9-methylguanine and 1-methylcytosine

We investigated the collision-induced dissociation (CID) reactions of a protonated Hoogsteen 9-methylguanine-1-methylcytosine base pair (HG-[9MG·1MC + H]+), which aims to address the mystery of the literature reported "anomaly" in product ion distributions and compare the kinetics of a Hoogsteen base pair with its Watson-Crick isomer WC-[9MG·1MC + H]+ (reported recently by Sun et al.; Phys. Chem. Chem. Phys., 2020, 22, 24986). Product ion cross sections and branching ratios were measured as a function of center-of-mass collision energy using guided-ion beam tandem mass spectrometry, from which base-pair dissociation energies were determined. Product structures and energetics were assessed using various theories, of which the composite DLPNO-CCSD(T)/aug-cc-pVTZ//ωB97XD/6-311++G(d,p) was adopted as the best-performing method for constructing a reaction potential energy surface. The statistical Rice-Ramsperger-Kassel-Marcus theory was found to provide a useful framework for rationalizing the dominating abundance of [1MC + H]+ over [9MG + H]+ in the fragment ions of HG-[9MG·1MC + H]+. The kinetics analysis proved the necessity for incorporating into kinetics modeling not only the static properties of reaction minima and transition states but more importantly, the kinetics of individual base-pair conformers that have formed in collisional activation. The analysis also pinpointed the origin of the statistical kinetics of HG-[9MG·1MC + H]+vs. the non-statistical behavior of WC-[9MG·1MC + H]+ in terms of their distinctively different intra-base-pair hydrogen-bonds and consequently the absence of proton transfer between the N1 position of 9MG and the N3' of 1MC in the Hoogsteen base pair. Finally, the Hoogsteen base pair was examined in the presence of a water ligand, i.e., HG-[9MG·1MC + H]+·H2O. Besides the same type of base-pair dissociation as detected in dry HG-[9MG·1MC + H]+, secondary methanol elimination was observed via the SN2 reaction of water with nucleobase methyl groups.

Topics: Base Pairing; Cytosine; Guanine; Kinetics; Molecular Conformation; Protons; Thermodynamics

A combined experimental and theoretical study is presented on the collision-induced dissociation (CID) of 9-methylguanine-1-methylcytosine base-pair radical cation (abbreviated as [9MG·1MC]˙+) and its monohydrate ([9MG·1MC]˙+·H2O) with Xe and Ar gases. Product ion mass spectra were measured as a function of collision energy using guided-ion beam tandem mass spectrometry, from which cross sections and threshold energies for various dissociation pathways were determined. Electronic structure calculations were performed at the DFT, RI-MP2 and DLPNO-CCSD(T) levels of theory to identify product structures and map out reaction potential energy surfaces. [9MG·1MC]˙+ has two structures: a conventional structure 9MG˙+·1MC (population 87%) consisting of hydrogen-bonded 9-methylguanine radical cation and neutral 1-methylcytosine, and a proton-transferred structure [9MG - H]˙·[1MC + H]+ (less stable, population 13%) formed by intra-base-pair proton transfer from the N1 of 9MG˙+ to the N3 of 1MC within 9MG˙+·1MC. The two structures have similar dissociation energies but can be distinguished in that 9MG˙+·1MC dissociates into 9MG˙+ and 1MC whereas [9MG - H]˙·[1MC + H]+ dissociates into neutral [9MG - H]˙ radical and protonated [1MC + H]+. An intriguing finding is that, in both Xe- and Ar-induced CID of [9MG·1MC]˙+, product ions were overwhelmingly dominated by [1MC + H]+, which is contrary to product distributions predicted using a statistical reaction model. Monohydration of [9MG·1MC]˙+ reversed the populations of the conventional structure (43%) vs. the proton-transferred structure (57%) and induced new reactions upon collisional activation, of which intra-base-pair hydrogen transfer produced [9MG + H]+ and the reaction of the water ligand with a methyl group in [9MG·1MC]˙+ led to methanol elimination from [9MG·1MC]˙+·H2O.

Topics: Base Pairing; Cytosine; Guanine; Hydrogen Bonding; Ligands; Protons; Water

A guided-ion beam tandem mass spectrometric study was performed on collision-induced dissociation (CID) of a protonated 9-methylguanine-1-methylcytosine Watson-Crick base pair (designated as WC-[9MG·1MC + H]

Topics: Base Pairing; Cations; Cytosine; Guanine; Protons

The transition structures (TS) between H-bonded (H) and stacked (S) structures of 9-methyladenine...1-methylthymine and 9-methylguanine...1-methylcytosine base pairs were localized at the DFT-D/TZVP potential energy surface. The energy barrier between the S and TS structures is considerably higher for the former pair than for the latter, which makes localization of the stacked structure of this pair possible.

Topics: Adenine; Base Pairing; Cytosine; Guanine; Hydrogen Bonding; Models, Molecular; Thermodynamics; Thymine

In this study, we present density functional theory calculations on the properties of proton transfer and electron binding in isolated, mono-, di-, and pentahydrated 9-methylguanine:1-methylcytosine (mG:mC) base pair radical anions. It was found that the proton transfer in mG:mC(*-) is coupled to the interbase propeller-twisting and stretching motions, which cooperatively shorten the proton-transfer distance. Without the propeller-twisting motion, the interbase stretching will be hindered and the proton-transfer distance will become somewhat longer, which in turn, results in rising of the kinetic barrier for proton transfer. The monohydration can assist or resist the proton-transfer reaction, depending on the hydration sites. Inclusion of five water molecules in the first hydration shell around mG:mC(*-) only moderately lowers the proton-transfer barrier from 3.80 to 3.01 kcal mol(-1) and the reaction energy from -3.16 to -6.40 kcal mol(-1) due to the cancellation between opposite influences of H(2)O molecules. A further consideration of bulk hydration using a polarizable continuum model does not affect the proton-transfer energetics. In contrast, both the first hydration shell and bulk hydration were found to play important roles in stabilizing the excess electron in mG:mC; the adiabatic electron affinity of mG:mC increases from 0.302 to 0.645 eV upon inclusion of five water molecules in the first hydration shell, and further increases to 1.813 eV when the bulk hydration is considered. We noticed that the water molecule can enhance electron binding by direct interaction with the nucleobase that accommodates excess electron or through the indirect effect of tuning interbase hydrogen bonds. In addition, the microhydration effects on proton transfer and electron binding were found to be approximately additive.

Topics: Base Pairing; Cytosine; Electrons; Free Radicals; Guanine; Protons; Quantum Theory; Water

Monohydration structures of the guanine-guanine and guanine-cytosine base pairs have been elucidated by IR-UV double resonance spectroscopy combined with ab initio calculations. The systems studied consist of the homodimer of 9-methylguanine and the heterodimer of 9-methylguanine and 1-methylcytosine in which the methyl group is introduced to mimic the presence of the sugar-phosphate backbone and to block specific tautomerization. The monohydrate of the homodimer is identified as that of the most stable symmetric structure formed by the keto tautomers of guanine, which demonstrates that the base pair structure is not influenced by the hydration. It is also shown that at least two structural isomers, one of which retains the Watson-Crick GC pair structure, contribute the monohydrated cluster of the heterodimer. Although stacked base pairs are suggested to be significantly stabilized by the addition of water, the result shows no clear indication for the presence of stacked monohydrates in either homodimer or heterodimer case.

Topics: Base Pairing; Cytosine; Guanine; Molecular Dynamics Simulation

The photoelectron spectrum for the radical anion of 9-methylguanine-1-methylcytosine, MGMC(-), was recorded for the first time. To interpret the experimental results, B3LYP/6-31++G(d,p) level computational studies were carried out for the neutral and anionic complexes of MGMC/MGMC(-) stabilized by three hydrogen bonds and comprising canonical or low-energy tautomeric forms of the methylated nucleobases. The visualization of singly occupied molecular orbitals for the MGMC(-) anions indicates that they are valence-bound species since the excess electron is localized on a pi* orbital of cytosine. All but one of the studied anionic complexes are adiabatically stable at the applied B3LYP level of theory. The intensity maximum of the broad band in the photoelectron spectrum was measured at 2.1 eV. This value is very well reproduced by the calculated vertical detachment energy of the calculated global minimum geometry of the MGMC(-) anion. This structure is the Watson-Crick base pair anion with proton transferred from the N1 atom of guanine to the N3 site of cytosine. The calculated adiabatic electron affinities span a range of 0.39-0.60 eV. The consequences of electron attachment to the AT or GC base pairs incorporated within DNA are briefly discussed in the context of DNA damage by low-energy electrons.

Topics: Anions; Cytosine; DNA; Guanine; Hydrogen Bonding; Models, Molecular; Molecular Conformation; Nucleic Acid Conformation; Spectrum Analysis; Thermodynamics

The addition of 1-methylcytosine (1-MeCy) or 9-methylguanine (9-MeGu) to solutions of cis-(PPh3)2P(ONO2)2 (1a), in a molar ratio of 1:1, affords the monoadducts cis-[(PPh3)2Pt(1-MeCy)(ONO2)]NO3 (2a) and cis-[(PPh3)2Pt(9-MeGu)(ONO2)]NO3 (3a) and only trace amounts of the bisadducts cis-[(PPh3)2Pt(1-MeCy)2](NO3)2 (4a) and cis-[(PPh3)2Pt(9-MeGu)2](NO3)2 (5a), respectively. The X-ray structural determination of 2a and 3a indicates a strong pi-pi stacking interaction between one of the PPh3 phenyl groups and the pyrimydinic N3-platinated cytosine or the imidazole part of the N7-coordinated guanine base. The addition of a further equiv of nucleobase to the monoadducts forms quantitatively the bisadducts that have been isolated as pure compounds 4a and 5a. Under the same experimental conditions, the dinitrato analogue cis-[(PMePh2)2Pt(ONO2)2] (1b) forms the monoadducts 2b and 3b in equilibrium with a relatively high concentration (20-30%) of the bisadducts cis-[(PMePh2)2Pt(1-MeCy)2](NO3)2 (4b) and cis-[(PMePh2)2Pt(9-MeGu)2](NO3)2 (5b), which have been structurally characterized by single-crystal X-ray analysis. The characterization of the isolated complexes by multinuclear NMR spectroscopy is also described.

Topics: Crystallography, X-Ray; Cytosine; Guanine; Ligands; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Phosphines; Platinum Compounds

Planar H-bonded and stacked structures of guanine...cytosine (G.C), adenine...thymine (A...T), 9-methylguanine...1-methylcytosine (mG...mC), and 9-methyladenine...1-methylthymine (mA...mT) were optimized at the RI-MP2 level using the TZVPP ([5s3p2d1f/3s2p1d]) basis set. Planar H-bonded structures of G...C, mG...mC, and A...T correspond to the Watson-Crick (WC) arrangement, in contrast to mA...mT for which the Hoogsteen (H) structure is found. Stabilization energies for all structures were determined as the sum of the complete basis set limit of MP2 energies and a (DeltaE(CCSD(T)) - DeltaE(MP2)) correction term evaluated with the cc-pVDZ(0.25,0.15) basis set. The complete basis set limit of MP2 energies was determined by two-point extrapolation using the aug-cc-pVXZ basis sets for X = D and T and X = T and Q. This procedure is required since the convergency of the MP2 interaction energy for the present complexes is rather slow, and it is thus important to include the extrapolation to the complete basis set limit. For the MP2/aug-cc-pVQZ level of theory, stabilization energies for all complexes studied are already very close to the complete basis set limit. The much cheaper D-->T extrapolation provided a complete basis set limit close (by less than 0.7 kcal/mol) to the more accurate T-->Q term, and the D-->T extrapolation can be recommended for evaluation of complete basis set limits of more extended complexes (e.g. larger motifs of DNA). The convergency of the (DeltaE(CCSD(T)) - DeltaE(MP2)) term is known to be faster than that of the MP2 or CCSD(T) correlation energy itself, and the cc-pVDZ(0.25,0.15) basis set provides reasonable values for planar H-bonded as well as stacked structures. Inclusion of the CCSD(T) correction is essential for obtaining reliable relative values for planar H-bonding and stacking interactions; neglecting the CCSD(T) correction results in very considerable errors between 2.5 and 3.4 kcal/mol. Final stabilization energies (kcal/mol) for the base pairs studied are very substantial (A...T WC, 15.4; mA...mT H, 16.3; A...T stacked, 11.6; mA...mT stacked, 13.1; G...C WC, 28.8; mG...mC WC, 28.5; G...C stacked, 16.9; mG...mC stacked, 18.0), much larger than published previously. On the basis of comparison with experimental data, we conclude that our values represent the lower boundary of the true stabilization energies. On the basis of error analysis, we expect the present H-bonding energies to be fairly close to the true values, while

Topics: Adenine; Base Pairing; Cytosine; Guanine; Hydrogen Bonding; Models, Chemical; Models, Molecular; Thermodynamics; Thymine

The substitution effect on hydrogen bond stability of the Watson-Crick type base pair between 1-methylcytosine (C) and substitution-introduced 9-methylguanine derivatives (Gx) was studied by an ab initio molecular orbital theory. Introduction of an electron-withdrawing group on the 8-position or on the exo-cyclic amino moiety enforced the base pair stability.

Topics: Cytosine; Guanine; Hydrogen Bonding; Thermodynamics

The substitution effect on hydrogen bond energy of the Watson-Crick type base pair between 9-methylguanine (G) and chemically modified 1-methylcytosine (CX) derivatives was evaluated by ab initio molecular orbital theory. A remarkable trend was observed in the substitution effect of the hydrogen bond stability: Cytosine derivatives possessing an electron-donating group form stable base pairs with guanine. However, both the hydrogen bond distance and the charge distribution were not good indexes for the hydrogen bond status in CX-G base pairing.

Topics: Base Pairing; Cytosine; Guanine; Hydrogen Bonding

Normal modes analyses for different molecules with biological interest have been performed and checked via the calculation of resonance Raman intensities. For this purpose, molecular orbital calculations were used to determine bond order changes in the lowest-lying electronic transitions. These bond order changes were used to calculate resonance Raman intensities in order to obtain correct vibrational assignments and reliable force fields.

Topics: Amino Acids; Base Pairing; Cresols; Cytosine; Electromagnetic Fields; Electrons; Guanine; Hydrocarbons, Aromatic; Imidazoles; Indoles; Molecular Structure; Nucleic Acids; Quantum Theory; Spectrum Analysis, Raman; Statistics as Topic; Thymine; Ultraviolet Rays; Uracil