Dynamics and Multiconfiguration Potential Energy Surface for the Singlet O₂ Reactions with Radical Cations of Guanine, 9-Methylguanine, 2′-Deoxyguanosine, and Guanosine

Abstract

Reactions of electronically excited singlet oxygen ( 1 O 2 ) with the radical cations of guanine (9HG •+ ), 9-methylguanine (9MG •+ ), 2′-deoxyguanosine (dGuo •+ ), and guanosine (Guo •+ ) were studied in the gas phase by a combination of guided-ionbeam mass spectrometric measurement of product ions and cross sections as a function of collision energy (E col ) and electronic structure calculations of the reaction potential energy surface (PES) at various levels of theory. No product could be captured in the 1 O 2 reaction with bare 9HG •+ or 9MG •+ , because energized products decayed rapidly to reactants before being detected. To overcome this unfavorable kinetics, monohydrated 9HG •+ •H 2 O and 9MG •+ •H 2 O were used as reactant ions, of which the peroxide product ions were stabilized by energy relaxation via elimination of the water ligand. Reaction cross sections for 9HG •+ •H 2 O and 9MG •+ • H 2 O decrease with increasing E col , becoming negligible above 0.6 eV. This indicates that the reactions are exothermic with no barriers above reactants and the heat of formation of the products is sufficiently large to overcome their water ligand elimination energy (0.7 eV). Peroxide product ions were also detected in the 1 O 2 reactions with unhydrated dGuo •+ and Guo •+ , in which intramolecular vibrational redistribution was able to stabilize oxidation products. 9MG •+ was utilized as a model system to explore the reaction PES for the initial 1 O 2 addition to the guanine radical cation. Calculations were carried out using single-reference ωB97XD, RI-MP2, and DLPNO-CCSD(T) and multireference CASSCF and CASPT2. Although the same PES profile was obtained at different levels of theory, the energies of the mixed open-and closed-shell 1 O 2 reactant and the open-shell reaction intermediates, transition states, and products are sensitive to the theories. By taking into account both static and dynamic electron correlations, the CASPT2 PES has provided the best agreement with the experimentally measured reaction thermodynamics and predicted 8peroxide as the most probable initial oxidation product of the guanine radical cation.

Singlet Oxygen Oxidation of the Radical Cations of 8‐Oxo‐2′‐deoxyguanosine and Its 9‐Methyl Analogue: Dynamics, Potential Energy Surface, and Products Mediated by C5‐O2‐Addition

“…The relatively lower reaction efficiency of OG .+ might be attributed to the quenching of 1 O 2 by its sugar group. A similar extent of reaction inhibition by the sugar group was observed in the 1 O 2 reactions with the radical cations of 2′‐deoxyguanosine and guanosine, [28h] where the efficiencies of the two nucleosides are only half compared to the radical cations of guanine and 9‐methylguanine, albeit that all of the reactant ions presented the same E col dependence.…”

“…According to our recent work, [28h] the maximum 1 O 2 reaction efficiencies with the radical cations of 9‐methylguanine and 2′‐deoxyguanosine are 1.4 % and 0.7 %, respectively (both were observed at E col =0.05–0.1 eV). Therefore, the 1 O 2 oxidation efficiencies of 9MOG .+ and OG .+ are a factor of two higher than those of the radical cations of 9‐methylguanine and 2′‐deoxyguanosine.…”

“…The O′Hair [28a,b,32] and Bohme [28c] laboratories extended this approach to the formation of guanosine radical cations via collision‐induced dissociation (CID) of Cu(II)‐nucleoside(G) complexes wherein the redox separation of [Cu II G 3 ] .2+ leads to the formation of complementary product ions G .+ and [Cu I G 2 ] + . This method was successfully used to generate the radical cations of guanine, 9‐methylguanine, 2′‐deoxyguanosine and guanosine, [28h,33] as well as those of Hachimoji nucleobases [28e–g] . In the present work, 9MOG .+ was generated by CID of the [Cu II (9MOG) 3‐n (2′‐deoxyguanosine) n ] .2+ (n=0–2) complexes which were formed by electrospray ionization (ESI) of a methanol/water solution containing equimolar concentration of 9MOG, 2′‐deoxyguanosine (used as a co‐ligand) and Cu(NO 3 ) 2 .…”

“…Note that, due to the mixed open‐ and closed‐shell character of 1 O 2 , [46] single Slater‐determinant wavefunctions may not accurately describe the electronic structures of 1 O 2 and its reaction adducts [28h] . To verify whether the reaction structures are dominated by single‐determinant wavefunctions, T1 diagnostic [47] was performed using DLPNO‐CCSD(T)/aug‐cc‐pVTZ and the results are included in Table S1.…”

“…Note that the CASSCF calculations included primarily nondynamic electronic correlation. It is not unusual that CASSCF may have overestimated reaction energies and activation barrier heights, as revealed in the experimental and computational study of the 1 O 2 oxidation of neutral guanine [50] and 9MG .+ [28h] …”