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Wereport an in-depth study on the gas-phase reactions of singletO2[a1Δg] with methionine (Met)at different ionization and hydration states (including deprotonated[Met – H]−, hydrated deprotonated [Met –H]−(H2O)1,2, and hydratedprotonated MetH+(H2O)1,2), usingguided-ion-beam scattering mass spectrometry. The measurements includethe effects of collision energy (Ecol)on reaction cross sections over a center-of-mass Ecolrange from 0.05 to 1.0 eV. The aim of this study isto probe the influences of Met ionization and hydration on its oxidationmechanism and dynamics. Density functional theory calculations, Rice-Ramsperger-Kassel-Marcusmodeling, and quasi-classical, direct dynamics trajectory simulationswere performed to examine the properties of various complexes andtransition states that might be important along reaction coordinates,probe reaction potential energy surfaces, and to establish the atomic-levelmechanism for the Met oxidation process. No oxidation products wereobserved for the reaction of [Met – H]−with 1O2due to the high-energy barriers located in theproduct channels for this system. However, this nonreactive propertywas altered by the microsolvation of [Met – H]−; as a result, hydroperoxides were captured as the oxidation productsfor [Met – H]−(H2O)1,2+ 1O2. For the reaction of MetH+(H2O)1,2+ 1O2, besidesformation of hydroperoxides, an H2O2eliminationchannel was observed. The latter channel is similar to what was foundin the reaction of dehydrated MetH+with 1O2(J. Phys. Chem. B2011, 115, 2671). The reactions of hydrated protonated and deprotonatedMet are all inhibited by Ecol, becomingnegligible at Ecol≥ 0.5 eV. Thekinetic and dynamical consequences of microsolvation on Met oxidationand their biological implications are discussed. [ABSTRACT FROM AUTHOR]

In DNA, guanine is the most susceptible to oxidative damage by exogenously and endogenously produced electronically excited singlet oxygen ( 1 O 2 ). The reaction mechanism and the product outcome strongly depend on the nucleobase ionization state and structural context. Previously, exposure of a monomeric 9-methylguanine radical cation (9MG •+ , a model guanosine compound) to 1 O 2 was found to result in the formation of an 8-peroxide as the initial product. The present work explores the 1 O 2 oxidation of 9MG •+ and its dehydrogenated neutral form [9MG - H] • within a Watson-Crick base pair consisting of one-electron-oxidized 9-methylguanine-1-methylcytosine [9MG·1MC] •+ . Emphasis is placed on entangling the base pair structural context and intra-base pair proton transfer with and consequences thereof on the singlet oxygenation of guanine radical species. Electrospray ionization coupled with guided-ion beam tandem mass spectrometry was used to study the formation and reaction of guanine radical species in the gas phase. The 1 O 2 oxidation of both 9MG •+ and [9MG - H] • is exothermic and proceeds barrierlessly either in an isolated monomer or within a base pair. Single- and multi-referential theories were tested for treating spin contaminations and multi-configurations occurring in radical- 1 O 2 interactions, and reaction potential energy surfaces were mapped out to support experimental findings. The work provides a comprehensive profile for the singlet oxygenation of guanine radicals in different charge states and in the absence and the presence of base pairing. All results point to an 8-peroxide as the major oxidation product in the experiment, and the oxidation becomes slightly more favorable in a neutral radical form. On the basis of a variety of reaction pathways and product profiles observed in the present and previous studies, the interplay between guanine structure, base pairing, and singlet oxygenation and its biological implications are discussed.

Direct dynamics simulations of HNO 3 with dicyanamide anion DCA - ( i.e. , N(CN) 2 - ) and dicyanoborohydride anion DCBH - ( i.e. , BH 2 (CN) 2 - ) were performed at the B3LYP/6-31+G(d) level of theory in an attempt to elucidate the primary and secondary reactions in the two reaction systems. Guided by trajectory results, reaction coordinates and potential energy diagrams were mapped out for the oxidation of DCA - and DCBH - by one and two HNO 3 molecules, respectively, in the gas-phase and in the condensed-phase ionic liquids using the B3LYP/6-311++G(d,p) method. The oxidation of DCA - by HNO 3 is initiated by proton transfer. The most important pathway leads to the formation of O 2 N-NHC(O)NCN - , and the latter reacts with a second HNO 3 to produce O 2 N-NHC(O)NC(O)NH-NO 2 - (DNB - ). The oxidation of DCBH - by HNO 3 may follow a similar mechanism as that of DCA - , producing two analogue products: O 2 N-NHC(O)BH 2 CN - and O 2 N-NHC(O)BH 2 C(O)NH-NO 2 - . Moreover, two new, unique reaction pathways were discovered for DCBH - because of its boron-hydride group: (1) isomerization of DCBH - to CNBH 2 CN - and CNBH 2 NC - and (2) H 2 elimination in which the proton in HNO 3 combines with a hydride-H in DCBH - . The Rice-Ramsperger-Kassel-Marcus (RRKM) theory was utilized to calculate reaction kinetics and product branching ratios. The RRKM results indicate that the formation of DNB - is exclusively important in the oxidation of DCA - , whereas the same type of reaction is a minor channel in the oxidation of DCBH - . In the latter case, H 2 elimination becomes dominating. The RRKM modeling also indicates that the oxidation rate constant of DCBH - is higher than that of DCA - by an order of magnitude. This rationalizes the enhanced preignition performance of DCBH - over DCA - with HNO 3 .

Direct dynamics trajectory simulations were carried out for the NO 2 oxidation of 1-ethyl-3-methylimidazolium dicyanamide (EMIM + DCA - ), which were aimed at probing the nature of the primary and secondary reactions in the system. Guided by trajectory results, reaction coordinates and potential energy diagrams were mapped out for NO 2 with EMIM + DCA - , as well as with its analogues 1-butyl-3-methylimidazolium dicyanamide (BMIM + DCA - ) and 1-allyl-3-methylimidazolium dicyanamide (AMIM + DCA - ). Reactions of the dialkylimidazolium-dicyanamide (DCA) ionic liquids (ILs) are all initiated by proton transfer and/or alkyl abstraction between 1,3-dialkylimidazolium cations and DCA - anion, of which two exoergic pathways are particularly relevant to their oxidation activities. One pathway is the transfer of a H β -proton from the ethyl, butyl, or allyl group of the dialkylimidazolium cation to DCA - that results in the concomitant elimination of the corresponding alkyl as a neutral alkene, and the other pathway is the alkyl abstraction by DCA - via a second order nucleophilic substitution (SN 2 ) mechanism. The intra-ion-pair reaction products, including [dialkylimidazolium + - H C2 + ], alkylimidazole, alkene, alkyl-DCA, HDCA, and DCA - , react with NO 2 ) complexes, albeit the two complex structures have similar formation energies. The exoergic intra-ion-pair reactions in the dialkylimidazolium-DCA ILs account for their significantly higher oxidation activities over the previously reported 1-methyl-4-amino-1,2,4-triazolium dicyanamide [Liu, J.; 2 ) complexes, albeit the two complex structures have similar formation energies. The exoergic intra-ion-pair reactions in the dialkylimidazolium-DCA ILs account for their significantly higher oxidation activities over the previously reported 1-methyl-4-amino-1,2,4-triazolium dicyanamide [Liu, J.; J. Phys. Chem. B 2019, 123, 2956-2970] and for the relatively higher reactivity of BMIM + DCA - vs AMIM + DCA - as BMIM + has a higher reaction path degeneracy for intra-ion-pair H β -proton transfer and its H β -transfer is more energetically favorable. To validate and directly compare our computational results with spectral measurements in the ILs, infrared and Raman spectra of BMIM + DCA - and AMIM + DCA - and their products with NO 2 were calculated using an ionic liquid solvation model. The simulated spectra reproduced all of the vibrational frequencies detected in the reactions of BMIM + DCA - and AMIM + DCA - IL droplets with NO 2 (as reported by Brotton et al. [ J. Phys. Chem. A 2018, 122, 7351-7377] and Lucas et al. [ J. Phys. Chem. A 2019, 123, 400-416]).

We report a kinetics and mechanistic study on the 1 O 2 oxidation of 9-methylguanine (9MG) and the cross-linking of the oxidized intermediate 2-amino-9-methyl-9 H -purine-6,8-dione (9MOG OX ) with N α -acetyl-lysine-methyl ester (abbreviated as LysNH 2 ) in aqueous solutions of different pH. Experimental measurements include the determination of product branching ratios and reaction kinetics using mass spectrometry and absorption spectroscopy, and the characterization of product structures by employing collision-induced dissociation. Strong pH dependence was revealed for both 9MG oxidation and the addition of nucleophiles (water and LysNH 2 ) at the C5 position of 9MOG OX . The 1 O 2 oxidation rate constant of 9MG was determined to be 3.6 × 10 7 M -1 ·s -1 at pH 10.0 and 0.3 × 10 7 M -1 ·s -1 at pH 7.0, both of which were measured in the presence of 15 mM LysNH 2 . The ωB97XD density functional theory coupled with various basis sets and the SMD implicit solvation model was used to explore the reaction potential energy surfaces for the 1 O 2 oxidation of 9MG and the formation of C5-water and C5-LysNH 2 adducts of 9MOG OX . Computational results have shed light on reaction pathways and product structures for the different ionization states of the reactants. The present work has confirmed that the initial 1 O 2 addition represents the rate-limiting step for the oxidative transformations of 9MG. All of the downstream steps are exothermic with respect to the starting reactants. The C5-cross-linking of 9MOG OX with LysNH 2 significantly suppressed the formation of spiroiminodihydantoin (9MSp) resulting from the C5-water addition. The latter became dominant only at the low concentration (∼1 mM) of LysNH 2 .

Direct dynamics trajectories were calculated at the B3LYP/6-31G(d) level of theory in an attempt to understand the reaction of 1-methyl-4-amino-1,2,4-triazolium dicyanamide (MAT + DCA - ) with NO 2 . The trajectories revealed an extensive intra-ion-pair proton transfer in MAT + DCA - . The reaction pathways of the ensuing HDCA (i.e., HNCNCN) and [MAT + - H C5 + ] (i.e., deprotonated at C5-H of MAT + ) molecules as well as DCA - with NO 2 were identified. The reaction of NO 2 with HDCA and DCA - produces HNC(-ONO)NCN and NCNC(-ONO)N - or NCNCN-NO 2 - , respectively, whereas that with [MAT + - H C5 + ] results in the formation of 5-O-MAT (i.e., 4-amino-2-methyl-2,4-dihydro-3 H-1,2,4-triazo-3-one) + NO and [MAT + - H 2 + ] + HNO 2 . Using trajectories for guidance, structures of intermediates, transition states and products, and the corresponding reaction potential surfaces were elucidated at B3LYP/6-311++ G(d,p). Rice-Ramsperger-Kassel-Marcus (RRKM) theory was utilized to calculate the reaction rates and statistical product branching ratios. A comparison of direct dynamics simulations with RRKM modeling results indicate that the reactions of NO 2 with HDCA and DCA - are nonstatistical. To validate our computational results, infrared and Raman spectra of MAT + DCA - and its reaction products with NO 2 were calculated using an ionic liquid solvation model. The calculated spectra reproduced the vibrational frequencies detected in an earlier spectroscopic study of MAT + DCA - droplets with NO 2 [ Brotton , S. J. ; J. Phys. Chem. Lett. 2017 , 8 , 6053 ].

We report a kinetic and mechanistic study on the title reactions, in which 1 O 2 was generated by the reaction of H 2 O 2 with Cl 2 and bubbled into an aqueous solution of guanine and 9-methylguanine (9MG) at different pH values. Oxidation kinetics and product branching ratios were measured using online electrospray ionization mass spectrometry coupled with absorption and emission spectrophotometry, and product structures were determined by collision-induced dissociation (CID) tandem mass spectrometry. Experiments revealed strong pH dependence of the reactions. The oxidation of guanine is noticeable only in basic solution, while the oxidation of 9MG is weak in acidic solution, increases in neutral solution, and becomes intensive in basic solution. 5-Guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) were detected as the major oxidation products of guanine and 9MG, and Sp became dominant in basic solution. A reaction intermediate was captured in mass spectra, and assigned to gem-diol on the basis of CID measurements. This intermediate served as the precursor for the formation of Gh. After taking into account solution compositions at each pH, first-order oxidation rate constants were extracted for individual species: that is, 3.2-3.6 × 10 7 M -1 s -1 for deprotonated guanine, and 1.2 × 10 6 and 4.6-4.9 × 10 7 M -1 s -1 for neutral and deprotonated 9MG, respectively. Guided by approximately spin-projected density-functional-theory-calculated reaction potential energy surfaces, the kinetics for the initial 1 O 2 addition to guanine and 9MG was evaluated using transition state theory (TST). The comparison between TST modeling and experiment confirms that 1 O 2 addition is rate-limiting for oxidation, which forms endoperoxide and peroxide intermediates as determined in previous measurements of the same systems in the gas phase.

The reactivity of cystine toward electronically excited singlet O 2 (a 1 Δ g ) has been long debated, despite the fact that most organic disulfides are susceptible to oxidation by singlet O 2 . We report a combined experimental and computational study on reactions of singlet O 2 with gas-phase cystine at different ionization and hydration states, aimed to determine reaction outcomes, mechanisms, and potential energy surfaces (PESs). Ion-molecule collisions of protonated and di-deprotonated cystine ions with singlet O 2 , in both the absence and the presence of a water ligand, were measured over a center-of-mass collision energy (E col ) range from 0.1 to 1.0 eV, using a guided-ion-beam scattering tandem mass spectrometer. No oxidation was observed for these reactant ions except collision-induced dissociation at high energies. Guided by density functional theory (DFT)-calculated PESs, reaction coordinates were established to unravel the origin of the nonreactivity of cystine ions toward singlet O 2 . To account for mixed open- and closed-shell characters, singlet O 2 and critical structures along reaction coordinates were evaluated using broken-symmetry, open-shell DFT with spin contamination errors removed by an approximate spin-projection method. It was found that collision of protonated cystine with singlet O 2 follows a repulsive potential surface and possesses no chemically significant interaction and that collision-induced dissociation of protonated cystine is dominated by loss of water and CO. Collision of di-deprotonated cystine with singlet O 2 , on the other hand, forms a short-lived electrostatically bonded precursor complex at low E col . The latter may evolve to a covalently bonded persulfoxide, but the conversion is blocked by an activation barrier lying 0.39 eV above reactants. At high E col , C-S bond cleavage dominates the collision-induced dissociation of di-deprotonated cystine, leading to charge-separated fragmentation. Cross section for the ensuing fragment ion H 2 NCH(CO 2 - )CH 2 SS • was measured as a function of E col , and the mechanism of charge-separated fragmentation was discussed. It was also found that the reaction of deprotonated cystine with singlet O 2 follows a similar mechanism as that of di-deprotonated cystine, but with an even higher activation barrier (0.72 eV).

8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is one of the most common DNA lesions resulting from reactive oxygen species and ionizing radiation, and is involved in mutagenesis, carcinogenesis, and cell death. Notably, 8-oxodGuo is more reactive toward singlet (a 1 Δ g ) O 2 than the undamaged guanosine, and the lesions arising from the secondary oxidation of 8-oxodGuo are more mutagenic. Herein the 1 O 2 oxidation of free base 8-oxoguanine (8-oxoG) was investigated at different initial conditions including protonated [8-oxoG + H] + , deprotonated [8-oxoG - H] - , and their monohydrates. Experiment was carried out on a guided-ion beam scattering tandem mass spectrometer. Measurements include the effects of collision energy (E col ) on reaction cross sections over a center-of-mass E col range from 0.1 to 0.5 eV. The aim of this study is to quantitatively probe the sensitivity of the early stage of 8-oxoG oxidation to ionization and hydration. Density functional theory and Rice-Ramsperger-Kassel-Marcus calculations were performed to identify the intermediates and the products along reaction pathways and locate accessible reaction potential energy surfaces, and to rationalize reaction outcomes from energetic and kinetic points of view. No product was observed for the reaction of [8-oxoG + H] + ·W 0,1 (W = H 2 O) because insurmountable barriers block the addition of 1 O 2 to reactant ions. Neither was [8-oxoG - H] - reactive with 1 O 2 , in this case due to the rapid decay of transient intermediates to starting reactants. However, the nonreactivity of [8-oxoG - H] - was inverted by hydration; as a result, 4,5-dioxetane of [8-oxoG - H] - was captured as the main oxidation product. Reaction cross section for [8-oxoG - H] - ·W + 1 O 2 decreases with increasing E col and becomes negligible above 0.3 eV, indicating that the reaction is exothermic and has no barriers above reactants. The contrasting oxidation behaviors of [8-oxoG + H] + ·W 0,1 and [8-oxoG - H] - ·W 0,1 , which are relevant to the pH dependence of 8-oxoG oxidation in solution, are interpreted in terms of different 1 O 2 addition pathways.

It has been proposed (J. Phys. Chem. B 2011, 115, 2671) that the ammonium group is involved in the gas-phase reaction of protonated methionine (MetH(+)) with singlet oxygen (1)O2, yielding hydrogen peroxide and a dehydro compound of MetH(+) where the -NH3(+) transforms into cyclic -NH2-. For the work reported, the gas-phase reaction of protonated N-acetylmethionine (Ac-MetH(+)) with (1)O2 was examined, including the measurements of reaction products and cross sections over a center-of-mass collision energy (Ecol) range from 0.05 to 1.0 eV using a guided-ion-beam apparatus. The aim is to probe how the acetylation of the ammonium group affects the oxidation chemistry of the ensuing Ac-MetH(+). Properties of intermediates, transition states, and products along the reaction coordinate were explored using density functional theory calculations and Rice-Ramsperger-Kassel-Marcus (RRKM) modeling. Direct dynamics trajectory simulations were carried out at Ecol of 0.05 and 0.1 eV using the B3LYP/4-31G(d) level of theory. In contrast to the highly efficient reaction of MetH(+) + (1)O2, the reaction of Ac-MetH(+) + (1)O2 is extremely inefficient, despite there being exoergic pathways. Two product channels were observed, corresponding to transfer of two H atoms from Ac-MetH(+) to (1)O2 (H2T), and methyl elimination (ME) from a sulfone intermediate complex. Both channels are inhibited by collision energies, becoming negligible at Ecol > 0.2 eV. Analysis of RRKM and trajectory results suggests that a complex-mediated mechanism might be involved at very low Ecol, but direct, nonreactive collisions prevail over the entire Ecol range and physical quenching of (1)O2 occurs during the early stage of collisions.

We present a study on the gas-phase reaction of deprotonated cysteine with the lowest electronically excited state of molecular oxygen O2[a(1)Δg], including the measurement of the effects of collision energy (E(col)) on reaction cross sections over a center-of-mass E(col) range from 0.1 to 1.0 eV. Deprotonated cysteine was generated using electrospray ionization, and has a carboxylate anionic structure (HSCH2CH(NH2)CO2(-)) in the gas phase. Three product ion channels were observed. The dissociation of HSCH2CH(NH2)CO2(-) to NH2CH2CO2(-) and neutral CH2S has the largest cross section over the entire E(col) range. This product channel is driven by the electronic excitation energy of (1)O2 (the so-called dissociative excitation transfer), and is strongly suppressed by E(col). Two minor channels correspond to the formation of HSCH2C(NH)CO2(-) + H2O2 via abstraction of two hydrogen atoms from HSCH2CH(NH2)CO2(-) by (1)O2, and the formation of OSCH2CH(NH2)CO2(-) radical via elimination of ·OH from an intermediate complex, respectively. Density functional theory calculations were used to locate various complexes, transition states, and products. Quasi-classical direct dynamics trajectory simulations were carried out at E(col) = 0.2 eV using the B3LYP/4-31G(d) level of theory. Trajectory results were used to guide the construction of a reaction coordinate, discriminate between different mechanisms, and provide additional mechanistic insights. Analysis of trajectories highlights the importance of complex mediation at the early stages of all reactions, and suggests a partially concerted mechanism for H2O2 elimination.

The reactions of deprotonated tyrosine ([Tyr-H](-)) and tryptophan ([Trp-H](-)) with the lowest electronically excited state of molecular oxygen O(2)[a(1)Δ(g)] have been studied in the gas phase, including the measurement of the effects of collision energy (E(col)) on reaction cross sections over a center-of-mass E(col) range from 0.05 to 1.0 eV. [Tyr-H](-) and [Trp-H](-) were generated using electrospray ionization, and both have a pure carboxylate anion structure in the gas phase. Density functional theory calculations and RRKM modeling were used to examine properties of various complexes, transition states, and products that might be important along the reaction coordinate. It was found that deprotonation of Tyr and Trp results in a large effect on their (1)O(2)-mediated oxidation. For [Tyr-H](-), the reaction corresponds to the formation of a hydroperoxide intermediate, followed by intramolecular H transfer and subsequent dissociation to product ion 4-(2-aminovinyl)phenolate, and neutral H(2)O(2) and CO(2). Despite that the reaction is 1.83 eV exothermic, the reaction cross section shows a threshold-like behavior at low E(col) and increases with increasing E(col), suggesting that the reaction bears an activation barrier above the reactants. Quasi-classical, direct dynamics trajectory simulations were carried out for [Tyr-H](-) + (1)O(2) at E(col) = 0.75 eV, using B3LYP/4-31G* level of theory. Trajectories demonstrated the intermediacy of complexes at the early stage of the reaction. A similar product channel was observed in the reaction of [Trp-H](-) with (1)O(2), yielding product ion 3-(2-aminovinyl)indol-1-ide, H(2)O(2) and CO(2). However, the reaction cross section of [Trp-H](-) is strongly suppressed by E(col) and becoming negligible at E(col) > 1.0 eV, indicating that this reaction proceeds without energy barriers above the reactants.

The reaction of protonated methionine with the lowest electronically excited state of molecular oxygen O(2)(a(1)Δ(g)) was studied in a guided ion beam apparatus, including the measurement of reaction cross sections over a center-of-mass collision energy (E(col)) range of 0.1-2.0 eV. A series of electronic structure and RRKM calculations were used to examine the properties of various complexes and transition states that might be important along the reaction coordinate. Only one product channel is observed, corresponding to generation of hydrogen peroxide via transfer of two hydrogen atoms (H2T) from protonated methionine to singlet oxygen. At low collision energies, the reaction approaches the collision limit and may be mediated by intermediate complexes. The reaction shows strong inhibition by collision energy, and becomes negligible at E(col) > 1.25 eV. A large set of quasi-classical direct dynamics trajectory simulations were calculated at the B3LYP/6-21G level of theory. Trajectories reproduced experimental results and provided insight into the mechanistic origin of the H2T reaction, how the reaction probability varies with impact parameter, and the suppressing effect of collision energy. Analysis of the trajectories shows that at E(col) = 1.0 eV the reaction is mediated by a precursor and/or hydroperoxide complex, and is sharply orientation-dependent. Only 20% of collisions have favorable reactant orientations at the collision point, and of those, less than half form precursor and hydroperoxide complexes which eventually lead to reaction. The narrow range of reactive collision orientations, together with physical quenching of (1)O(2) via intersystem crossing between singlet and triplet electronic states, may account for the low reaction efficiency observed at high E(col)., (© 2011 American Chemical Society)