Effects of sodium cationization versus protonation on the conformations and N-glycosidic bond stabilities of sodium cationized Urd and dUrd: solution conformation of [Urd+Na]⁺is preserved upon ESI

Abstract

Uridine (Urd) is one of the naturally occurring pyrimidine nucleosides of RNA. 2'-Deoxyuridine (dUrd) is a naturally occurring modified form of Urd, but is not one of the canonical DNA nucleosides. In order to understand the effects of sodium cationization on the conformations and energetics of Urd and dUrd, infrared multiple photon dissociation (IRMPD) action spectroscopy experiments and density functional theory (DFT) calculations are performed. By comparing the calculated IR spectra of [Urd+Na] and [dUrd+Na] with the measured IRMPD spectra, the stable low-energy conformers populated in the experiments are determined. Anti oriented bidentate O2 and O2' binding conformers of [Urd+Na] are the dominant conformers populated in the experiments, whereas syn oriented tridentate O2, O4', and O5' binding conformers of [dUrd+Na] are dominantly populated in the experiments. The 2'-hydroxyl substituent of Urd stabilizes the anti oriented O2 binding conformers of [Urd+Na]. Significant differences between the measured IRMPD and calculated IR spectra for complexes of [Urd+Na] and [dUrd+Na] involving minor tautomeric forms of the nucleobase make it obvious that none are populated in the experiments. Survival yield analyses based on energy-resolved collision-induced dissociation (ER-CID) experiments suggest that the relative stabilities of protonated and sodium cationized Urd and dUrd follow the order: [dUrd+H] < [Urd+H] < [dUrd+Na] < [Urd+Na]. The 2'-deoxy modification is found to weaken the glycosidic bond of dUrd versus that of Urd for the sodium cationized uridine nucleosides.

Amino acid-linked platinum(II) compounds: non-canonical nucleoside preferences and influence on glycosidic bond stabilities

“…(1) [57]in which and are the ion intensities of the fragment and precursor ions, respectively; x represents fragments in which the glycosidic bond remains intact. Data analyses were performed using SigmaPlot 10.0 (Systat Software, Inc., San Jose, CA, USA) and custom software developed in the Rodgers laboratory and reported previously [42, 48–51]. The GBC survival yield was plotted as a function of the rf excitation amplitude.…”

“…Stability of the glycosidic bond may also be influenced differentially by platination at varying sites on the nucleobase. In this study, we investigated the impact of AlaPt and OrnPt adducts on relative glycosidic bond strengths by employing energy-resolved collision-induced dissociation (ER-CID) tandem mass spectrometry and survival yield analysis [42, 48–51]. In a previous theoretical study, evaluation of the effects of cisPt modification indicated that platination at N7 does not destabilize the dGuo glycosidic bond [52].…”

Relative glycosidic bond stabilities of naturally occurring methylguanosines: 7-methylation is intrinsically activating

“…N-glycosidic bond cleavage with retention of the cation by the nucleobase, the sole fragmentation channel observed in the reactions performed here, is often the intrinsically lowest energy unimolecular dissociation pathway observed in the CID of nucleosides (see the Supplementary Material for a more in-depth overview of the canonical nucleoside CID reaction products). [52][53][54][55][56][60][61][62][63][64] In previous work by Wu et al, 61 the fragmentation pathways observed for gas phase [GuoþH] þ and [dGuoþH] þ were mechanistically mapped to proceed through a stepwise E1 elimination reaction by electronic structure calculations and comparisons with guided ion beam mass spectrometry (GIBMS) TCID activation energy thresholds. These results suggest the solvent-free substitution reaction pathway to proceed first by the rate-limiting elongation/cleavage of the C1 0 -N9 glycosidic bond, forming an oxocarbenium ion-like transition state on the sugar and an interaction of the N9 heteroatom electron density with the C2 0 H hydrogen, followed by transfer of that C2 0 proton to the N9 atom of the nucleobase with the formation of a C1 0 ¼C2 0 p-bond and an unsaturated planar sugar moiety.…”

“…Overall, the QIT MS ER-CID and GIBMS TCID reports on the canonical nucleosides consistently display two major trends: one, the RNA nucleoside glycosidic bonds are more stable than their DNA counterparts, and two, protonation activates the glycosidic bonds more effectively than sodium cationization. [52][53][54][55][56][60][61][62][63] For example, the RNA guanosine form, Guo, requires more energy to cleave its glycosidic bond than the DNA form, dGuo. 52,61 The TCID studies of [GuoþH] þ and [dGuoþH] þ yielded bond activation energies of 114.8 AE 2.9 and 93.6 AE 2.9 kJ/mol, respectively.…”

“…Tandem mass spectrometry (MS/MS) approaches have proven effective in providing insight into the intrinsic properties of nucleic acid constituents. Performing collision-induced dissociation (CID) in an energy-resolved fashion has also proved useful for a variety of purposes including the separation of isobaric compounds, 50 nucleic acid constituent proton affinity (PA) measurements, 51 relative stability measurements of canonical nucleosides, [52][53][54][55][56] glycosyl phosphates, 57 9-ethylguanine tetrads, 58 nucleic acid-drug complexes, 59 and accurate absolute glycosidic bond cleavage thermochemistry measurements via threshold collision-induced dissociation (TCID). [60][61][62][63] Here we use energy-resolved collisioninduced dissociation (ER-CID) MS/MS experiments performed in a quadrupole ion trap mass spectrometer (QIT MS) to elucidate the relative intrinsic N-glycosidic bond stabilities of the protonated and sodium cationized forms of canonical Guo and five methylguanosines (Guom, m 1 Guo, m 7 Guo, m 2 2 Guo, and m 2 2 Guom).…”