Theoretical Study of the Protonation of the One-Electron-Reduced Guanine–Cytosine Base Pair by Water

Abstract

Prototropic equilibria in ionized DNA play an important role in charge transport and radiation damage of DNA and, therefore, continue to attract considerable attention. Although it is well-established that electron attachment will induce an interbase proton transfer from N1 of guanine (G) to N3 of cytosine (C), the question of whether the surrounding water in the major and minor grooves can protonate the one-electron-reduced G:C base pair still remains open. In this work, density functional theory (DFT) calculations were employed to investigate the energetics and mechanism for the protonation of the one-electron-reduced G:C base pair by water. Through the calculations of thermochemical cycles, the protonation free energies were estimated to be in the range of 11.6-14.2 kcal/mol. The calculations for the models of C(•-)(H(2)O)(8) and G(-H1)(-)(H(2)O)(16), which were used to simulate the detailed processes of protonation by water before and after the interbase proton transfer, respectively, revealed that the protonation proceeds through a concerted double proton transfer involving the water molecules in the first and second hydration shells. Comparing the present results with the rates of interbase proton transfer and charge transfer along DNA suggests that protonation on the C(•-) moiety is not competitive with interbase proton transfer, but the possibility of protonation on the G(-H1)(-) moiety after interbase proton transfer cannot be excluded. Electronic-excited-state calculations were also carried out by the time-dependent DFT approach. This information is valuable for experimental identification in the future.

Effects of Positive and Negative Ionization on Prototropy in Pyrimidine Bases: An Unusual Case of Isocytosine

“…Prototropy in heterocompounds was already well-known, when Watson and Crick reported the DNA structure . Taking intramolecular proton-transfer equilibria in nucleobases into account, they proposed an interesting mechanism of point mutations, developed later by other chemists. − In normal DNA, pyrimidine and purine nucleobases take their canonical forms {Figure S1 in Supporting Information (SI)} and interact specifically by formation of H-bonds, i.e., cytosine ( C ) is paired with guanine ( G ), and thymine ( T ) is paired with adenine ( A ). However, in some conditions the canonical forms ( C , G , T , or A ) can be transformed into their rare forms ( C *, G *, T *, or A *), and the natural pairing can be disordered.…”

Biomimetic Intrafibrillar Mineralization of Type I Collagen with Intermediate Precursors-loaded Mesoporous Carriers

“…In comparison, the concentration of Ca, P and Si in Pa-ACP loaded MSNs was 0.06, <0.05 and 43.27 wt% respectively. Based on these information, it is speculated that physisorption of Pa-ACP may be attributed to a combination of capillary action of the mesopores 33 , as indicated by the presence of Ca and P in Pa-ACP loaded, non-amine-functionalized MSNs, as well as electrostatic attraction between the oppositely-charged Pa-ACPs and amine functionalities in the MSNs 34 . Because the amount of Ca and P present in the loaded MSNs were far less than the amount present in AF-MSNs, we speculate that physisorption via electrostatic attraction plays a more important role in the loading of the Pa-ACPs than capillary action via surface wetting of the Pa-ACP with the surface of the mesoporous silica.…”

Charge transfer dynamics in DNA revealed by time-resolved spectroscopy

“…From the global analysis, the proton transfer rate was estimated to be 2.6 × 10 10 s –1 , which agreed with the theoretical estimation. 76 In addition, generation of DPA was not confirmed with C3 and C4, indicating that multiple C's completely terminated the EET in DNA.…”