Influence of 2′-fluoro modification on glycosidic bond stabilities and gas-phase ion structures of protonated pyrimidine nucleosides

Devereaux, Zachary J.; Roy, H. A.; He, Chenchen; Zhu, Yunlong; Cunningham, N. A.; Hamlow, L. A.; Berden, Giel; Rodgers, M. T.

doi:10.1016/j.jfluchem.2018.12.004

Cited by 13 publications

(15 citation statements)

References 66 publications

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“…Two sequential dissociation pathways, both of which involve glycosidic bond cleavage occur in competition. In all cases, the excess proton is preferentially retained by the departing base, reaction , whereas retention of the excess proton by the sugar moiety is much less favorable (by more than an order of magnitude), reaction . The fragmentation patterns observed for the ( x Cyd)H + ( x Cyd) base pairs parallel those observed in previous studies of protonated base pairs of cytosine nucleobase and cytidine nucleoside analogues as well as that of iosloated protonated cytidine nucleoside analogues using TCID − , and IRMPD − techniques.…”

Section: Resultssupporting

confidence: 74%

Influence of 5-Methylation and the 2′- and 3′-Hydroxy Substituents on the Base Pairing Energies of Protonated Cytidine Nucleoside Analogue Base Pairs: Implications for the Stabilities ofi-Motif Structures

2021

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Repetitive nucleic acid sequences, which occur in abundance throughout the mammalian genome, are of enormous research interest due to their potential to adopt fascinating and unusual molecular structures such as the i-motif. In remarkable contrast to the DNA double helix, i-motif conformations are stabilized by protonated cytosine base pairs, (Cyt)H + (Cyt), that are centrally located in the core of the i-motif and intercalated vertically in an antiparallel fashion. An in-depth understanding of how modifications influence the stability of i-motif conformations is a prerequisite to understanding their biological functions and the development of effective means of tuning their stability for specific medical and technological applications. Here, the influence of the 2′-and 3′-hydroxy substituents of the sugar moieties and 5-methylation of the cytosine nucleobases on the base-pairing interactions of protonated cytidine nucleoside analogue base pairs, (xCyd)H + (xCyd), are examined by complementary threshold collision-induced dissociation techniques and computational methods. The xCyd nucleosides examined include the canonical DNA and RNA cytidine nucleosides, 2′-deoxycytidine (dCyd) and cytidine (Cyd), as well as several modified cytidine nucleoside analogues, 2′,3′-dideoxycytidine (ddCyd), 5-methyl-2′-deoxycytidine (m 5 dCyd), and 5-methylcytidine (m 5 Cyd). Comparisons among these model base pairs indicate that the 2′-and 3′-hydroxy substituents of the sugar moieties have very little influence on the strength of the base-pairing interactions, whereas 5-methylation of the cytosine nucleobases is found to enhance the strength of the base-pairing interactions. The increase in stability resulting from 5-methylation is only modest but is more than twice as large for the DNA than RNA protonated cytidine base pair. Overall, present results suggest that canonical DNA i-motif conformations should be more stable than analogous RNA i-motif conformations and that 5-methylation of cytosine residues, a significant epigenetic marker, provides greater stabilization to DNA than RNA i-motif conformations.

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Section: Resultssupporting

confidence: 74%

Influence of 5-Methylation and the 2′- and 3′-Hydroxy Substituents on the Base Pairing Energies of Protonated Cytidine Nucleoside Analogue Base Pairs: Implications for the Stabilities ofi-Motif Structures

2021

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“…In theory, the electron-withdrawing fluoro substituent should lower the p K a of the 2′-proton, enhancing reactivity. However, the substitution of the 2′-position from a hydrogen to a fluorine enhances the stability of the N -glycosidic bond, and this effect seems to dominate. Similarly, the N -glycosidic bond is also stronger in a ribonucleoside than a deoxynucleoside.…”

Section: Results and Discussionmentioning

confidence: 99%

Organocatalytic Conversion of Nucleosides to Furanoid Glycals

Mao

Chung

et al. 2021

J. Org. Chem.

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A class of organocatalysts that are highly active for the conversion of 2′-deoxynucleosides to furanoid glycals have been discovered. These phosphorimides, (Ph 2 PS) 2 NH and (Ph 2 PSe) 2 NH, were shown to effectively mediate persilylation of 2′-deoxynucleosides allowing the elimination of the nucleobase giving the corresponding glycal. These mild conditions were demonstrated in the syntheses of glycals with various substitution patterns while minimizing the formation of undesired byproducts and expanding the scope of this methodology.

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“…These plots contain the energetic information on the dissociation pathway(s) but need a specific treatment to extract quantitative data. In general, the ERMS sigmoid curves (generated by any MS technique) are modeled by a logistic function, − involving four or five parameters (depending on the symmetry of the sigmoid curve), as described in the Supporting Information.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…In studies conducted with QIT instruments, for which the absolute collision energy cannot be established directly, a specific point of the sigmoid curve must be selected as a quantitative parameter related to the BDE. Essentially, two specific points of the sigmoid were used in ERMS studies using QIT: (i) the NCE value (or RF voltage) at which the relative intensity of the precursor ion is reduced by 50 %, [35][36][37][38][39][40]41 called here NCE50, and (ii) the so-called "Appearance Energy" (AE). 33,42 For the ERMS experiments reported here, the ions corresponding to the two-coordinate cationic gold(I) complexes L(Au + )S are isolated in the gas phase and collided with the helium damping-gas of the ion trap.…”

Section: Experimental Binding Energetics Of Organic Substrates To L(au + ) Ions By Ermsmentioning

confidence: 99%

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Energetics and Structures of Adducts of JohnPhos(Au⁺), PPh₃(Au⁺), and IPr(Au⁺) with Organic Substrates: A Mass Spectrometry and DFT Study

et al. 2021

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We report a mass spectrometry study of the interaction between three representative Au(I) catalysts containing the ligands L = JohnPhos (2-biphenylyl[bis(2-methyl-2-propanyl)]phosphine), TPP (PPh3, triphenylphosphine), the N-heterocyclic carbene IPr (carbene form of 1,3-bis(2,6-diisopropylphenyl)-2,3-dihydro-1H-imidazole), and 27 organic molecules S (substrates) bearing organic functionalities often present in reactants (alkenes, alkynes, allenes, enol ethers, aldehydes, ketones, epoxides). An experimental scale of gas-phase relative binding energy between three L(Au + ) ions and the organic substrates was established by energy-resolved experiments of the 81 cationic two-coordinate gold adducts L(Au + )S using a quadrupole ion trap mass spectrometer. The experimental scale is expressed in units of normalized collision energy for 50% dissociation (NCE50) of the precursor ion. In parallel, the gas-phase bond dissociation energetics and the structure of adducts were probed by DFT calculations. The experimental affinity order of each substrate for the three cationic gold complexes L(Au + ), IPr(Au + ) > TPP(Au + ) > JohnPhos(Au + ), is well reproduced by the calculated bond dissociation energies ΔE. At the computational level used in this study, the agreement between the calculated ΔE and the experimental NCE50 values is limited to series of substrates with the same functionality, and reasonable correlations NCE50 vs. ΔE are observed within series. The DFT-optimized structures are discussed and compared with available X-ray crystal structures. Although no general trend can be observed between bond lengths, or their changes upon coordination with the L(Au + ) cations, and dissociation energies, a significant correlation between Au-O distance (S = O-bases) and ΔE is observed.

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Influence of 2′-fluoro modification on glycosidic bond stabilities and gas-phase ion structures of protonated pyrimidine nucleosides

Cited by 13 publications

References 66 publications

Influence of 5-Methylation and the 2′- and 3′-Hydroxy Substituents on the Base Pairing Energies of Protonated Cytidine Nucleoside Analogue Base Pairs: Implications for the Stabilities ofi-Motif Structures

Influence of 5-Methylation and the 2′- and 3′-Hydroxy Substituents on the Base Pairing Energies of Protonated Cytidine Nucleoside Analogue Base Pairs: Implications for the Stabilities ofi-Motif Structures

Organocatalytic Conversion of Nucleosides to Furanoid Glycals

Energetics and Structures of Adducts of JohnPhos(Au⁺), PPh₃(Au⁺), and IPr(Au⁺) with Organic Substrates: A Mass Spectrometry and DFT Study

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Influence of 2′-fluoro modification on glycosidic bond stabilities and gas-phase ion structures of protonated pyrimidine nucleosides

Cited by 13 publications

References 66 publications

Influence of 5-Methylation and the 2′- and 3′-Hydroxy Substituents on the Base Pairing Energies of Protonated Cytidine Nucleoside Analogue Base Pairs: Implications for the Stabilities ofi-Motif Structures

Influence of 5-Methylation and the 2′- and 3′-Hydroxy Substituents on the Base Pairing Energies of Protonated Cytidine Nucleoside Analogue Base Pairs: Implications for the Stabilities ofi-Motif Structures

Organocatalytic Conversion of Nucleosides to Furanoid Glycals

Energetics and Structures of Adducts of JohnPhos(Au+), PPh3(Au+), and IPr(Au+) with Organic Substrates: A Mass Spectrometry and DFT Study

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Energetics and Structures of Adducts of JohnPhos(Au⁺), PPh₃(Au⁺), and IPr(Au⁺) with Organic Substrates: A Mass Spectrometry and DFT Study