Gas-Phase Conformations and N-Glycosidic Bond Stabilities of Sodium Cationized 2′-Deoxyguanosine and Guanosine: Sodium Cations Preferentially Bind to the Guanine Residue

Abstract

2'-Deoxyguanosine (dGuo) and guanosine (Guo) are fundamental building blocks of DNA and RNA nucleic acids. In order to understand the effects of sodium cationization on the gas-phase conformations and stabilities of dGuo and Guo, infrared multiple photon dissociation (IRMPD) action spectroscopy experiments and complementary electronic structure calculations are performed. The measured IRMPD spectra of [dGuo+Na] and [Guo+Na] are compared to calculated IR spectra predicted for the stable low-energy structures computed for these species to determine the most favorable sodium cation binding sites, identify the structures populated in the experiments, and elucidate the influence of the 2'-hydroxyl substituent on the structures and IRMPD spectral features. These results are compared with those from a previous IRMPD study of the protonated guanine nucleosides to elucidate the differences between sodium cationization and protonation on structure. Energy-resolved collision-induced dissociation (ER-CID) experiments and survival yield analyses of protonated and sodium cationized dGuo and Guo are performed to compare the effects of these cations toward activating the N-glycosidic bonds of these nucleosides. For both [dGuo+Na] and [Guo+Na], the gas-phase structures populated in the experiments are found to involve bidentate binding of the sodium cation to the O6 and N7 atoms of guanine, forming a 5-membered chelation ring, with guanine found in both anti and syn orientations and C2'-endo (T or T) puckering of the sugar. The ER-CID results, IRMPD yields and the computed C1'-N9 bond lengths indicate that sodium cationization activates the N-glycosidic bond less effectively than protonation for both dGuo and Guo. The 2'-hydroxyl substituent of Guo is found to impact the preferred structures very little except that it enables a 2'OH···3'OH hydrogen bond to be formed, and stabilizes the N-glycosidic bond relative to that of dGuo in both the sodium cationized and protonated complexes.

Structural characterization of nucleotide 5′-triphosphates by infrared ion spectroscopy and theoretical studies

“…Previous IRMPD spectroscopy studies by Rodgers and coworkers have provided a large body of data on metal-complexed nucleobases and nucleosides. [41][42][43][44][45][46][47][48] IRMPD spectra of metal-complexed NTPs have thus far not been reported and are an important next step in the characterization of the intrinsic interactions of specific NTPs.…”

“…Collision-induced dissociation (CID) is performed to evaluate the fragmentation behaviour of the systems, while infrared multiple-photon dissociation (IRMPD) spectroscopy in combination with quantum-chemical calculations is used to map intramolecular hydrogen bond interactions and deprotonation sites. Related systems such as protonated and deprotonated mononucleotides, [35][36][37][38][39] mononucleotide clusters, 40 protonated and metal-complexed nucleobases [41][42][43][44][45][46][47][48] and phosphate-metal complexes 49,50 have recently been successfully characterized using these methodologies.…”

How nature covers its bases

“…Most of these approaches can also be implemented for cold ions in cryogenic traps, which is outside the scope of this perspective. [75][76][77][78][79] It is worth stressing that the isomer specificity afforded by double resonant techniques constitutes a great strength of gas phase spectroscopy.…”

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

“…ER-CID experiments of the HPLC fractions containing the AlaPt-Ado and OrnPt-Ado adducts were performed on a quadrupole ion trap mass spectrometer (QIT MS, amaZon ETD, Bruker Daltonics, Billerica, MA, USA). The method has been described in detail in previous work [42, 50, 51]. Briefly, HPLC fractions were vacuum dried and then redissolved in an MeOH:ddH 2 O (50:50 v/v) mixture.…”

“…The rf excitation amplitude required to produce 50% glycosidic bond cleavage (GBC 50% ) was extracted by fitting of the survival yield curve using the four-parameter logistic dynamic equation (Eq. 2) [42, 50, 51]:…”