The acidity of uracil and uracil analogs in the gas phase: Four surprisingly acidic sites and biological implications

Abstract

The gas phase acidities of a series of uracil derivatives (1-methyluracil, 3-methyluracil, 6-methyluracil, 5,6-dimethyluracil, and 1,3-dimethyluracil) have been bracketed to provide an understanding of the intrinsic reactivity of uracil. The experiments indicate that in the gas phase, uracil has four sites more acidic than water. Among the uracil analogs, the N1-H sites have ⌬H acid values of 331-333 kcal mol Ϫ1 ; the acidity of the N3 sites fall between 347-352 kcal mol Ϫ1 . The vinylic C6 in 1-methyluracil and 3-methyluracil brackets to 363 kcal mol Ϫ1 , and 369 kcal mol Ϫ1 in 1,3-dimethyluracil; the C5 of 1,3-dimethyluracil brackets to 384 kcal mol Ϫ1 . Calculations conducted at B3LYP/6-31ϩG* are in agreement with the experimental values. The bracketing of several of these sites involved utilization of an FTMS protocol to measure the less acidic site in a molecule that has more than one acidic site, establishing the generality of this method. In molecules with multiple acidic sites, only the two most acidic sites were bracketable, which is attributable to a kinetic effect. The measured acidities are in direct contrast to in solution, where the two most acidic sites of uracil (N1 and N3) are indifferentiable. The vinylic C6 site is also particularly acidic, compared to acrolein and pyridine. The biological implications of these results, particularly with respect to enzymes for which uracil is a substrate, are discussed. (J Am Soc Mass Spectrom 2002, 13, 985-995)

Unimolecular Reactivity of Uracil–Cu2+ Complexes in the Gas Phase

“…For this reason much effort has been devoted to investigating the reactivity of this compound and its acidity, [1][2][3][4][5][6] basicity, [2,7] hydrogen-bonding ability towards other DNA species, [2] and solvation by water molecules. [2,4,5,8] Interaction with metal ions is also an important part of this research activity, [9][10][11][12][13] due to its ubiquitous presence in biological media, where it participates in different processes, such as enzyme regulation and stabilization of nucleic acids.…”

An Experimental and Theoretical Investigation of Gas‐Phase Reactions of Ca2+with Glycine

“…Interestingly, the stability of anionic uracil in the active site of uracil-DNA glycosylase, established by means of contemporary NMR techniques, [2] is consistent with the enhanced intrinsic acidity of the N1 site, and contrary to the expectation based on solution acidities. [3] Similarly, gas-phase studies of the interaction of metal cations with amino acids can provide useful insights into the corresponding interactions with more complex biologically relevant systems such as peptides or proteins. In this respect, glycine represents the simplest model for such a theoretical and experimental investigation.…”

N-[2-(9H-Carbazol-9-yl)ethyl]-4-(methylsulfonyl)aniline

“…1). The 2,4-dioxopyrimidin-1-ide anion is generated by deprotonation of the N4 atom at the 1 position of the pyrimidine-dione ring (Kurinovich & Lee 2002;Jang et al, 2001;Nguyen et al, 1998). The sixmembered piperazine ring (N1/C8/C9/N2/C10/C11) in the cation fragement adopts a slightly distorted chair conformation with puckering parameters: Q = 0.5774 (17) Å, θ = 177.86 (17) °, and φ = 129 (4) ° and contains a positively charged N atom (N2) with quaternary character.…”