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.
Infrared multiple photon dissociation (IRMPD) action spectroscopy experiments combined with theoretical calculations are performed to investigate the stable gas-phase conformations of the protonated adenine mononucleotides, [pdAdo+H](+) and [pAdo+H](+). Conformations that are present in the experiments are elucidated via comparative analyses of the experimental IRMPD spectra and the B3LYP/6-311+G(d,p) IR spectra predicted for the conformers optimized at this level of theory. N3 protonation is preferred as it induces base rotation, which allows a strong hydrogen bond to be formed between the excess proton of adenine and the phosphate moiety. In contrast, both N1 and N7 protonation are predicted to be >35 kJ/mol less favorable than N3 protonation. Only N3 protonated conformers are present in the experiments in measurable abundance. Both the low-energy conformers computed and the experimental IRMPD spectra of [pdAdo+H](+) and [pAdo+H](+) indicate that the 2'-hydroxyl moiety does not significantly impact the structure of the most stable conformer or the IRMPD spectral profile of [pAdo+H](+) vs that of [pdAdo+H](+). However, the 2'-hydroxyl leads to a 3-fold enhancement in the IRMPD yield of [pAdo+H](+) in the fingerprint region. Comparison of present results to those reported in a previous IRMPD study of the analogous protonated adenine nucleosides allows the effects of the phosphate moiety on the gas-phase conformations to be elucidated.
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.
Ionic liquids (ILs) have become increasingly popular due to their useful and unique properties, yet there are still many unanswered questions regarding their fundamental interactions. In particular, details regarding the nature and strength of the intrinsic cation–anion interactions and how they influence the macroscopic properties of ILs are still largely unknown. Elucidating the molecular-level details of these interactions is essential to the development of better models for describing ILs and enabling the purposeful design of ILs with properties tailored for specific applications. Current uses of ILs are widespread and diverse and include applications for energy storage, electrochemistry, designer/green solvents, separations, and space propulsion. To advance the understanding of the energetics, conformations, and dynamics of gas-phase IL clustering relevant to space propulsion, threshold collision-induced dissociation approaches are used to measure the bond dissociation energies (BDEs) of the 2:1 clusters of 1-alkyl-3-methylimidazolium cations and tetrafluoroborate, [2C n mim:BF4]+. The cation, [C n mim]+, is varied across the series, 1-ethyl-3-methylimidazolium [C2mim]+, 1-butyl-3-methylimidazolium [C4mim]+, 1-hexyl-3-methylimidazolium [C6mim]+, and 1-octyl-3-methylimidazolium [C8mim]+, to examine the structural and energetic effects of the size of the 1-alkyl substituent on binding. Complementary electronic structure calculations are performed to determine the structures and energetics of the [C n mim]+ and [BF4]− ions and their binding preferences in the (C n mim:BF4) ion pairs and [2C n mim:BF4]+ clusters. Several levels of theory, B3LYP, B3LYP-GD3BJ, and M06-2X, using the 6-311+G(d,p) basis set for geometry optimizations and frequency analyses and the 6-311+G(2d,2p) basis set for energetics, are benchmarked to examine their abilities to properly describe the nature of the binding interactions and to reproduce the measured BDEs. The modest structural variation among these [C n mim]+ cations produces only minor structural changes and variation in the measured BDEs of the [2C n mim:BF4]+ clusters. Present findings indicate that the dominant cation–anion interactions involve the 3-methylimidazolium moieties and that these clusters are sufficiently small that differences in packing effects associated with the variable length of the 1-alkyl substituents are not yet significant.
To gain a better understanding of the binding mechanism and assist in the optimization of chemical probing and drug design applications, experimental and theoretical studies of a series of amino acid-linked cisplatin derivatives are being pursued. Glyplatin (glycine-linked cisplatin) was chosen for its structural simplicity and to enable backbone effects to be separated from side-chain effects on the structure and reactivity of ornithine- and lysine-linked cisplatin (Ornplatin and Lysplatin, respectively). Infrared multiple photon dissociation (IRMPD) action spectroscopy experiments were performed on Glyplatin to characterize its structure and guide the selection of the most effective hybrid theoretical approach for determining its structure and IR spectrum. The simplicity of the Glyplatin system allows a wide variety of density functionals, treatments of the Pt center including the use of all-electron basis sets vs valence basis sets combined with an effective core potential (ECP), and basis sets for all other atoms to be evaluated at a reasonable computational cost. The results for Glyplatin provide the foundation for calculations of more complex amino acid-linked cisplatin derivatives such as Ornplatin and Lysplatin. Present results suggest that the B3LYP/mDZP/def2-TZVP hybrid method can be effectively employed for structural and IR characterization of more complex amino acid-linked cisplatin complexes and their nucleic acid derivatives.
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