Cation Radicals of Hachimoji Nucleobases. Canonical Purine and Noncanonical Pyrimidine Forms Generated in the Gas Phase and Characterized by UV–Vis Photodissociation Action Spectroscopy

Abstract

Oxidation of nontraditional nucleobases 1-methylcytosine (hachimoji base S) and isoguanine (hachimoji base B) in gas-phase ternary complexes with Cu II (terpyridine) 2+ formed cation radicals that were characterized by tandem mass spectrometry, UV−vis photodissociation action spectroscopy in the 210−700 nm region, and ab initio calculations up to the CCSD(T)/complete basis set level of theory. Oxidation of S was accompanied by exothermic isomerization in the 1-methylcytosine ion (1 +• ), forming 1-methylene-2-hydroxy-4-aminopyrimidine cation radical (9 +• ) as a noncanonical distonic isomer of the nucleobase. Ion 9 +• was characterized by deuterium exchange experiments and provided a matching UV−vis action spectrum with the vibronic absorption spectrum from time-dependent density functional theory calculations. Oxidation of B resulted in the formation of a canonical isoguanine cation radical (12 +• ) as judged from the match of the experimental action spectrum with the calculated vibronic absorption spectrum. The calculated adiabatic ionization energies of canonical S and B, 8.51 and 7.76 eV, respectively, indicated exothermic electron transfer from B to S +• to proceed in an ionized base pair. Contrasting this, the lowest energy tautomer of ionized S (9 +• ) had a low adiabatic recombination energy, RE adiab = 5.70 eV, that would prevent it from oxidizing other nucleobases. Recombination energies of several nucleobase tautomers are reported and discussed.

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 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 .…”

The Elusive Noncanonical Isomers of Ionized 9-Methyladenine and 2′-Deoxyadenosine

“…67,68 Distonic Isomers of 2′-Deoxyadenosine Cation Radicals. The specific generation and stability of the elusive distonic isomer of 9-methyladenine cation radical, along with those of thymine 14 and methylcytosine, 15 indicated that nontraditional structures may play a role in DNA oxidation. To investigate this unusual aspect of nucleobase cation radical chemistry, we investigated the structures and relative energies of 2′deoxyadenosine isomers produced by H atom migrations in the canonical structure Ad1 +• .…”

“…The M06-2X TD-DFT calculations with the 6-31+G(d,p) and 6-311++G(2d,p) basis sets gave very similar results in terms of excitation energies and oscillator strength, as reported recently for other nucleobase cation radicals. 15,33 Therefore, the M06-2X/6-31+G(d,p) TD-DFT calculations were used to calculate all vibronic spectra at 310 K. The B3LYP/6-31+G(d,p) normal modes were used to generate Wigner distributions 53,54 of vibrational configurations of the ground electronic state. This was performed with the Newton-X 16 program.…”

“…Ionization by high-energy particles or photons disrupts the nucleobase π-electronic system, rendering nucleobase cation radicals susceptible to fast electron- and proton-transfer reactions within DNA or with surrounding molecules. Previous experimental and theoretical investigations of nucleobase cation radicals have largely treated these reactive species within the paradigm of canonical structures produced by electron removal from neutral nucleobases. − However, this paradigm has been challenged recently by the generation of stable noncanonical isomers of the thymine and 1-methylcytosine cation radicals in the gas phase. Computational energy analysis of the noncanonical cation radicals of both thymine (4-hydroxy-5-methylene-(1,3 H )­pyrimid-2-one) , and 1-methylcytosine (1-methylene-2-hydroxy-4-aminopyrimidine) revealed that they were substantially more stable than the pertinent canonical forms of oxidized DNA nucleobases.…”

“…Previous experimental and theoretical investigations of nucleobase cation radicals have largely treated these reactive species within the paradigm of canonical structures produced by electron removal from neutral nucleobases. − However, this paradigm has been challenged recently by the generation of stable noncanonical isomers of the thymine and 1-methylcytosine cation radicals in the gas phase. Computational energy analysis of the noncanonical cation radicals of both thymine (4-hydroxy-5-methylene-(1,3 H )­pyrimid-2-one) , and 1-methylcytosine (1-methylene-2-hydroxy-4-aminopyrimidine) revealed that they were substantially more stable than the pertinent canonical forms of oxidized DNA nucleobases. The discovery of noncanonical nucleobase cation radicals has been made possible by a combination of methods of gas-phase ion chemistry to generate such unusual species , and UV–vis photodissociation (UVPD) action spectroscopy − to characterize the ions and distinguish them from their canonical isomers and other protomers.…”