Study of 7-Methylguanine on pK_aValues by Using Density Functional Theoretical Method

Abstract

Methylation of DNA by endogenous methylating agents generates a variety of genotoxic adducts.1 The N7 position of guanine is known as the most nucleophilic site within the heterocyclic bases of DNA.2 Accordingly, N7-methylguanine (7MeG) is the one of the most prevailing forms of the methylated guanine. 7MeG is also generated by methylation in order to be used as a probe of protein-DNA interactions and DNA sequencing. Recently, a DNA double helical structure of a 25-mer containing a 7MeG was reported, which revealed the base pairing characteristics of 7MeG.1 Information on the acid dissociation constants and the relative populations of various tautomers would provide valuable clues toward optimizing analysis of 7MeG and to understand the biological consequences of the modified base.We have developed a scheme based on density-functional theoretical calculations in combination with the Poisson-Boltzmann continuum solvation model for water to predict pKa values and the major tautomeric forms of a number of nucleobases, their oxidative damage products, 3-5 and heteronuclear aromatic compounds. 6,7 As well as macroscopic pKa values, we reproduced the micro pKa values of individual protonation sites of purine nucleobases.8 Hydrogen transfer between paired nucleobases was also investigated using the same computational model. Among methylated guanine species, we have already reported computations on the tautomerism and pK a values of 9-methylguanine (9MeG) and 7,9-dimethylguanine.8 Gas-phase vibrational experiments and computation results on 1,7-dimethylguanine, 7MeG, and 9MeG were also reported. 10In the current work, we report calculated relative stabilities of the tautomers of 7MeG at each ionization stage and the pKa values of 7MeG in aqueous solution.pKa calculations on the nucleobases and their derivatives are complicated due to the presence of multiple tautomers with different site-specific microscopic pKa values. A way to estimate the overall macroscopic pKa from the site-specific pKa's of the tautomers devised in our previous studies and the details of the computation scheme have been presented elsewhere. 3,4For a deprotonation process leading the i-th tautomer of an acid HA into the j-th tautomer of the conjugate base A -, the Gibbs energy of deprotonation reaction is calculated as (1) and the corresponding micro pKa ij values is given bywhere R is the gas constant and T is 298.15 K. From this micro pK a ij value, the partial population of the i-th tautomer out of all of the acid species ( fi), and the partial population of the j-th tautomer out of all of the conjugate base species ( fj ' ), the macro pKa value is estimated as 4 pKa = pKa ij -log fi + log fj ' .The standard free energy of each species (HA, A -, and H + ) in water, ∆Ga 0 q, can be written as the sum of the gas-phase standard Gibbs energy ∆Gg 0 and the standard Gibbs energy of solvation in water ∆Gs 0 olv:The standard Gibbs energy of each species in the gas phase, ∆Gg 0 , is obtained byThe total energy of the molecule at 0 K (E0 K) is calculated ...

Voltammetric Behaviour of 7‐Methylguanine Using Screen‐printed Graphite Electrodes: towards a Guanine Methylation Electrochemical Sensor

“…Moreover, 7mG has two macroscopic pKa values: the first pKa value is 4.44 and the second one is 10.75 according to Hwang et al. 35. We have found a slope change at the plot peak potential versus pH at a pH value below 4.0, as depicted in figure S3.…”

Boron-doped diamond electrodes explored for the electroanalytical detection of 7-methylguanine and applied for its sensing within urine samples

“…This indicates that an equal amount of protons and electrons is involved in electrode reaction as well. However, it is worth noting that at pH 4.19, SWV response deviates from the linear trend attributed to the pKa1 of the substance near 4.4 [49]. By contrast, Brotons et al [27] reported a value of pH dependence for the electro-oxidation of 7-mG at screen printed graphite electrodes (SPGE) of 27 mV pH -1 within a pH range of 3 and 9 in phosphate buffer solutions.…”