Influence of Sodium Cationization versus Protonation on the Gas-Phase Conformations and Glycosidic Bond Stabilities of 2′-Deoxyadenosine and Adenosine

Abstract

The influence of noncovalent interactions with a sodium cation on the gas-phase structures and N-glycosidic bond stabilities of 2'-deoxyadenosine (dAdo) and adenosine (Ado), [dAdo+Na](+) and [Ado+Na](+), are probed via infrared multiple photon dissociation (IRMPD) action spectroscopy and energy-resolved collision-induced dissociation (ER-CID) experiments. ER-CID experiments are also performed on the protonated forms of these nucleosides, [dAdo+H](+) and [Ado+H](+), for comparison purposes. Complementary electronic structure calculations are performed to determine the structures and relative stabilities of the stable low-energy conformations of the sodium cationized nucleoside complexes and to predict their IR spectra. Comparison between the measured IRMPD action spectra and calculated IR spectra enables the conformations of the sodium cationized nucleosides present in the experiments to be elucidated. The influence of sodium cationization versus protonation on the structures and IR spectra is elucidated by comparison to IRMPD and theoretical results previously reported for the protonated forms of these nucleosides. The influence of sodium cationization versus protonation on the glycosidic bond stability of the adenine nucleosides is determined by comparison of the ER-CID behavior of these systems. All structures present in the experiments are found to involve tridentate binding of Na(+) to the N3, O4', and O5' atoms forming favorable 5- and 6-membered chelation rings, which requires that adenine rotate to a syn configuration. This mode of sodium cation binding results in moderate flexibility of the sugar moiety such that the sugar puckering of the conformations present varies between C2'-endo and O4'-endo. Sodium cationization is found to be less effective toward activating the N-glycosidic bond than protonation for both dAdo and Ado. Both the IRMPD yields and ER-CID behavior indicate that the 2'-hydroxyl substituent of Ado stabilizes the N-glycosidic bond relative to that of dAdo.

Undervalued N3 Coordination Revealed in the Cisplatin Complex with 2′-Deoxyadenosine-5′-monophosphate by a Combined IRMPD and Theoretical Study

“…Finally, both N1 and N3 forms nicely reproduce the very strong signal detected above 1600 wavenumbers and dominantly associated with the NH 2 scissoring mode and the stretching of the C6=N bond, as mentioned previously (vide supra). Interestingly, although it is commonly held that the N3 site of adenine is not favored for electrophilic attack on adenine 11 , there is ample recent evidence made by IRMPD action spectroscopy showing that the N3 position is in fact favored in the protonation and alkali metal cation attachment of both the free base and adenine 9 DNA and RNA nucleosides [59][60][61] and nucleotides. 39 Also UVPD 62 and IRMPD 63 spectroscopy of alkali metal cation-adenine complexes and their hydrated forms confirm that N3 binding is preferred in a bidentate fashion with the N9 position on the tautomer A7 and support the view that N3 attack has likely been unduly undervalued.…”

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.…”

“…(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.…”

“…For example, modifications such as alkylation or protonation of DNA residues have previously been observed to weaken the glycosidic bond and accelerate the process of depurination [41–44]. Thus, hydrolytic instability of purine glycosidic bonds may impact nucleoside integrity, particularly under varying pH and ionic strength conditions and modification states [42, 45–47]. Stability of the glycosidic bond may also be influenced differentially by platination at varying sites on the nucleobase.…”

“…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].…”