGCCCGGCGC-3' (GC) differed from those of pyrimidine radicals (C and T) and their composite. In contrast, the spectra of the electron adducts of the single-stranded ODNs GC and AT exhibited characteristics of C and T, respectively. These results suggest that, in duplex ODNs, the spectral intermediates of G-C and A-T anions complex were formed. On the microsecond time scale, the subsequent changes in absorbance of the ODN AT had a first-order rate constant of 4 x 10(4) s(-1), reflecting the protonation of T.     

New insight into solvent effects on the formal HOO. + HOO. reaction

The 2,2'-azobis(isobutyronitrile)(AIBN)-induced autoxidation of gamma-terpinene (TH) at 50 degrees C produces p-cymene and hydrogen peroxide in a radical-chain reaction having HOO* as one of the chain-carrying radicals. The kinetics of this reaction in cyclohexane and tert-butyl alcohol show that chain termination involves the formal HOO. + HOO. self-reaction over a wide range of gamma-terpinene, AIBN, and O2 concentrations. However, in acetonitrile this termination process is accompanied by termination via the cross-reaction of the terpinenyl radical, T., with the HOO. radical under conditions of relatively high [TH] (140-1000 mM) and low [O2] (2.0-5.5 mM). This is because the formal HOO. + HOO. reaction is comparatively slow in acetonitrile (2k approximately 8 x 10(7) M(-1) s(-1)), whereas, this reaction is almost diffusion-controlled in tert-butyl alcohol and cyclohexane, 2k approximately 6.5 x 10(8) and 1.3 x 10(9) M(-1) s(-1), respectively. Three mechanisms for the bimolecular self-reaction of HOO. radicals are considered: 1) a head-to-tail hydrogen-atom transfer from one radical to the other, 2) a head-to-head reaction to form an intermediate tetroxide, and 3) an electron-transfer between HOO. and its conjugate base, the superoxide radical anion, O2-.. The rate constant for reaction by mechanism (1) is shown to be dependent on the hydrogen bond (HB) accepting ability of the solvent; that by mechanism (2) is shown to be too slow for this process to be of any importance; and that by mechanism (3) is dependent on the pH of the solvent and its ability to support ionization. Mechanism (3) was found to be the main termination process in tert-butyl alcohol and acetonitrile. In the gas phase, the rate constant for the HOO. + HOO. reaction (mechanism (1)) is about 1.8 x 10(9) M(-1) s(-1) but in water at pH< or =2 where the ionization of HOO. is completely suppressed, this rate constant is only 8.6 x 10(5) M(-1) s(-1). The very large retarding effect of water on this reaction has not previously been explained. We find that it can be quantitatively accounted for by using Abraham's HB acceptor parameter, beta(2)(H), for water of 0.38 and an estimated HB donor parameter, alpha(2)(H), for HOO. of about 0.87. These Abraham parameters allow us to predict a rate constant for the HOO. + HOO. reaction in water at 25 degrees C of 1.2 x 10(6) M(-1) s(-1) in excellent agreement with experiment.