Hydrogen-Bonded Proton Transfer in the Protonated Guanine-Cytosine (GC+H)⁺ Base Pair

Abstract

The single proton transfer at the different sites of the Watson-Crick (WC) guanine-cytosine (GC) DNA base pair are studied here using density functional methods. The conventional protonated structures, transition state (TS) and proton-transferred product (PT) structures of every relevant species are optimized. Each transition state and proton-transferred product structure has been compared with the corresponding conventional protonated structure to demonstrate the process of proton transfer and the change of geometrical structures. The relative energies of the protonated tautomers and the proton-transfer energy profiles in gas and solvent are analyzed. The proton-transferred product structure G(+H(+))-H(+)C(N3)(-H(+))(PT) has the lowest relative energy for which only two hydrogen bonds exist. Almost all 14 isomers of the protonated GC base pair involve hydrogen-bonded proton transfer following the three pathways, with the exception of structure G-H(+)C(O2). When the positive charge is primarily "located" on the guanine moiety (H(+)G-C, G-H(+)C(C4), and G-H(+)C(C6)), the H(1) proton transfers from the N(1) site of guanine to the N(3) site of cytosine. The structures G-H(+)C(C5) and G-H(+)C(C4) involve H(4a) proton transfer from the N(4) of cytosine to the O(6) site of guanine. H(2a) proton transfer from the N(2) site of guanine to the O(2) site of cytosine is found only for the structure G-H(+)C(C4). The structures to which a proton is added on the six-centered sites adjoining the hydrogen bonds are more prone to proton transfer in the gas phase, whereas a proton added on the minor groove and the sites adjoining the hydrogen bonds is favorable to the proton transfer in energy in the aqueous phase.

Molecular Switching Behavior in Isosteric DNA Base Pairs

“…Protonated DNA base pairs play a key role in the processes of DNA damage and DNA repair. Thus, systematic studies on the structure and energies of the protonated guanine–cytosine (G‐C) base pair have been previously performed 5. Experimentally, the structure and thermodynamic stability of different DNA duplexes are determined by a combination of physical methods including X‐ray crystallography, ultraviolet melting, and NMR spectroscopy 6.…”

A theoretical study of hemiacetal formation from the reaction of methanol with derivatives of CX3CHO (X = H, F, Cl, Br and I)

“…The numerous cases reported can be classified based on the occurring mechanism. For instance, direct proton transfer can be found in the protonated guanine–cytosine base pair of the Watson–Crick chain of DNA, assistance with donor molecules of hydrogen bonds, like water, in peptide systems or carbohydrate systems, in clusters, occurring in solid and crystalline systems or even in the excited state …”

Theoretical Comparison of the Stabilities of Hoogsteen and Watson–Crick Conformations for Proton‐bound Base‐pairing of Nucleic Acid Bases and Nucleosides in the Gas Phase

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Since the discovery of the Watson-Crick (WC) doublehelical structures of DNA molecules, 1 the specific binding involved in G-C (guanine-cytosine) and A-T (adeninethymine) base-pairing has been known to play a key role in the inheritance of genetic information. 12,13 The investigation of proton-bound base pairs in the gas phase offers a model system to deepen our understanding of base-pairing interactions at the molecular level, in which protonation is deeply involved. 2-4 Those observations led to a suggestion that the WC double helixes might also code for Hoogsteen base-pairing intrinsically, which offers a way of expanding the genetic information embedded in DNA structures beyond the capacity of WC base-pairing.

In fact, it is hydrogen bonding that directs the specific base-pairing between complementary nucleic acid bases.

…”

“…Due to the electrostatic interaction, the ionic hydrogen bonding offers a stronger interaction than neutral hydrogen bonding. 12,13 The investigation of proton-bound base pairs in the gas phase offers a model system to deepen our understanding of base-pairing interactions at the molecular level, in which protonation is deeply involved. 5,7,8 The mobile nature of the attached proton also causes intriguing anomalous behaviors in the dissociation of proton-bound base pairs by altering dissociation pathways, leading to the generation of isomeric fragments of proton-transferred products.…”

“…10 Likewise, the gas-phase conformations of proton-bound complexes of cytosine and guanine still requires further study, for which the present study compared the relative stabilities of proton-bound Hoogsteen and WC base pairs, i.e., the strengths of base-pairing interactions involved in the two conformations of [C:G:H] + along with its analogues: (1) the proton-bound base pairs of methylated C and G, i.e. 5 As for WC isomers, the proton is attached to the N7-position of guanine moieties, which is known to enhance the base-pairing interactions of WC base pairs of C and G. 12,13 The relative stabilities between the two conformations were compared by obtaining the energy differences in terms of ΔE 0 , ΔH, and ΔG (298.15 K), of which the results are given in Table 1. The B3LYP/6-311+G(2d,2p) theory was employed because it is known to be reliable in describing the base-pairing interaction involved in protonbound pairs of nucleic acid bases in comparison with ER-CID experiments in single and multiple collision conditions.…”