Anionic derivatives of uracil: fragmentation and reactivity

Abstract

Uracil is an essential biomolecule for terrestrial life, yet its prebiotic formation mechanisms have proven elusive for decades. Meteorites have been shown to contain uracil and the interstellar abundance of aromatic species and nitrogen-containing molecules is well established, providing support for uracil's presence in the interstellar medium (ISM). The ion chemistry of uracil may provide clues to its prebiotic synthesis and role in the origin of life. The fragmentation of biomolecules provides valuable insights into their formation. Previous research focused primarily on the fragmentation and reactivity of cations derived from uracil. In this study, we explore deprotonated uracil-5-carboxylic acid and its anionic fragments to elucidate novel reagents of uracil formation and to characterize the reactivity of uracil's anionic derivatives. The structures of these fragments are identified through theoretical calculations, further fragmentation, experimental acidity bracketing, and reactivity with several detected and potential interstellar species (SO2, OCS, CS2, NO, N2O, CO, NH3, O2, and C2H4). Fragmentation is achieved through collision induced dissociation (CID) in a commercial ion trap mass spectrometer, and all reaction rate constants are measured using a modification of this instrument. Experimental data are supported by theoretical calculations at the B3LYP/6-311++G(d,p) level of theory. Lastly, the astrochemical implications of the observed fragmentation and reaction processes are discussed.

Microhydration of Deprotonated Nucleobases

“…According to the in vacuo ab initio calculations, the N1 – anion of [ U -H] – is more stable than N3 – by 58.5 kJ/mol [ 59 ]; for [5F U -H] – this difference is 49.9 kJ/mol [ 60 ]. The energy barrier (185.4 kJ/mol) calculated [ 61 ] for the uracil N1 – —> N3 – conversion is too high to be overcome at thermal energies in our instrument. Therefore, it is reasonable to assume that the N1 – would be the predominant form of the [NB-H] – anions of uracil and its derivatives (structure 1 in Scheme 2 ) formed by ESI in the present study and these species are the most favorable precursors for hydrated complexes.…”

Gas-Phase Reactions of Deprotonated Nucleobases with H, N, and O Atoms

“…Previous studies demonstrated that gas-phase biological ions formed by ESI generally retain their most stable solution structure. 32 The reactions of the nucleobase anions with H-atoms proceed exclusively by associative electron detachment, in which a bond is formed to hydrogen and the electron is detached. We have observed this mechanism for a wide variety of negative ions, and indeed, we have found only two extremely stable anions (C 2 N 3 − and C 4 N 3 − ) that are unreactive with Hatoms.…”

“…The thermochemical values, Δ r H theory, listed in Table , were determined with the computational program suite Gaussian 09 and the B3LYP/6-311++G­(d,p) level of theory with thermal corrections using the rigid rotor–harmonic oscillator approximation to provide Δ r H theory values at 298 K. For these calculations, the parent nucleobases were assumed to be deprotonated at the most thermodynamically favorable position, that is, N9 for adenine and guanine and N1 for cytosine, thymine, and uracil (Figure ). Previous studies demonstrated that gas-phase biological ions formed by ESI generally retain their most stable solution structure …”

A Spontaneous Ring‐Opening Reaction Leads to a Repair‐Resistant Thymine Oxidation Product in Genomic DNA

“…The uracil ring has long been known to be unstable and also to exert the least aromaticity of all the nucleic acid bases . However, most experimental and computational work has mainly focused on the behaviour of uracil under harsh fragmentation and ionising conditions in mass spectrometry or of astrochemical relevance . 5fU was noted to undergo ring opening, but through the cleavage at the N 1 −C 6 bond, while reacting with primary alkyl amines and enamines .…”

“…For anionic U − , a density functional theory investigation of enforced fragmentation revealed the relative strengths of N 3 −C 4 over N 1 −C 2 over C 5 −C 6 bonds with 1.622, 1.710 and 5.459 eV (1 eV=23.061 kcal mol −1 ) barriers for cleavage . Cole et al . reported a 20.8 kcal mol −1 energy barrier for N 1 −C 2 cleavage in N 3 ‐deprotonated U − .…”