Theoretical Determination of One-Electron Oxidation Potentials for Nucleic Acid Bases

Abstract

The oxidation potentials for N-methyl substituted nucleic acid bases guanine, adenine, cytosine, thymine, uracil, xanthine, and 8-oxoguanine were computed using B3LYP and CBS-QB3 with the SMD solvation model. Acid-base and tautomeric equilibria present in aqueous solution were accounted for by combining standard redox potentials with calculated pKa and tautomerization energies to produce an ensemble averaged pH dependent potential. Gas phase free energies were computed using B3LYP/aug-cc-pVTZ//B3LYP/6-31+G(d,p) and CBS-QB3. Solvation free energies were computed at the SMD/B3LYP/6-31+G(d,p) level of theory. Compared to experimental results, calculations with the CBS-QB3 level of theory have a mean absolute error (MAE) of ca. 1 kcal/mol for the gas phase proton affinity/gas phase basicity and an MAE of ca. 0.04 eV for the adiabatic/vertical ionization potentials. The B3LYP calculations have a MAE of ∼2 kcal/mol for the proton affinity/gas phase basicity data but systematically underestimated ionization potentials by 0.14-0.21 eV. Solvent cavities for charged solute species were rescaled uniformly by fitting computed pKa data to experimentally measured pKa values. After solvent cavity scaling, the MAEs for computed pKa's compared to experimental results are 0.7 for B3LYP and 0.9 for CBS-QB3. In acetonitrile, the computed E°(XH(+•)/XH) redox potentials are systematically lower than experimentally measured potentials by 0.21 V for CBS-QB3 and 0.33 V for B3LYP. However, the redox potentials relative to adenine are in very good agreement with experimental results, with MAEs of 0.10 V for CBS-QB3 and 0.07 V for B3LYP. In aqueous solution, B3LYP and CBS-QB3 have MAEs of 0.21 and 0.19 V for E7(X(•),H(+)/XH). Replacing the methyl substituent with ribose changes the calculated E7 potentials by 0.1-0.2 V. The calculated difference between the guanine and adenine oxidation potentials is too large compared to experimental results, but the calculated difference between guanine and 8-oxoguanine is in good agreement with the measured values.

DFT study on the tautomerism of organic linker 1H-imidazole-4,5-tetrazole (HIT)

“…The acidity/basicity of a molecular site is important to the chemical and biological processes to know the preferred reactive site. Recent studies [67][68][69][70][71][72] have reported that pKa values calculated using DFT methods match well with experimental values. Hence in the present study, the pKa calculations were carried out for all the sixteen tautomeric forms (protonated) using the B3LYP/6-311++G(2d,2p) level of theory in both gas and liquid phases.…”

Computational Redox Potential Predictions: Applications to Inorganic and Organic Aqueous Complexes, and Complexes Adsorbed to Mineral Surfaces

“…One-electron oxidation potentials of these DNA bases were estimated computationally using DFT B3LYP and complete basis set (CBS-QB3) methods incorporating solvation effects using the solvation model density (SMD). However, both of these DFT and CBS-QB3 methods were found to underestimate the one electron oxidation potentials of nucleotide bases in acetonitrile solvent by MUEs of 0.33 and 0.21 eV, respectively [115]. Although the predicted oxidation potentials for these bases with respect to the SHE reference electrode, it should be noted that the absolute potential value used for the SHE was 4.28 eV as reported by Kelly et al, underestimated the experimental values by ~0.2-0.3 eV.…”

“…Interesting thing to note here is that the redox reaction of nucleic bases in aqueous solution would more likely to exhibit different tautomeric forms; this further complicates the redox potential prediction in aqueous solution. This problem was overcome by introducing ensemble redox potential, which is actually estimated based on the relative energies of the tautomers in the oxidized and reduced states [115].…”

DFT predictions of the oxidation potential of organic dyes for opto-electronic devices

“…(2) is usually determined by using a thermodynamic cycle (Fig. 2) in which the free energy of reaction (1) is separated into the sum of the gas-phase free energy and the difference of solvation free energy between the oxidized and reduced species [12,9]:…”

“…Several reports show that the widely used B3LYP functional is capable of predicting reliable ionization energies, for aromatic systems, even for difficult cases such as the oxidation of DNA nucleobases, nucleosides and oligonucleotides in solution [11][12][13][14][15][16][17][18]. However B3LYP was found to underestimate oxidation free energies of triphenylamine-based dipolar chromophores for dye-sensitized solar cells, while meta functionals furnished more accurate results [19].…”