Cisplatin, (NH3)2PtCl2, has been known as a successful metal-based anticancer drug for more than half a century. Its analogue, Argplatin, arginine-linked cisplatin, (Arg)PtCl2, is being investigated because it exhibits reactivity...
Modifications to a Paul-type quadrupole ion trap mass spectrometer providing optical access to the trapped ion cloud as well as hardware and software for coupling to a table-top IR optical parametric oscillator laser (OPO) are detailed. Critical experimental parameters for infrared multiple photon dissociation (IRMPD) on this instrument are characterized. IRMPD action spectra, collected in the hydrogen-stretching region with this instrument, complemented by spectra in the IR fingerprint region acquired at the FELIX facility, are employed to characterize the structures of the protonated forms of 2-thiouridine, [sUrd+H], and 4-thiouridine, [sUrd+H]. The measured spectra are compared with predicted linear IR spectra calculated at the B3LYP/6-311+G(d,p) level of theory to determine the conformers populated in the experiments. This comparison indicates that thiation at the 2- or 4-positions shifts the protonation preference between the 2,4-H tautomer and 4-protonation in opposite directions versus canonical uridine, which displays a roughly equal preference for the 2,4-H tautomer and O4 protonation. As found for canonical uridine, protonation leads to a mixture of conformers exhibiting C2'-endo and C3'-endo sugar puckering with an anti nucleobase orientation being populated for both 2- and 4-thiated uridine. Graphical Abstract ᅟ.
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.
Thymidine (dThd) is a fundamental building block of DNA nucleic acids, whereas 5-methyluridine (Thd) is a common modified nucleoside found in tRNA. In order to determine the conformations of the sodium cationized thymine nucleosides [dThd+Na] and [Thd+Na] produced by electrospray ionization, their infrared multiple photon dissociation (IRMPD) action spectra are measured. Complementary electronic structure calculations are performed to determine the stable low-energy conformations of these complexes. Geometry optimizations and frequency analyses are performed at the B3LYP/6-311+G(d,p) level of theory, whereas energies are calculated at the B3LYP/6-311+G(2d,2p) level of theory. As protonation preferentially stabilizes minor tautomers of dThd and Thd, tautomerization facilitated by Na binding is also considered. Comparisons of the measured IRMPD and computed IR spectra find that [dThd+Na] prefers tridentate (O2,O4',O5') coordination to the canonical 2,4-diketo form of dThd with thymine in a syn orientation. In contrast, [Thd+Na] prefers bidentate (O2,O2') coordination to the canonical 2,4-diketo tautomer of Thd with thymine in an anti orientation. Although 2,4-dihydroxy tautomers and O2 protonated thymine nucleosides coexist in the gas phase, no evidence for minor tautomers is observed for the sodium cationized species. Consistent with experimental observations, the computational results confirm that the sodium cationized thymine nucleosides exhibit a strong preference for the canonical form of the thymine nucleobase. Survival yield analyses based on energy-resolved collision-induced dissociation (ER-CID) experiments suggest that the relative stabilities of protonated and sodium cationized dThd and Thd follow the order [dThd+H] < [Thd+H] < [dThd+Na] < [Thd+Na]. Graphical Abstract ᅟ.
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